Tofacitinib, an oral Janus kinase inhibitor, in patients from Colombia with rheumatoid arthritis: Pooled efficacy and safety analyses of data from phase III studies | Revista Colombiana de Reumatología (English Edition)

array:23 ["pii" => "S2444440519300329" "issn" => "24444405" "doi" => "10.1016/j.rcreue.2018.08.002" "estado" => "S300" "fechaPublicacion" => "2018-10-01" "aid" => "199" "copyright" => "The Author(s)" "copyrightAnyo" => "2018" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Rev Colomb Reumatol. 2018;25:233-44" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 213 "formatos" => array:3 [ "EPUB" => 32 "HTML" => 122 "PDF" => 59 ] ] "itemSiguiente" => array:19 [ "pii" => "S2444440519300354" "issn" => "24444405" "doi" => "10.1016/j.rcreue.2018.08.003" "estado" => "S300" "fechaPublicacion" => "2018-10-01" "aid" => "200" "copyright" => "Asociación Colombiana de Reumatología" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Rev Colomb Reumatol. 2018;25:245-56" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 509 "formatos" => array:3 [ "EPUB" => 38 "HTML" => 353 "PDF" => 118 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "Original Investigation" "titulo" => "Prevalence of rheumatic disease in Colombia according to the Colombian Rheumatology Association (COPCORD) strategy. Prevalence study of rheumatic disease in Colombian population older than 18 years" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "245" "paginaFinal" => "256" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Prevalencia de la enfermedad reumática en Colombia, según estrategia COPCORD-Asociación Colombiana de Reumatología. Estudio de prevalencia de enfermedad reumática en población colombiana mayor de 18 años" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0025" "etiqueta" => "Fig. 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 2857 "Ancho" => 2395 "Tamanyo" => 327773 ] ] "descripcion" => array:1 [ "en" => "Quality of life and functional limitation assessed by EQ-5D-3L and HAQ-DI. Panel A: Functional ability assessed by HAQ, the dots represent the mean of the instrument. Panel B: The lines represent the percentage of patients without pain of discomfort, anxiety or depression, or without mobility problems to perform daily living activities or personal care. RA: rheumatoid arthritis; CHIKV: chikungunya fever; FM: fibromyalgia; SLE: systemic lupus erythematosus; MLBP: mechanical low back pain; OA: osteoarthritis; OTHER: other non-rheumatic diseases; RRPS: regional appendicular pain syndrome; HEALTHY: healthy individuals; SpA: spondyloarthritis." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "John Londoño, Ingris Peláez Ballestas, Francy Cuervo, Ignacio Angarita, Rodrigo Giraldo, Juan Camilo Rueda, Jesús Giovanny Ballesteros, Roberto Baquero, Elías Forero, Mario Cardiel, Eugenia Saldarriaga, Andrés Vásquez, Sofía Arias, Lina Valero, Camilo González, Javier Ramírez, Carlos Toro, Ana María Santos" "autores" => array:18 [ 0 => array:2 [ "nombre" => "John" "apellidos" => "Londoño" ] 1 => array:2 [ "nombre" => "Ingris" "apellidos" => "Peláez Ballestas" ] 2 => array:2 [ "nombre" => "Francy" "apellidos" => "Cuervo" ] 3 => array:2 [ "nombre" => "Ignacio" "apellidos" => "Angarita" ] 4 => array:2 [ "nombre" => "Rodrigo" "apellidos" => "Giraldo" ] 5 => array:2 [ "nombre" => "Juan Camilo" "apellidos" => "Rueda" ] 6 => array:2 [ "nombre" => "Jesús Giovanny" "apellidos" => "Ballesteros" ] 7 => array:2 [ "nombre" => "Roberto" "apellidos" => "Baquero" ] 8 => array:2 [ "nombre" => "Elías" "apellidos" => "Forero" ] 9 => array:2 [ "nombre" => "Mario" "apellidos" => "Cardiel" ] 10 => array:2 [ "nombre" => "Eugenia" "apellidos" => "Saldarriaga" ] 11 => array:2 [ "nombre" => "Andrés" "apellidos" => "Vásquez" ] 12 => array:2 [ "nombre" => "Sofía" "apellidos" => "Arias" ] 13 => array:2 [ "nombre" => "Lina" "apellidos" => "Valero" ] 14 => array:2 [ "nombre" => "Camilo" "apellidos" => "González" ] 15 => array:2 [ "nombre" => "Javier" "apellidos" => "Ramírez" ] 16 => array:2 [ "nombre" => "Carlos" "apellidos" => "Toro" ] 17 => array:2 [ "nombre" => "Ana María" "apellidos" => "Santos" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0121812318300951" "doi" => "10.1016/j.rcreu.2018.08.003" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0121812318300951?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2444440519300354?idApp=UINPBA00004N" "url" => "/24444405/0000002500000004/v1_201905160826/S2444440519300354/v1_201905160826/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S2444440519300287" "issn" => "24444405" "doi" => "10.1016/j.rcreue.2019.04.003" "estado" => "S300" "fechaPublicacion" => "2018-10-01" "aid" => "193" "copyright" => "Asociación Colombiana de Reumatología" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Rev Colomb Reumatol. 2018;25:228-32" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 239 "formatos" => array:3 [ "EPUB" => 37 "HTML" => 127 "PDF" => 75 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "Original Investigation" "titulo" => "Literature analysis of economic aspects of rheumatoid arthritis" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "228" "paginaFinal" => "232" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Análisis bibliométrico de temas económicos en artritis reumatoide" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1212 "Ancho" => 1508 "Tamanyo" => 116525 ] ] "descripcion" => array:1 [ "en" => "Distribution of countries of origin of the identified articles." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Melany Santrich Sotomayor, María Eugenia Casanova, José Mauricio Ocampo" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Melany" "apellidos" => "Santrich Sotomayor" ] 1 => array:2 [ "nombre" => "María Eugenia" "apellidos" => "Casanova" ] 2 => array:2 [ "nombre" => "José Mauricio" "apellidos" => "Ocampo" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0121812318300884" "doi" => "10.1016/j.rcreu.2018.07.003" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0121812318300884?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2444440519300287?idApp=UINPBA00004N" "url" => "/24444405/0000002500000004/v1_201905160826/S2444440519300287/v1_201905160826/en/main.assets" ] "en" => array:22 [ "idiomaDefecto" => true "cabecera" => "Original Investigation" "titulo" => "Tofacitinib, an oral Janus kinase inhibitor, in patients from Colombia with rheumatoid arthritis: Pooled efficacy and safety analyses of data from phase III studies" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "233" "paginaFinal" => "244" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Patricia Vélez, Juan J. Jaller, William J. Otero Escalante, Erika G. García, Ricardo Rojo, Douglass Chapman, Katherine Persand, Giovanna A. Matiz" "autores" => array:8 [ 0 => array:3 [ "nombre" => "Patricia" "apellidos" => "Vélez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 1 => array:3 [ "nombre" => "Juan J." "apellidos" => "Jaller" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "William J." "apellidos" => "Otero Escalante" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "Erika G." "apellidos" => "García" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "d" "identificador" => "aff0020" ] 1 => array:2 [ "etiqueta" => "1" "identificador" => "fn0005" ] ] ] 4 => array:3 [ "nombre" => "Ricardo" "apellidos" => "Rojo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "e" "identificador" => "aff0025" ] ] ] 5 => array:3 [ "nombre" => "Douglass" "apellidos" => "Chapman" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "f" "identificador" => "aff0030" ] ] ] 6 => array:3 [ "nombre" => "Katherine" "apellidos" => "Persand" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "g" "identificador" => "aff0035" ] 1 => array:2 [ "etiqueta" => "1" "identificador" => "fn0005" ] ] ] 7 => array:4 [ "nombre" => "Giovanna A." "apellidos" => "Matiz" "email" => array:1 [ 0 => "Giovannaalexandra.matiz@pfizer.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "g" "identificador" => "aff0035" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:7 [ 0 => array:3 [ "entidad" => "Reumatología, CIREI SAS, Bogotá, Colombia" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Centro de Reumatología y Ortopedia, Barranquilla, Colombia" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Departamento de Medicina Interna, Facultad de Salud, Universidad Industrial de Santander, Centro de Investigación Clínica Servimed E.U., Bucaramanga, Colombia" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Pfizer Inc, Collegeville, PA, USA" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Pfizer Inc, Groton, CT, USA" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Pfizer Inc, New York, NY, USA" "etiqueta" => "f" "identificador" => "aff0030" ] 6 => array:3 [ "entidad" => "Pfizer Colombia, Bogotá, Colombia" "etiqueta" => "g" "identificador" => "aff0035" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Tofacitinib, un inhibidor oral de la janus kinasa, en pacientes colombianos con artritis reumatoide: análisis de eficacia y seguridad de los estudios de fase III" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1365 "Ancho" => 2493 "Tamanyo" => 121279 ] ] "descripcion" => array:1 [ "en" => "Mean (SE) DAS28-4(ESR) over time for the tofacitinib 5 and 10mg BID groups in the efficacy subpopulation (FAS, observed). BID: twice daily; DAS28-4(ESR): Disease Activity Score-erythrocyte sedimentation rate; FAS: full analysis set; SE: standard error. N represents the numbers of patients with non-missing DAS28-4(ESR). Efficacy analyses were based on three studies: ORAL Scan, ORAL Solo and ORAL Sync." ] ] ] "textoCompleto" => "IntroductionRheumatoid arthritis (RA) is a debilitating autoimmune disease that leads to chronic inflammation and destruction of the joints and surrounding tissues of the musculoskeletal system. Conservative estimates suggest that the prevalence rates for RA in the Latin American population (as a whole) range from 0.4% to 1.6%.<a class="elsevierStyleCrossRef" href="#bib0275">1</a> A recent review of the epidemiology of RA in Colombia used medical records data to estimate the disease prevalence in Colombia to be 0.15%,<a class="elsevierStyleCrossRef" href="#bib0280">2</a> and an analysis of RA prevalence specifically for African Colombians from Quibdo observed a period prevalence rate of 0.01%.<a class="elsevierStyleCrossRef" href="#bib0285">3</a> However, a report from 2005 administrative sources estimated an overall Colombian prevalence of 0.9%.<a class="elsevierStyleCrossRef" href="#bib0290">4</a> These low and varying prevalence rates may be due to genetic factors, under-diagnosis and reduced access to treatment.Consistent with European and US guidelines,<a class="elsevierStyleCrossRefs" href="#bib0295">5,6</a> Latin American specific guidelines (Pan-American League of Associations for Rheumatology [PANLAR] and Grupo Latinoamericano de Estudio de Artritis Reumatoide [GLADAR]) state that RA treatment should control inflammation, minimize joint destruction and radiographic progression, preserve functional and work capabilities and improve quality of life.<a class="elsevierStyleCrossRef" href="#bib0305">7</a> However, clinical management of RA in Latin American countries is subject to several challenges. For example, patient referral to specialist rheumatologists may be restricted or delayed, access to cost-effective medication, medical resources and public health services may be limited, and there is a lack of public policies and education surrounding RA.<a class="elsevierStyleCrossRefs" href="#bib0275">1,7–10</a> Early diagnosis and treatment is important for slowing the structural progression of RA<a class="elsevierStyleCrossRef" href="#bib0325">11</a>; however, in a survey of Colombian rheumatologists, 48.6% of respondents considered early RA to represent the first 3 months after onset of symptoms, yet 54.5% believed that patients were not referred to specialists until between 3 and 6 months after symptom onset.<a class="elsevierStyleCrossRef" href="#bib0330">12</a>For patients with RA in Colombia, first-line treatment generally consists of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), followed by biologic disease-modifying antirheumatic drugs (bDMARDs), such as tumor necrosis factor inhibitors, for patients who do not show an adequate response to initial treatment.<a class="elsevierStyleCrossRefs" href="#bib0335">13–16</a> Screening for latent TB prior to initiation of bDMARDs is recommended in Latin American guidelines.<a class="elsevierStyleCrossRef" href="#bib0305">7</a> As the incidence of Mycobacterium tuberculosis (TB) in Colombia is intermediate at 31 (range 24–39) cases per 100,000 population; both screening and monitoring for occurrence of TB during treatment is important in the Colombian patient population.<a class="elsevierStyleCrossRef" href="#bib0355">17</a> In Colombia, tofacitinib is recommended in adult patients with RA after failure to csDMARDs or biologic therapy.<a class="elsevierStyleCrossRef" href="#bib0350">16</a>Although bDMARDs have not previously been commonly prescribed in Colombia,<a class="elsevierStyleCrossRefs" href="#bib0280">2,12</a> a recent retrospective study has shown an increasing number of prescriptions for bDMARDs among the study cohort of patients with RA, with more than one-quarter receiving bDMARDs by the end of the study, with etanercept and abatacept the most frequently used.<a class="elsevierStyleCrossRef" href="#bib0345">15</a> In the Colombian patient population, infliximab and adalimumab have previously been shown to improve functional capacity and quality of life in patients with refractory RA.<a class="elsevierStyleCrossRefs" href="#bib0360">18,19</a> However, traditionally, the low prescription of bDMARDs may be a consequence of the high costs associated with bDMARDs, and the requirement for close clinical and serologic monitoring of patients. A recent Colombian cross-sectional study showed that from one-third to half of patients attending a specialized care clinic were in remission according to disease activity score (DAS28 <2.6; DAS erythrocyte sedimentation rate [ESR] 34.1% and DAS28 C-reactive protein [CRP] 49.5%),<a class="elsevierStyleCrossRef" href="#bib0335">13</a> although it is important to note that acute phase reactant levels may not always reflect disease activity.<a class="elsevierStyleCrossRef" href="#bib0370">20</a> A Colombian retrospective cohort analysis showed 42.9% of patients achieving remission defined as DAS28 ≤2.6,<a class="elsevierStyleCrossRef" href="#bib0345">15</a> highlighting a requirement for alternative RA therapies. Moreover, although this remission rate may seem high, remission rates using different parameters, such as Routine Assessment of Patient Index Data (RAPID), Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), often show lower remission rates.<a class="elsevierStyleCrossRefs" href="#bib0375">21,22</a>Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. The efficacy and safety of tofacitinib 5 and 10mg twice daily (BID) have been demonstrated in patients with moderately to severely active RA and various treatment histories in randomized global phase II<a class="elsevierStyleCrossRefs" href="#bib0385">23–28</a> and phase III<a class="elsevierStyleCrossRefs" href="#bib0415">29–34</a> studies of up to 24 months’ duration, and in long-term extension (LTE) studies with up to 114 months of observation.<a class="elsevierStyleCrossRefs" href="#bib0445">35–37</a> Safety and efficacy of tofacitinib specifically in Latin American populations have been analyzed previously in Phase III and LTE studies, due to differences in epidemiology and treatment guidelines compared with global populations. <a class="elsevierStyleCrossRefs" href="#bib0460">38,39</a> In this post hoc analysis, the efficacy and safety of tofacitinib 5 and 10mg BID was evaluated in a subpopulation of Colombian patients included in the global phase III studies in RA.MethodsPatientsThis analysis included data from Colombian patients enrolled in four global phase III studies of tofacitinib for the treatment of RA. Patient inclusion and exclusion criteria have previously been reported in detail for each individual study.<a class="elsevierStyleCrossRefs" href="#bib0350">16,29–31,33</a> In summary, eligible patients were aged ≥18 years and had a diagnosis of moderately to severely active RA based on American College of Rheumatology (ACR) 20/50/70 response rate criteria.<a class="elsevierStyleCrossRef" href="#bib0470">40</a> Patients were excluded if they had recent, current or serious chronic infections; active or inadequately treated latent TB infection; history of recurrent herpes zoster, disseminated herpes zoster, or disseminated herpes simplex; hepatitis B or C; human immunodeficiency virus; evidence or history of malignancy, other than adequately treated or excised non-metastatic basal or squamous cell cancer of the skin, or cervical carcinoma in situ; and evidence or history of lymphoma or lymphoproliferative disease.Study designsData were analyzed from four phase III double-blind, randomized, controlled studies of 6–24 months’ duration that included patients from Colombia: ORAL Sync [<a href="ctgov:NCT00856544">NCT00856544</a>; 12 months],<a class="elsevierStyleCrossRef" href="#bib0420">30</a> ORAL Scan [<a href="ctgov:NCT00847613">NCT00847613</a>; 24 months],<a class="elsevierStyleCrossRef" href="#bib0425">31</a> ORAL Solo [<a href="ctgov:NCT00814307">NCT00814307</a>; 6 months]<a class="elsevierStyleCrossRef" href="#bib0415">29</a> and ORAL Start [<a href="ctgov:NCT01039688">NCT01039688</a>; 12-month data-cut, study was ongoing, database not locked].<a class="elsevierStyleCrossRef" href="#bib0435">33</a> These studies included patients who had previously had an inadequate response to methotrexate (ORAL Scan), or ≥1 bDMARD or csDMARD (ORAL Sync and ORAL Solo). Patients enrolled in ORAL Start were naïve to methotrexate treatment (defined as no prior treatment or ≤3 weekly doses). In ORAL Scan, ORAL Sync and ORAL Solo, patients were randomized to receive tofacitinib 5mg BID, tofacitinib 10mg BID, placebo advanced to tofacitinib 5mg BID, or placebo advanced to tofacitinib 10mg BID. In the ORAL Sync and ORAL Scan studies, placebo patients who did not achieve ACR20 at Month 3 were advanced to tofacitinib treatment according to randomization. All remaining placebo patients advanced to tofacitinib treatment at Month 6. All placebo patients advanced to tofacitinib treatment at Month 3 in ORAL Solo. In ORAL Start, patients were randomized to receive tofacitinib 5mg BID, tofacitinib 10mg BID, or methotrexate 10mg per week titrated to 20mg per week over the course of 8 weeks, and maintained for the duration of the study. Study drug was administered either as monotherapy (in ORAL Solo and ORAL Start), or in combination with background methotrexate (ORAL Scan) or csDMARDs (ORAL Sync). Further information on study initiation, completion dates and Principal Investigators is shown in <a class="elsevierStyleCrossRef" href="#sec0090">Supplementary Table 4</a>.All studies were conducted in accordance with the Declaration of Helsinki and the International Conference on Harmonisation Good Clinical Practice Guidelines, and were approved by Institutional Review Boards and/or Independent Ethics Committees at each of the investigational centers participating in the study. All patients provided written informed consent.Efficacy endpointsEfficacy endpoints assessed up to Month 24 included: ACR20, ACR50 and ACR70 response rates; mean Disease Activity Score (DAS)28-4 (erythrocyte sedimentation rate [ESR]) scores; and mean change from baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) scores.Safety endpointsEndpoints included reporting of adverse events (AEs), serious AEs, discontinuations due to AEs, and mortality cases. Malignancy events were adjudicated by an independent adjudication committee, which carried out a blinded review of each biopsy case with at least two independent, board-certified pathologists. Major cardiovascular AEs and all deaths were adjudicated by a blinded, independent, external cardiovascular safety endpoint adjudication committee for all phase III studies. Patients were screened for latent or untreated TB before enrollment, in accordance with the protocol for patients using bDMARDs in other Latin American countries.<a class="elsevierStyleCrossRefs" href="#bib0475">41,42</a> All available safety data were analyzed up to Month 24.Statistical analysisAll efficacy and safety analyses were based on observed cases (i.e. no imputation of missing values) in the full analysis set (FAS), which included all patients who were randomized and received at least one dose of study treatment (tofacitinib, placebo or methotrexate). Efficacy analyses were assessed using FAS pooled data from three studies (ORAL Scan, ORAL Solo and ORAL Sync). Patients from ORAL Start were not included in efficacy analyses as they were a methotrexate-naïve population, and therefore represented a different patient population versus the populations in the other three studies. Efficacy data are reported for tofacitinib groups only, as patient numbers in the placebo and methotrexate groups were too low for meaningful comparison. Safety analyses were performed on FAS data pooled from all four studies (ORAL Scan, ORAL Solo, ORAL Sync and ORAL Start). Despite low patient numbers in some groups, safety data are reported for all groups for completeness. All analyses were descriptive in nature, and general trends were described. Due to small sample sizes, no statistical hypothesis testing was performed; therefore, all differences described in the Results section refer to numerical differences only.ResultsPatientsIn total, 77 Colombian patients from three studies (ORAL Scan, ORAL Solo and ORAL Sync) were included in the efficacy analysis, and 125 Colombian patients from four studies (ORAL Scan, ORAL Solo, ORAL Sync and ORAL Start) were included in the safety analyses. Baseline demographics and characteristics were generally similar across treatment groups within the efficacy and safety analyses populations, although in the safety population the mean duration of RA was higher in the placebo groups and both the mean duration of RA and mean age were lower in the methotrexate-treated groups versus the other treatment groups (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>EfficacyAt Month 1, ACR20 response rates for both tofacitinib 5mg BID (75.0%) and tofacitinib 10mg BID (74.2%) were similar. Between Month 3 and Month 9, ACR20 responses ranged from 66.7–to 74.2% and 76.7–86.2% for tofacitinib 5 and 10mg BID, respectively (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A and <a class="elsevierStyleCrossRef" href="#sec0090">Supplementary Table 1</a>). By Month 12, ACR20 response rates for both tofacitinib 5 and 10mg BID groups improved further (82.4% and 93.8%, respectively). Therefore, although patient numbers reduced after Month 6, ACR20 response rates across all treatment groups were generally sustained to Month 12 (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A and <a class="elsevierStyleCrossRef" href="#sec0090">Supplementary Table 1</a>). After Month 12, patient numbers were low; however, improvements in ACR20 responses appeared to be generally sustained through Month 24 (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A and <a class="elsevierStyleCrossRef" href="#sec0090">Supplementary Table 1</a>).<elsevierMultimedia ident="fig0005"></elsevierMultimedia>ACR50 response improved over time for both tofacitinib 5 and 10mg BID groups from Month 1 (21.9% and 41.9%, respectively), and from Month 3 (48.5% and 53.3%, respectively) through to Month 12 (52.9% and 75.0%, respectively) (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B and <a class="elsevierStyleCrossRef" href="#sec0090">Supplementary Table 1</a>). Tofacitinib 10mg BID appeared to show higher ACR50 responses than tofacitinib 5mg BID, although no formal statistical analysis was performed. From Month 12 to Month 24, patient numbers were low for both tofacitinib 5 and 10mg BID groups, and ACR50 responses ranged from 33.3–83.3% and 66.7–83.3%, respectively (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B and <a class="elsevierStyleCrossRef" href="#sec0090">SupplementaryTable 1</a>).Similarly, ACR70 response rates improved over time for both tofacitinib 5 and 10mg BID groups from Month 1 (3.1% and 9.7%, respectively), and from Month 3 (21.2% and 20.0%, respectively) through to Month 12 (41.2% and 43.8%, respectively) (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>C and <a class="elsevierStyleCrossRef" href="#sec0090">Supplementary Table 1</a>). ACR70 responses were comparable among both tofacitinib groups from Month 3 to Month 12. From Month 12 to Month 24, ACR70 responses varied over time with tofacitinib 5mg BID (0–50.0%), and were generally sustained with tofacitinib 10mg BID (28.6–44.4%); however, patient numbers for these time points were low (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>C and <a class="elsevierStyleCrossRef" href="#sec0090">Supplementary Table 1</a>).Mean DAS28-4(ESR) steadily improved over time for both tofacitinib 5 and 10mg BID groups from baseline (6.3 and 6.2, respectively), to Month 1 (4.6 and 4.0, respectively), to Month 3 (4.3 and 3.9, respectively) and through to Month 12 (3.7 and 2.8, respectively) (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a> and <a class="elsevierStyleCrossRef" href="#sec0090">Supplementary Table 2</a>). Although patient numbers were low after Month 12, improvements in mean DAS28-4(ESR) appeared to be generally sustained through to Month 24 (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a> and <a class="elsevierStyleCrossRef" href="#sec0090">Supplementary Table 2</a>).<elsevierMultimedia ident="fig0010"></elsevierMultimedia>Improvements from baseline in mean HAQ-DI scores were observed for both tofacitinib 5 and 10mg BID groups as early as Month 1 (−0.4 and −0.9, respectively), and were sustained over time to Month 3 (−0.6 and −0.9) through to Month 12 (−1.0 and −0.8) (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>, <a class="elsevierStyleCrossRef" href="#sec0090">Supplementary Table 3</a>). Although patient numbers were low after Month 12, improvements in mean HAQ-DI scores appeared to be generally sustained through to Month 24 (−0.9 and −1.0, respectively).<elsevierMultimedia ident="fig0015"></elsevierMultimedia>SafetyIn total, 15 patients receiving tofacitinib treatment discontinued from the studies; 13 of these discontinuations were considered unrelated to study drug, and two patients (one each in the tofacitinib 5 and 10mg BID groups) discontinued due to AEs related to study drug (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). No serious AEs or deaths were reported in any treatment group. A higher proportion of patients reported treatment-emergent AEs (TEAEs) after Month 6 compared with the Month 0–3 and Month 3–6 treatment periods (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>During the first 3 months of treatment, the most frequently reported TEAEs were anemia for the placebo and tofacitinib 5mg BID groups, and anemia and urinary tract infection for the tofacitinib 10mg BID group; no TEAEs were reported in the methotrexate group (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>). One case each of hypotension and hematoma were with tofacitinib 5mg BID and one case of hypertensive crisis was reported with tofacitinib 10mg BID. Between Months 3 and 6, the most frequently reported TEAEs were hematuria, headache and increased blood creatine phosphokinase with tofacitinib 5mg BID, and anemia with tofacitinib 10mg BID. One case of non-melanoma skin cancer (NMSC; basal cell carcinoma) malignancy was reported in the tofacitinib 10mg BID group between Months 3 and 6. No TEAEs were reported in patients receiving methotrexate, and no particular TEAE was more frequent in the placebo group. Post-Month 6, the most frequently reported TEAEs for tofacitinib-treated patients were anemia, headache, influenza and increased blood creatine phosphokinase; no particular TEAE was more frequent in the methotrexate group (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>). Differences were observed between AEs reported for patients receiving tofacitinib 5 or 10mg BID post-6 months, with a higher number of reported headaches, influenza and gastrointestinal disorders (upper abdominal pain and dyspepsia) in patients receiving tofacitinib 10mg BID compared with those receiving tofacitinib 5mg BID. Post-Month 6, there was one other reported case of NMSC (basal cell carcinoma) malignancy in the tofacitinib 10mg BID group, and a single reported case of herpes zoster in the tofacitinib 5mg BID group; no other cases of herpes zoster were reported. One case each of tachycardia was reported with tofacitinib 5 and 10mg BID, respectively. There were no reported cases of TB, opportunistic infections, serious infections or gastrointestinal perforations.<elsevierMultimedia ident="tbl0015"></elsevierMultimedia>DiscussionThis post hoc analysis of the efficacy and safety of tofacitinib in Colombian patients with RA demonstrated that tofacitinib 5mg BID and tofacitinib 10mg BID reduced the signs and symptoms of RA, as measured by ACR20, ACR50 and ACR70 response rates and mean DAS28-4(ESR), and improved physical function, as measured by mean change from baseline in HAQ-DI. Although patient numbers were low post-Month 12, efficacy improvements were generally sustained through to Month 24 in the tofacitinib 5 and 10mg BID groups. Demographics were generally similar among the Colombian populations studied here and the global data, with the exception of race, where the majority of Colombian patients were non-white; however, additional analysis of this category was not conducted. Mean RA duration was generally slightly shorter (excluding placebo which was higher) and HAQ-DI was generally higher in the data reported here, compared with global data for these studies.<a class="elsevierStyleCrossRefs" href="#bib0415">29–34,38,39</a>Similar improvements in efficacy outcomes at Month 3 were observed for Colombian patients receiving tofacitinib 5mg BID and tofacitinib 10mg BID, compared with the Latin American population in tofacitinib phase III studies and generally similar efficacy outcomes compared with LTE studies.<a class="elsevierStyleCrossRef" href="#bib0460">38</a> The efficacy analyses presented here showed that ACR response rates, change from baseline in HAQ-DI, and mean DAS28-4(ESR) were also generally similar compared with the global phase III RA population.<a class="elsevierStyleCrossRefs" href="#bib0415">29–34,38</a>Unlike many bDMARDs, which require subcutaneous or intravenous administration, tofacitinib is administered orally. This may be particularly beneficial in Colombia, where some patients may not have easy access to resources related to transportation, storage and administration of these medications. However, patients receiving tofacitinib do require routine monitoring of neutrophils, lymphocytes, hemoglobin, liver enzymes and lipids, as well as baseline screening for TB and viral hepatitis. <a class="elsevierStyleCrossRef" href="#bib0485">43</a> Our results for Colombian patients with RA support the global findings that tofacitinib could provide an effective oral alternative to bDMARDs.There were no reported cases of serious AEs, serious infections, or deaths in any of the treatment groups, and the overall safety profile of tofacitinib was generally similar between the Colombian subpopulation and both the global phase III RA population<a class="elsevierStyleCrossRefs" href="#bib0415">29–34</a> and the Latin American population.<a class="elsevierStyleCrossRef" href="#bib0460">38</a> However, in interpreting these findings it is important to acknowledge that the global and Latin American populations included a larger number of patients, with greater total tofacitinib exposure analyzed, compared with the Colombian subpopulation. Two cases of NMSC malignancies were reported in the tofacitinib 10mg BID group. No cases of lymphoma, or lymphoproliferative disorders were reported in Colombian patients.No cases of TB were reported in this Colombian subpopulation, which is consistent with the low incidence reported in the Latin American and global phase III and LTE populations. <a class="elsevierStyleCrossRefs" href="#bib0415">29-34,38,39,44</a> It is important to note that patients enrolled into tofacitinib clinical trials were screened for latent or untreated TB before enrollment, and it is recommended that all patients (including those from countries where TB is not endemic) should be screened for TB before initiating tofacitinib treatment, as is already the case for patients using bDMARDs in other Latin American countries.<a class="elsevierStyleCrossRefs" href="#bib0475">41,42</a> Furthermore, previous reports have indicated that the risk of developing TB while receiving immunosuppressant therapy varies according to the background TB rate in the underlying population.<a class="elsevierStyleCrossRefs" href="#bib0490">44–47</a> The latest World Health Organization Global Tuberculosis Report listed incidence of TB in Colombia as intermediate, therefore monitoring for TB as a possible AE of special interest was important in this population.<a class="elsevierStyleCrossRef" href="#bib0355">17</a>Overall, fewer AEs, serious AEs and deaths were reported for the Colombian subpopulation compared with the Latin American and global populations; however, this is most likely the result of the small sample size in the Colombian subpopulation.<a class="elsevierStyleCrossRefs" href="#bib0415">29–34,38,39</a> Investigator-reported increases in blood creatine phosphokinase were observed in some patients receiving tofacitinib in this Colombian subpopulation; however, proportions of events were no higher than in the long-term extension studies in the Latin American population.<a class="elsevierStyleCrossRef" href="#bib0460">38</a> Similarly, throughout the entire global RA program generally, mean values for serum creatine phosphokinase remained within normal reference ranges.<a class="elsevierStyleCrossRef" href="#bib0510">48</a>Treatment with bDMARDs can increase the risk of infections and infestations compared with csDMARDs in patients in Latin American countries.<a class="elsevierStyleCrossRefs" href="#bib0515">49,50</a> No opportunistic infections or serious infections were reported in this analysis of Colombian patients, and there was one case of non-serious herpes zoster in the tofacitinib 5mg BID group; however, it should be noted that the comparatively low Colombian patient numbers may not enable generalization to the wider population. In the global tofacitinib studies, increased rates of herpes zoster were observed with tofacitinib treatment compared with placebo, but reports of complicated herpes zoster events have been rare for tofacitinib-treated patients in longer-term studies.<a class="elsevierStyleCrossRefs" href="#bib0415">29–35,51</a> Therefore, there were no cases of TB, opportunistic infection, gastrointestinal perforation, or serious cardiovascular AEs, and few cases of herpes zoster or malignancies were reported in Colombian patients receiving tofacitinib in these phase III studies. However, it remains important to routinely monitor patients for these AEs, as is already recommended in Colombian guidelines for other immunosuppressant therapies.<a class="elsevierStyleCrossRefs" href="#bib0340">14,16</a>With the exception of ORAL Start, in which patients were MTX-naïve, the patient populations among ORAL Scan, ORAL Solo and ORAL Sync were generally very similar and were DMARD-IR. Therefore, this post hoc analysis was somewhat limited by the use of pooled data, which can provide a heterogeneous patient population. Moreover, there were some differences in designs and methodologies of the phase III studies included in this analysis. As such, efficacy analyses included patients from ORAL Scan, ORAL Solo and ORAL Sync only, as patients in ORAL Start were methotrexate-naïve, and represented a different patient population that was not directly comparable. A greater proportion of Colombian patients were identified as non-white compared with the global populations; however, further investigation of race within the non-white listing category was not conducted. At all time points, patient numbers in the placebo and methotrexate groups were too low to allow meaningful comparison to be made with the tofacitinib groups, and therefore the exclusion of these groups from efficacy analyses limits the interpretation of the findings. For completeness, placebo and methotrexate groups were included in the safety analysis; however, the placebo group was smaller and had shorter exposure than the tofacitinib groups, which limits meaningful between group comparisons. Another important limitation of this post hoc analysis is the low patient numbers for all groups post-Month 12. Due to these low patient numbers, efficacy outcomes for tofacitinib groups post-Month 12, and any safety differences between active treatment and placebo post-Month 12, should be interpreted with caution. Due to the small sample sizes of this analysis of the Colombian sub-population, no formal statistical analyses were conducted. Also analyses were not powered to identify differences in efficacy or safety between treatment groups, therefore, conclusions are not definitive and are based on descriptive analyses only.ConclusionTwo studies observed that from one-third to half of patients with RA in Colombia may be achieving remission;<a class="elsevierStyleCrossRefs" href="#bib0335">13,15</a> as such, there may be an unmet clinical need in Colombia for new RA therapies that can improve treatment outcomes for patients who have an inadequate response to csDMARDs and bDMARDs. Our results suggest that tofacitinib 5mg BID and tofacitinib 10mg BID were efficacious over 12 months (Month 24 data also presented) for the treatment of RA in Colombian patients in phase III studies; this was consistent with the findings from the global phase III and Latin American populations.The data presented here for the Colombian sub-population suggest that there are no major differences in terms of efficacy or safety compared with patients from Latin American or global populations. Therefore, no significant differential factor emerged between the Colombian populations and other populations, which may be important when considering that incidences of some infections and neglected tropical diseases are more frequent in Latin American countries.<a class="elsevierStyleCrossRefs" href="#bib0530">52,53</a>Both tofacitinib doses demonstrated a manageable safety profile in the Colombian subpopulation. Overall, our results support the favorable benefit-risk of tofacitinib as an oral alternative to bDMARDs for the treatment of patients with RA in Colombia.FundingThis study was funded by Pfizer Inc.Author roles and contributionsAll authors meet the criteria for authorship and have approved the final article.Conflict of interestP Vélez and W Otero Escalante have no conflicts of interest to declare. JJ Jaller has no conflicts of interest to declare. EG García and K Persand were employees and shareholders of Pfizer Inc at the time the studies were conducted. R Rojo, D Chapman, and G Matiz are employees of Pfizer Inc." "textoCompletoSecciones" => array:1 [ "secciones" => array:14 [ 0 => array:3 [ "identificador" => "xres1190600" "titulo" => "Abstract" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objective" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1109938" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1190601" "titulo" => "Resumen" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0030" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Objetivo" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Métodos" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Resultados" ] 4 => array:2 [ "identificador" => "abst0050" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1109939" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Methods" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Patients" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Study designs" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Efficacy endpoints" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Safety endpoints" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Statistical analysis" ] ] ] 6 => array:3 [ "identificador" => "sec0040" "titulo" => "Results" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0045" "titulo" => "Patients" ] 1 => array:2 [ "identificador" => "sec0050" "titulo" => "Efficacy" ] 2 => array:2 [ "identificador" => "sec0055" "titulo" => "Safety" ] ] ] 7 => array:2 [ "identificador" => "sec0060" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0065" "titulo" => "Conclusion" ] 9 => array:2 [ "identificador" => "sec0070" "titulo" => "Funding" ] 10 => array:2 [ "identificador" => "sec0075" "titulo" => "Author roles and contributions" ] 11 => array:2 [ "identificador" => "sec0080" "titulo" => "Conflict of interest" ] 12 => array:2 [ "identificador" => "xack406795" "titulo" => "Acknowledgments" ] 13 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2017-12-22" "fechaAceptado" => "2018-08-27" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1109938" "palabras" => array:6 [ 0 => "Colombia" 1 => "Efficacy" 2 => "Janus kinase" 3 => "Rheumatoid arthritis" 4 => "Safety" 5 => "Tofacitinib" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1109939" "palabras" => array:6 [ 0 => "Colombia" 1 => "Eficacia" 2 => "Janus kinasa" 3 => "Artritis reumatoide" 4 => "Seguridad" 5 => "Tofacitinib" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "IntroductionTofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). ObjectiveTo conduct a post hoc analysis of tofacitinib efficacy and safety in Colombian patients enrolled in global phase III studies. MethodsData were pooled from Colombian patients with RA across four phase III tofacitinib studies: ORAL Sync, ORAL Scan, ORAL Solo, and ORAL Start. Patients received tofacitinib 5 or 10mg twice daily, methotrexate (ORAL Start only), or placebo as single therapy (ORAL Start and ORAL Solo), or in combination with csDMARDs (ORAL Sync and ORAL Scan). Data were pooled from three studies with similar patient populations (Sync, Scan, Solo) for efficacy analyses, and from all studies for safety analyses, up to Month 24. The efficacy analysis excluded ORAL Start due to the methotrexate-naive patient population, and placebo and methotrexate groups, due to low patient numbers. ResultsData pooled included 77 patients for efficacy, and 125 for safety analyses. Tofacitinib-treated patients showed improved American College of Rheumatology 20/50/70 response rates, a mean Disease Activity Score 28-4 (erythrocyte sedimentation rate), and a mean change from baseline in Health Assessment Questionnaire-Disability Index. Improvements were sustained in Months 12–24, although patient numbers were low post-Month 12. The most frequently reported adverse events were anemia, headache, influenza, and increased blood creatine phosphokinase. No tuberculosis cases, serious adverse events, or deaths were reported, and few cases of herpes zoster or malignancies occurred. ConclusionsTofacitinib reduced RA signs and symptoms, and improved physical function. The efficacy and safety of tofacitinib in this Colombian sub-population were consistent with data from global phase III studies." "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objective" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "IntroducciónTofacitinib es un inhibidor oral de la janus kinasa para el tratamiento de la artritis reumatoide (AR). ObjetivoAnálisis post hoc para evaluar la eficacia y seguridad de tofacitinib en los pacientes colombianos que participaron en los estudios globales de fase III. MétodosLa información se obtuvo de los pacientes colombianos con AR que participaron en 4 de los estudios de tofacitinib de fase III: ORAL Sync, ORAL Scan, ORAL Solo y ORAL Start. Los pacientes recibieron tofacitinib 5 o 10mg 2 veces al día, ya sea en monoterapia (ORAL Start y ORAL Solo) o en combinación con csDMARDs (ORAL Scan y ORAL Sync), metotrexate (ORAL Start) o placebo. Para el análisis de eficacia se utilizaron 3 estudios que incluyeron poblaciones similares (Sync, Scan y Solo) y para el análisis de seguridad se utilizaron todos los estudios, hasta el mes 24. El análisis de eficacia excluyó tanto el estudio ORAL Start debido a población metotrexate naive como a los grupos placebo o metotrexate debido al bajo número de pacientes. ResultadosSe incluyeron 77 pacientes para el análisis de eficacia y 125 para seguridad. Los pacientes tratados con tofacitinib mostraron mejorías en las tasas de respuestas del American College of Rheumatology (ACR) 20/50/70, en el promedio del Disease Activity Score (DAS) 28-4 (velocidad de sedimentación globular) y en el cambio promedio desde la basal en el Health Assessment Questionnaire-Disability Index (HAQ-DI). Las mejorías fueron sostenidas desde el mes 12 al mes 24, aunque el número de pacientes luego del mes 12 fue bajo. Los eventos adversos más frecuentemente reportados fueron anemia, cefalea, influenza e incremento de la creatin-fosfoquinasa sérica. No se reportaron casos de tuberculosis, eventos adversos serios o muertes. Ocurrieron casos poco frecuentes de herpes zoster y malignidades. ConclusionesTofacitinib redujo los signos y síntomas de la AR y mejoró la función física. La eficacia y seguridad en esta subpoblación colombiana fue consistente con los resultados de los pacientes que participaron en los estudios globales de fase III." "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0030" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Objetivo" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Métodos" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Resultados" ] 4 => array:2 [ "identificador" => "abst0050" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:3 [ "etiqueta" => "1" "nota" => "Indicated affiliation at the time, the work was conducted." "identificador" => "fn0005" ] ] "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:1 [ 0 => array:4 [ "apendice" => "<elsevierMultimedia ident="upi0005"></elsevierMultimedia>" "etiqueta" => "Appendix A" "titulo" => "Supplementary data" "identificador" => "sec0090" ] ] ] ] "multimedia" => array:7 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 3855 "Ancho" => 2470 "Tamanyo" => 332115 ] ] "descripcion" => array:1 [ "en" => "Proportion of responders for (A) ACR20, (B) ACR50 and (C) ACR70 (SE) over time for the tofacitinib 5 and 10mg BID groups in the efficacy subpopulation (FAS, observed). ACR20/50/70: American College of Rheumatology 20/50/70 response rates; BID: twice daily; FAS: full analysis set; SE, standard error. N represents the numbers of patients with non-missing ACR response. Efficacy analyses were based on three studies: ORAL Scan, ORAL Solo and ORAL Sync." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1365 "Ancho" => 2493 "Tamanyo" => 121279 ] ] "descripcion" => array:1 [ "en" => "Mean (SE) DAS28-4(ESR) over time for the tofacitinib 5 and 10mg BID groups in the efficacy subpopulation (FAS, observed). BID: twice daily; DAS28-4(ESR): Disease Activity Score-erythrocyte sedimentation rate; FAS: full analysis set; SE: standard error. N represents the numbers of patients with non-missing DAS28-4(ESR). Efficacy analyses were based on three studies: ORAL Scan, ORAL Solo and ORAL Sync." ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1371 "Ancho" => 2496 "Tamanyo" => 134477 ] ] "descripcion" => array:1 [ "en" => "Mean (SE) change from baseline in HAQ-DI (SE) over time for the tofacitinib 5 and 10mg BID groups in the efficacy subpopulation (FAS, observed). BID: twice daily; FAS: full analysis set; HAQ-DI: Health Assessment Questionnaire-Disability Index; SE: standard error. N represents the numbers of patients with non-missing HAQ-DI. Efficacy analyses were based on three studies: ORAL Scan, ORAL Solo and ORAL Sync." ] ] 3 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "BID: twice daily; BMI: body mass index; DAS28-4(ESR): Disease Activity Score28-4(erythrocyte sedimentation rate); HAQ-DI: Health Assessment Questionnaire-Disability Index; Other: Black/Asian/Hispanic; MTX: methotrexate; RA: rheumatoid arthritis; SD: standard deviation." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Efficacy analyses population<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a></th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="4" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Safety analyses population<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a></th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Tofacitinib5mg BID(n=33) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Tofacitinib10mg BID(n=32) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Tofacitinib5mg BID(n=53) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Tofacitinib10mg BID(n=51) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Placebo(n=12) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">MTX(n=9) \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mean age, years (range) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">51.5 (31–74) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">51.6 (29–74) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">51.0 (26–74) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">50.9 (21–74) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">52.4 (32–74) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">45.8 (20–67) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Female, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">28 (84.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">30 (93.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">45 (84.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">46 (90.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 (91.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 (88.9) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Race, n (%)</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">White \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (3.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (2.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Other \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">33 (100.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">31 (96.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">53 (100.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">50 (98.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 (100.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (100.0) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mean RA duration, years (range) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.5 (0.2–25.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10.1 (0.9–35.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.5 (0.1–25.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.2 (0.1–35.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13.0 (0.9–40.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.6 (0.1–14.0) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mean BMI, kg/m2(range) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">26.6 (18.0–37.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25.6 (14.4–37.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25.8 (18–37.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25.7 (14.4–37.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24.5 (14.6–37.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">23.2 (16.9–32.5) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Baseline DAS28-4(ESR), mean (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6.3 (0.79) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6.2 (1.09) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6.5 (1.00) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6.4 (1.16) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6.7 (0.71) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.1 (0.96) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Baseline HAQ-DI, mean (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.6 (0.76) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.8 (0.66) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.7 (0.78) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.7 (0.63) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.6 (0.73) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.9 (0.64) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Previous RA treatment, n (%)</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Methotrexate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">32 (97.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">32 (100.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">32 (60.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">32 (62.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 (91.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Anti-malarial \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (9.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 (12.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 (13.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (17.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (22.2) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Leflunomide \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (6.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (3.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (16.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sulfasalazine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (6.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (3.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (8.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2031598.png" ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "Efficacy analyses were based on three studies: ORAL Scan, ORAL Solo and ORAL Sync." ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "b" "nota" => "Safety analyses were based on four studies: ORAL Scan, ORAL Solo, ORAL Sync and ORAL Start." ] ] ] "descripcion" => array:1 [ "en" => "Patient demographics and baseline characteristics by treatment sequence for patients included in the efficacy and safety analyses." ] ] 4 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "AE: adverse event; BID: twice daily; MTX: methotrexate; NA: not applicable; SAE, serious adverse event; TEAE: treatment-emergent adverse event." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Tofacitinib 5mg BID \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Tofacitinib 10mg BID \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Placebo \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">MTX \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">n (%) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">(n=53) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">(n=51) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">(n=12) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">(n=9) \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Discontinuations</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Related to study drug</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">AE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (1.9)<a class="elsevierStyleCrossRef" href="#tblfn0015">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (2.0)<a class="elsevierStyleCrossRef" href="#tblfn0020">b</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Lack of efficacy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (11.1) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Not related to study drug \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 (7.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (17.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (16.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (22.2) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">AEs</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TEAE Month 0–3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">21 (39.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18 (35.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 (58.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TEAE Month 3–6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">19 (34.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">21 (36.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (25.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TEAE Month 6+ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">34 (77.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">34 (77.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 (66.7) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SAEs \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Deaths \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2031597.png" ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0015" "etiqueta" => "a" "nota" => "Patient discontinued due to increased blood creatine phosphokinase, but not adjudicated SAE" ] 1 => array:3 [ "identificador" => "tblfn0020" "etiqueta" => "b" "nota" => "Patient discontinued due a persistent elevation in function liver tests (alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase), but not adjudicated SAE Placebo patients advanced to tofacitinib 5 or 10mg BID at Month 3 or 6, depending on American College of Rheumatology 20 response rate. Safety analyses were based on data from four studies: ORAL Scan, ORAL Solo, ORAL Sync and ORAL Start." ] ] ] "descripcion" => array:1 [ "en" => "Summary of safety outcomes for all treatment groups." ] ] 5 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "BID: twice daily; MTX: methotrexate; NA: not applicable; TEAE: treatment-emergent adverse event.Placebo patients could advance to tofacitinib 5 or 10mg BID at Month 3 depending on American College of Rheumatology 20 response rate; all remaining placebo patients advanced at Month 6 to tofacitinib 5 or 10mg BID. Abdominal pain upper was not listed for Month 0–3.Safety analyses were based on data from four studies: ORAL Scan, ORAL Solo, ORAL Sync and ORAL Start." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="4" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Months 0–3</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="4" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Months 3–6</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="3" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Month 6+</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Tofacitinib 5mg BID \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Tofacitinib 10mg BID \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Placebo \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">MTX \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Tofacitinib 5mg BID \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Tofacitinib 10mg BID \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Placebo \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">MTX \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Tofacitinib 5mg BID \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Tofacitinib 10mg BID \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">MTX \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">n (%) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">(n=53) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">(n=51) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">(n=12) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">(n=9) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">(n=55) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">(n=57) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">(n=4) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">(n=9) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">(n=44) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">(n=44) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">(n=9) \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Anemia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (9.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (5.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (25) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (3.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (8.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 (13.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (11.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (11.1) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Diarrhea \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (8.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 (9.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 (9.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Abdominal pain (upper) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (1.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (25.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (6.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (11.1) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Dyspepsia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (3.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (1.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (6.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Bronchitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (1.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (2.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (1.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (2.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (6.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Urinary tract infection \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (5.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (5.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (4.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (11.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (11.1) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Influenza \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (1.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (1.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (11.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 (15.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (11.1) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Blood creatine phosphokinase increased \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (5.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (3.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (5.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (3.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 (13.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (6.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hypercholesterolemia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (2.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (1.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (2.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (6.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hypertriglyceridemia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (1.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (2.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (1.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 (9.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 (9.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Headache \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (1.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (2.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (8.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (5.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (3.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (25.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 (9.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 (15.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hematuria \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (3.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (5.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 (9.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (2.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Onychomycosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (8.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (2.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (2.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Erythema \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (8.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Skin lesion \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (8.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (2.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2031599.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Most frequently reported TEAEs (≥5%) in any treatment group." ] ] 6 => array:5 [ "identificador" => "upi0005" "tipo" => "MULTIMEDIAECOMPONENTE" "mostrarFloat" => false "mostrarDisplay" => true "Ecomponente" => array:2 [ "fichero" => "mmc1.docx" "ficheroTamanyo" => 49180 ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:54 [ 0 => array:3 [ "identificador" => "bib0275" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Current therapies in rheumatoid arthritis: a Latin American perspective" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "R. Burgos-Vargas" 1 => "L.J. Catoggio" 2 => "C. Galarza-Maldonado" 3 => "K. Ostojich" 4 => "M.H. Cardiel" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.reuma.2012.09.001" "Revista" => array:6 [ "tituloSerie" => "Reumatol Clin" "fecha" => "2013" "volumen" => "9" "paginaInicial" => "106" "paginaFinal" => "112" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23337169" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0280" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The epidemiology of rheumatoid arthritis in a cohort of Colombian patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "J.E. Machado-Alba" 1 => "A.F. Ruiz" 2 => "D.A. Medina Morales" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Rev Colomb Reumatol" "fecha" => "2015" "volumen" => "22" "paginaInicial" => "148" "paginaFinal" => "152" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0285" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Rheumatoid arthritis in African Colombians from Quibdo" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "J.M. Anaya" 1 => "P.A. Correa" 2 => "R.D. Mantilla" 3 => "F. Jimenez" 4 => "T. Kuffner" 5 => "J.M. McNicholl" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Semin Arthritis Rheum" "fecha" => "2001" "volumen" => "31" "paginaInicial" => "191" "paginaFinal" => "198" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11740799" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0290" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prevalencia de artritis reumatoide en Colombia: una aproximación basada en la carga de la enfermedad durante el año 2005" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "J.A. Díaz-Rojas" 1 => "F.A. Dávila-Ramírez" 2 => "G. Quintana-López" 3 => "F. Aristizábal-Gutiérrez" 4 => "P. Brown" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Rev Colomb Reumatol" "fecha" => "2016" "volumen" => "23" "paginaInicial" => "11" "paginaFinal" => "16" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0295" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.S. Smolen" 1 => "R. Landewé" 2 => "J. Bijlsma" 3 => "G. Burmester" 4 => "K. Chatzidionysiou" 5 => "M. Dougados" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/annrheumdis-2016-210715" "Revista" => array:6 [ "tituloSerie" => "Ann Rheum Dis" "fecha" => "2017" "volumen" => "76" "paginaInicial" => "960" "paginaFinal" => "977" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28264816" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0300" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.A. Singh" 1 => "K.G. Saag" 2 => "S.L. Bridges Jr." 3 => "E.A. Akl" 4 => "R.R. Bannuru" 5 => "M.C. Sullivan" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/art.39977" "Revista" => array:6 [ "tituloSerie" => "Arthritis Rheumatol" "fecha" => "2016" "volumen" => "68" "paginaInicial" => "1" "paginaFinal" => "26" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27870508" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0305" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "First Latin American position paper on the pharmacological treatment of rheumatoid arthritis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "M.H. Cardiel" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Rheumatology (Oxford)" "fecha" => "2006" "volumen" => "45" "numero" => "Suppl 2" "paginaInicial" => "ii7" "paginaFinal" => "ii22" ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0310" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Treating rheumatoid arthritis in Latin America: current challenges and future treatment strategies" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "M.H. Cardiel" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Int J Clin Rheumatol" "fecha" => "2012" "volumen" => "7" "paginaInicial" => "139" "paginaFinal" => "142" ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0315" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Treatment of early rheumatoid arthritis in a multinational inception cohort of Latin American patients: the GLADAR experience" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.H. Cardiel" 1 => "B.A. Pons-Estel" 2 => "M.P. Sacnun" 3 => "D. Wojdyla" 4 => "V. Saurit" 5 => "J.C. Marcos" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/RHU.0b013e31826d6610" "Revista" => array:6 [ "tituloSerie" => "J Clin Rheumatol" "fecha" => "2012" "volumen" => "18" "paginaInicial" => "327" "paginaFinal" => "335" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23047532" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0320" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Challenges in the management of rheumatoid arthritis in developing countries" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "G.M. Mody" 1 => "M.H. Cardiel" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.berh.2008.04.003" "Revista" => array:6 [ "tituloSerie" => "Best Pract Res Clin Rheumatol" "fecha" => "2008" "volumen" => "22" "paginaInicial" => "621" "paginaFinal" => "641" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18783741" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0325" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Long-term impact of early treatment on radiographic progression in rheumatoid arthritis: a meta-analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "A. Finckh" 1 => "M.H. Liang" 2 => "C.M. van Herckenrode" 3 => "P.P. de" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/art.22353" "Revista" => array:6 [ "tituloSerie" => "Arthritis Rheum" "fecha" => "2006" "volumen" => "55" "paginaInicial" => "864" "paginaFinal" => "872" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17139662" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0330" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tratamiento de la artritis reumatoide en Colombia. Applicación práctica de los conceptos teóricos por parte de los reumatólogos colombianos" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "C.V. Caballero Uribe" 1 => "J.D. Londoño" 2 => "J.P. Chalem" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Rev Colomb Reumatol" "fecha" => "2002" "volumen" => "9" "paginaInicial" => "242" "paginaFinal" => "250" ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0335" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Epidemiological profile of Colombian patients with rheumatoid arthritis in a specialized care clinic" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "W. Bautista-Molano" 1 => "D. Fernandez-Avila" 2 => "R. Jimenez" 3 => "R. Cardozo" 4 => "A. Marin" 5 => "M.D. Soler" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.reuma.2015.11.009" "Revista" => array:6 [ "tituloSerie" => "Reumatol Clin" "fecha" => "2016" "volumen" => "12" "paginaInicial" => "313" "paginaFinal" => "318" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26708736" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0340" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Recomendaciones del comité de expertos de la Asociación Colombiana de Rheumatología para el empleo de terapia bloqueadora del factor de necrosis tumoral en artritis reumatoide" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.D. Londoño" 1 => "J.R. Gutiérrez" 2 => "M.D. Cortés" 3 => "O.U. Uribe" 4 => "H. González Buritica" 5 => "C.V. Caballero Uribe" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Rev Colomb Reumatol" "fecha" => "2001" "volumen" => "8" "paginaInicial" => "296" "paginaFinal" => "302" ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0345" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effectiveness of treatment with biologic- and disease-modifying antirheumatic drugs in rheumatoid arthritis patients in Colombia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "J.E. Machado-Alba" 1 => "A.F. Ruiz" 2 => "M.E. Machado-Duque" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/ijcp.12809" "Revista" => array:6 [ "tituloSerie" => "Int J Clin Pract" "fecha" => "2016" "volumen" => "70" "paginaInicial" => "506" "paginaFinal" => "511" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27238964" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0350" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Guía de Práctica Clínica artritis reumatoide" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "Universidad Nacional de Colombia" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:1 [ "fecha" => "2014" ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0355" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Global Tuberculosis Report" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "World Health Organization" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:1 [ "fecha" => "2016" ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0360" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Efficacy and safety of 40 mg adalimumab twice per month in Colombian patients with rheumatoid arthritis (RA) with failure of conventional treatment. An open study in a group of unselected patients “Real life study”" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Londono" 1 => "J. Molina" 2 => "R. Guzman" 3 => "C. Caballero" 4 => "M. Chalem" 5 => "M. Janiot" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Ann Rheum Dis" "fecha" => "2005" "volumen" => "64" "numero" => "Suppl. III" "paginaInicial" => "475" ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0365" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cambio en la capacidad funcional, calidad de vida y actividad de la enfermedad, en un grupo de pacientes colombianos con artritis reumatoide refractaria al tratamiento convencional, que recibieron terapia con Infliximab como medicamento de rescate" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P.J. Londoño" 1 => "A. Fernandez" 2 => "G. Daniel" 3 => "J.C. Salazar" 4 => "D.L. Saiibi" 5 => "J.F. Molina" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Rev Med" "fecha" => "2009" "volumen" => "17" "paginaInicial" => "40" "paginaFinal" => "49" ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0370" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical disease activity and acute phase reactant levels are discordant among patients with active rheumatoid arthritis: acute phase reactant levels contribute separately to predicting outcome at one year" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Kay" 1 => "O. Morgacheva" 2 => "S.P. Messing" 3 => "J.M. Kremer" 4 => "J.D. Greenberg" 5 => "G.W. Reed" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/ar4469" "Revista" => array:5 [ "tituloSerie" => "Arthritis Res Ther" "fecha" => "2014" "volumen" => "16" "paginaInicial" => "R40" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24485007" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0375" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Measures of rheumatoid arthritis disease activity: patient (PtGA) and Provider (PrGA) Global Assessment of Disease Activity, Disease Activity Score (DAS) and Disease Activity Score with 28-Joint Counts (DAS28), Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), Patient Activity Score (PAS) and Patient Activity Score-II (PASII), Routine Assessment of Patient Index Data (RAPID), Rheumatoid Arthritis Disease Activity Index (RADAI) and Rheumatoid Arthritis Disease Activity Index-5 (RADAI-5), Chronic Arthritis Systemic Index (CASI), Patient-Based Disease Activity Score With ESR (PDAS1) and Patient-Based Disease Activity Score without ESR (PDAS2), and Mean Overall Index for Rheumatoid Arthritis (MOI-RA)" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "J.K. Anderson" 1 => "L. Zimmerman" 2 => "L. Caplan" 3 => "K. Michaud" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Arthritis Care Res (Hoboken)" "fecha" => "2011" "volumen" => "63" "numero" => "Suppl 11" "paginaInicial" => "S14" "paginaFinal" => "S36" ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0380" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Correlation between rapid-3, DAS28, CDAI and SDAI as a measure of disease activity in a cohort of Colombian patients with rheumatoid arthritis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.G.B. Munoz" 1 => "R.B. Giraldo" 2 => "A.M. Santos" 3 => "J.M. Bello-Gualteros" 4 => "J.C. Rueda" 5 => "E.L. Saldarriaga" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10067-016-3521-5" "Revista" => array:6 [ "tituloSerie" => "Clin Rheumatol" "fecha" => "2017" "volumen" => "36" "paginaInicial" => "1143" "paginaFinal" => "1148" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28013433" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0385" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Phase IIb dose-ranging study of the oral JAK inhibitor tofacitinib (CP-690,550) or adalimumab monotherapy versus placebo in patients with active rheumatoid arthritis with an inadequate response to disease-modifying antirheumatic drugs" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R. Fleischmann" 1 => "M. Cutolo" 2 => "M.C. Genovese" 3 => "E.B. Lee" 4 => "K.S. Kanik" 5 => "S. Sadis" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/art.33383" "Revista" => array:6 [ "tituloSerie" => "Arthritis Rheum" "fecha" => "2012" "volumen" => "64" "paginaInicial" => "617" "paginaFinal" => "629" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21952978" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0390" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A phase IIb dose-ranging study of the oral JAK inhibitor tofacitinib (CP-690,550) versus placebo in combination with background methotrexate in patients with active rheumatoid arthritis and an inadequate response to methotrexate alone" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.M. Kremer" 1 => "S. Cohen" 2 => "B.E. Wilkinson" 3 => "C.A. Connell" 4 => "J.L. French" 5 => "J. Gomez-Reino" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/art.33419" "Revista" => array:6 [ "tituloSerie" => "Arthritis Rheum" "fecha" => "2012" "volumen" => "64" "paginaInicial" => "970" "paginaFinal" => "981" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22006202" "web" => "Medline" ] ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0395" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The safety and efficacy of a JAK inhibitor in patients with active rheumatoid arthritis: results of a double-blind, placebo-controlled phase IIa trial of three dosage levels of CP-690,550 versus placebo" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.M. Kremer" 1 => "B.J. Bloom" 2 => "F.C. Breedveld" 3 => "J.H. Coombs" 4 => "M.P. Fletcher" 5 => "D. Gruben" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/art.24567" "Revista" => array:6 [ "tituloSerie" => "Arthritis Rheum" "fecha" => "2009" "volumen" => "60" "paginaInicial" => "1895" "paginaFinal" => "1905" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19565475" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0400" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Open-label tofacitinib and double-blind atorvastatin in rheumatoid arthritis patients: a randomised study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "I.B. McInnes" 1 => "H.Y. Kim" 2 => "S.H. Lee" 3 => "D. Mandel" 4 => "Y.W. Song" 5 => "C.A. Connell" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/annrheumdis-2012-202442" "Revista" => array:6 [ "tituloSerie" => "Ann Rheum Dis" "fecha" => "2014" "volumen" => "73" "paginaInicial" => "124" "paginaFinal" => "131" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23482473" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0405" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Phase II study of tofacitinib (CP-690,550) combined with methotrexate in patients with rheumatoid arthritis and an inadequate response to methotrexate" "autores" => array:1 [ 0 => array:3 [ "colaboracion" => "Tofacitinib Study Investigators" "etal" => false "autores" => array:5 [ 0 => "Y. Tanaka" 1 => "M. Suzuki" 2 => "H. Nakamura" 3 => "S. Toyoizumi" 4 => "S.H. Zwillich" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Arthritis Care Res (Hoboken)" "fecha" => "2011" "volumen" => "63" "paginaInicial" => "1150" "paginaFinal" => "1158" ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0410" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Efficacy and safety of tofacitinib as monotherapy in Japanese patients with active rheumatoid arthritis: a 12-week, randomized, phase 2 study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "Y. Tanaka" 1 => "T. Takeuchi" 2 => "H. Yamanaka" 3 => "H. Nakamura" 4 => "S. Toyoizumi" 5 => "S. Zwillich" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3109/14397595.2014.995875" "Revista" => array:6 [ "tituloSerie" => "Mod Rheumatol" "fecha" => "2015" "volumen" => "25" "paginaInicial" => "514" "paginaFinal" => "521" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25496464" "web" => "Medline" ] ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0415" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Placebo-controlled trial of tofacitinib monotherapy in rheumatoid arthritis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R. Fleischmann" 1 => "J. Kremer" 2 => "J. Cush" 3 => "H. Schulze-Koops" 4 => "C.A. Connell" 5 => "J.D. Bradley" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1109071" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2012" "volumen" => "367" "paginaInicial" => "495" "paginaFinal" => "507" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22873530" "web" => "Medline" ] ] ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0420" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tofacitinib in combination with nonbiologic disease-modifying antirheumatic drugs in patients with active rheumatoid arthritis: a randomized trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Kremer" 1 => "Z.-G. Li" 2 => "S. Hall" 3 => "R. Fleischmann" 4 => "M. Genovese" 5 => "E. Martin-Mola" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.7326/0003-4819-159-4-201308200-00006" "Revista" => array:6 [ "tituloSerie" => "Ann Intern Med" "fecha" => "2013" "volumen" => "159" "paginaInicial" => "253" "paginaFinal" => "261" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24026258" "web" => "Medline" ] ] ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib0425" "etiqueta" => "31" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tofacitinib (CP-690,550) in patients with rheumatoid arthritis receiving methotrexate: twelve-month data from a twenty-four-month phase III randomized radiographic study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D. van der Heijde" 1 => "Y. Tanaka" 2 => "R. Fleischmann" 3 => "E. Keystone" 4 => "J. Kremer" 5 => "C. Zerbini" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/art.37816" "Revista" => array:6 [ "tituloSerie" => "Arthritis Rheum" "fecha" => "2013" "volumen" => "65" "paginaInicial" => "559" "paginaFinal" => "570" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23348607" "web" => "Medline" ] ] ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib0430" "etiqueta" => "32" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tofacitinib or adalimumab versus placebo in rheumatoid arthritis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R.F. van Vollenhoven" 1 => "R. Fleischmann" 2 => "S. Cohen" 3 => "E.B. Lee" 4 => "J.A. García Meijide" 5 => "S. Wagner" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1112072" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2012" "volumen" => "367" "paginaInicial" => "508" "paginaFinal" => "519" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22873531" "web" => "Medline" ] ] ] ] ] ] ] ] 32 => array:3 [ "identificador" => "bib0435" "etiqueta" => "33" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tofacitinib versus methotrexate in rheumatoid arthritis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "E.B. Lee" 1 => "R. Fleischmann" 2 => "S. Hall" 3 => "B. Wilkinson" 4 => "J. Bradley" 5 => "D. Gruben" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1310476" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2014" "volumen" => "370" "paginaInicial" => "2377" "paginaFinal" => "2386" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24941177" "web" => "Medline" ] ] ] ] ] ] ] ] 33 => array:3 [ "identificador" => "bib0440" "etiqueta" => "34" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tofacitinib (CP-690,550) in combination with methotrexate in patients with active rheumatoid arthritis with an inadequate response to tumour necrosis factor inhibitors: a randomised phase 3 trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "G.R. Burmester" 1 => "R. Blanco" 2 => "C. Charles-Schoeman" 3 => "J. Wollenhaupt" 4 => "C. Zerbini" 5 => "B. Benda" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(12)61424-X" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2013" "volumen" => "381" "paginaInicial" => "451" "paginaFinal" => "460" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23294500" "web" => "Medline" ] ] ] ] ] ] ] ] 34 => array:3 [ "identificador" => "bib0445" "etiqueta" => "35" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Safety and efficacy of tofacitinib, an oral Janus kinase inhibitor, for the treatment of rheumatoid arthritis in open-label, longterm extension studies" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Wollenhaupt" 1 => "J. Silverfield" 2 => "E.B. Lee" 3 => "J.R. Curtis" 4 => "S.P. Wood" 5 => "K. Soma" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3899/jrheum.130683" "Revista" => array:6 [ "tituloSerie" => "J Rheumatol" "fecha" => "2014" "volumen" => "41" "paginaInicial" => "837" "paginaFinal" => "852" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24692527" "web" => "Medline" ] ] ] ] ] ] ] ] 35 => array:3 [ "identificador" => "bib0450" "etiqueta" => "36" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tofacitinib, an oral Janus kinase inhibitor, as monotherapy or with background methotrexate, in Japanese patients with rheumatoid arthritis: an open-label, long-term extension study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "H. Yamanaka" 1 => "Y. Tanaka" 2 => "T. Takeuchi" 3 => "N. Sugiyama" 4 => "H. Yuasa" 5 => "S. Toyoizumi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/s13075-016-0932-2" "Revista" => array:5 [ "tituloSerie" => "Arthritis Res Ther" "fecha" => "2016" "volumen" => "18" "paginaInicial" => "34" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26818974" "web" => "Medline" ] ] ] ] ] ] ] ] 36 => array:3 [ "identificador" => "bib0455" "etiqueta" => "37" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tofacitinib, an oral Janus kinase inhibitor, in the treatment of rheumatoid arthritis: safety and efficacy in open-label, long-term extension studies over 9 years" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Wollenhaupt" 1 => "J. Silverfield" 2 => "E.B. Lee" 3 => "K. Terry" 4 => "K. Kwok" 5 => "S. Strengholt" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/art.39972" "Revista" => array:6 [ "tituloSerie" => "Arthritis Rheumatol" "fecha" => "2017" "volumen" => "69" "paginaInicial" => "683" "paginaFinal" => "684" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27788282" "web" => "Medline" ] ] ] ] ] ] ] ] 37 => array:3 [ "identificador" => "bib0460" "etiqueta" => "38" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tofacitinib, an oral Janus kinase inhibitor, for the treatment of Latin American patients with rheumatoid arthritis: pooled efficacy and safety analyses of Phase 3 and long-term extension studies" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S.C. Radominski" 1 => "M.H. Cardiel" 2 => "G. Citera" 3 => "A. Goecke" 4 => "J.J. Jaller" 5 => "A.B. Lomonte" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:2 [ "tituloSerie" => "Reumatol Clin" "fecha" => "2016" ] ] ] ] ] ] 38 => array:3 [ "identificador" => "bib0465" "etiqueta" => "39" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Safety of tofacitinib in the treatment of rheumatoid arthritis in Latin America compared with the rest of the world population" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "O.M. Castañeda" 1 => "F.J. Romero" 2 => "A. Salinas" 3 => "G. Citera" 4 => "E. Mysler" 5 => "O. Rillo" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/RHU.0000000000000498" "Revista" => array:6 [ "tituloSerie" => "J Clin Rheumatol" "fecha" => "2017" "volumen" => "23" "paginaInicial" => "193" "paginaFinal" => "199" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28145906" "web" => "Medline" ] ] ] ] ] ] ] ] 39 => array:3 [ "identificador" => "bib0470" "etiqueta" => "40" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "F.C. Arnett" 1 => "S.M. Edworthy" 2 => "D.A. Bloch" 3 => "D.J. McShane" 4 => "J.F. Fries" 5 => "N.S. Cooper" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Arthritis Rheum" "fecha" => "1988" "volumen" => "31" "paginaInicial" => "315" "paginaFinal" => "324" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3358796" "web" => "Medline" ] ] ] ] ] ] ] ] 40 => array:3 [ "identificador" => "bib0475" "etiqueta" => "41" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "2012 Brazilian Society of Rheumatology Consensus for the treatment of rheumatoid arthritis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "L.M. da Mota" 1 => "B.A. Cruz" 2 => "C.V. Brenol" 3 => "I.A. Pereira" 4 => "L.S. Rezende-Fronza" 5 => "M.B. Bertolo" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Rev Bras Reumatol" "fecha" => "2012" "volumen" => "52" "paginaInicial" => "152" "paginaFinal" => "174" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22460407" "web" => "Medline" ] ] ] ] ] ] ] ] 41 => array:3 [ "identificador" => "bib0480" "etiqueta" => "42" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Update of the Mexican College of Rheumatology guidelines for the pharmacologic treatment of rheumatoid arthritis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.H. Cardiel" 1 => "A. Diaz-Borjon" 2 => "E.M. Vazquez Del Mercado" 3 => "J.I. Gamez-Nava" 4 => "L.A. Barile Fabris" 5 => "T.C. Pacheco" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Reumatol Clin" "fecha" => "2014" "volumen" => "10" "paginaInicial" => "227" "paginaFinal" => "240" ] ] ] ] ] ] 42 => array:3 [ "identificador" => "bib0485" "etiqueta" => "43" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "XELJANZ® (tofacitinib) highlights of prescribing information" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "US Food and Drug Administration" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:1 [ "fecha" => "2017" ] ] ] ] ] ] 43 => array:3 [ "identificador" => "bib0490" "etiqueta" => "44" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tuberculosis and other opportunistic infections in tofacitinib-treated patients with rheumatoid arthritis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K.L. Winthrop" 1 => "S.H. Park" 2 => "A. Gul" 3 => "M.H. Cardiel" 4 => "J.J. Gomez-Reino" 5 => "Y. Tanaka" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/annrheumdis-2015-207319" "Revista" => array:6 [ "tituloSerie" => "Ann Rheum Dis" "fecha" => "2016" "volumen" => "75" "paginaInicial" => "1133" "paginaFinal" => "1138" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26318385" "web" => "Medline" ] ] ] ] ] ] ] ] 44 => array:3 [ "identificador" => "bib0495" "etiqueta" => "45" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effectiveness of recommendations to prevent reactivation of latent tuberculosis infection in patients treated with tumor necrosis factor antagonists" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "L. Carmona" 1 => "J.J. Gómez-Reino" 2 => "V. Rodríguez-Valverde" 3 => "D. Montero" 4 => "E. Pascual-Gómez" 5 => "E.M. Mola" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/art.21043" "Revista" => array:6 [ "tituloSerie" => "Arthritis Rheum" "fecha" => "2005" "volumen" => "52" "paginaInicial" => "1766" "paginaFinal" => "1772" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15934089" "web" => "Medline" ] ] ] ] ] ] ] ] 45 => array:3 [ "identificador" => "bib0500" "etiqueta" => "46" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Differences in reactivation of tuberculosis induced from anti-TNF treatments are based on bioavailability in granulomatous tissue" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Marino" 1 => "D. Sud" 2 => "H. Plessner" 3 => "P.L. Lin" 4 => "J. Chan" 5 => "J.L. Flynn" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pcbi.0030194" "Revista" => array:6 [ "tituloSerie" => "PLoS Comput Biol" "fecha" => "2007" "volumen" => "3" "paginaInicial" => "1909" "paginaFinal" => "1924" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17953477" "web" => "Medline" ] ] ] ] ] ] ] ] 46 => array:3 [ "identificador" => "bib0505" "etiqueta" => "47" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Safety of synthetic and biological DMARDs: a systematic literature review informing the 2013 update of the EULAR recommendations for management of rheumatoid arthritis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Ramiro" 1 => "C. Gaujoux-Viala" 2 => "J.L. Nam" 3 => "J.S. Smolen" 4 => "M. Buch" 5 => "L. Gossec" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/annrheumdis-2013-204575" "Revista" => array:6 [ "tituloSerie" => "Ann Rheum Dis" "fecha" => "2014" "volumen" => "73" "paginaInicial" => "529" "paginaFinal" => "535" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24401994" "web" => "Medline" ] ] ] ] ] ] ] ] 47 => array:3 [ "identificador" => "bib0510" "etiqueta" => "48" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tofacitinib for Treatment of Rheumatoid Arthritis (NDA 203214) Advisory Committee Meeting Briefing Document (NDA 203214)" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "FDA" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:1 [ "fecha" => "2012" ] ] ] ] ] ] 48 => array:3 [ "identificador" => "bib0515" "etiqueta" => "49" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Brazilian biologic registry: biobadaBrasil implementation process and preliminary results" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D.C. Titton" 1 => "I.G. Silveira" 2 => "P. Louzada-Junior" 3 => "A.L. Hayata" 4 => "H.M. Carvalho" 5 => "R. Ranza" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Rev Bras Reumatol" "fecha" => "2011" "volumen" => "51" "paginaInicial" => "152" "paginaFinal" => "160" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21584421" "web" => "Medline" ] ] ] ] ] ] ] ] 49 => array:3 [ "identificador" => "bib0520" "etiqueta" => "50" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Patient survival and safety with biologic therapy. Results of the Mexican National Registry Biobadamex 1.0" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "L. Ventura-Rios" 1 => "D. Banuelos-Ramirez" 2 => "M.C. Hernandez-Quiroz" 3 => "R.M. Robles-San" 4 => "F. Irazoque-Palazuelos" 5 => "M.V. Goycochea-Robles" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.reuma.2012.02.010" "Revista" => array:6 [ "tituloSerie" => "Reumatol Clin" "fecha" => "2012" "volumen" => "8" "paginaInicial" => "189" "paginaFinal" => "194" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22673388" "web" => "Medline" ] ] ] ] ] ] ] ] 50 => array:3 [ "identificador" => "bib0525" "etiqueta" => "51" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tofacitinib, an oral Janus kinase inhibitor, in the treatment of rheumatoid arthritis: open-label, long-term extension safety and efficacy up to 6 years" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Wollenhaupt" 1 => "J. Silverfield" 2 => "E.B. Lee" 3 => "S.P. Wood" 4 => "K. Terry" 5 => "H. Nakamura" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "Arthritis Rheumatol" "fecha" => "2014" "volumen" => "74" "paginaInicial" => "S375" ] ] ] ] ] ] 51 => array:3 [ "identificador" => "bib0530" "etiqueta" => "52" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Epidemiology in Latin America and the Caribbean: current situation and challenges" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S.M. Barreto" 1 => "J.J. Miranda" 2 => "J.P. Figueroa" 3 => "M.I. Schmidt" 4 => "S. Munoz" 5 => "P.P. Kuri-Morales" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/ije/dys017" "Revista" => array:6 [ "tituloSerie" => "Int J Epidemiol" "fecha" => "2012" "volumen" => "41" "paginaInicial" => "557" "paginaFinal" => "571" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22407860" "web" => "Medline" ] ] ] ] ] ] ] ] 52 => array:3 [ "identificador" => "bib0535" "etiqueta" => "53" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The neglected tropical diseases of Latin America and the Caribbean: a review of disease burden and distribution and a roadmap for control and elimination" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "P.J. Hotez" 1 => "M.E. Bottazzi" 2 => "C. Franco-Paredes" 3 => "S.K. Ault" 4 => "M.R. Periago" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pntd.0000300" "Revista" => array:5 [ "tituloSerie" => "PLoS Negl Trop Dis" "fecha" => "2008" "volumen" => "2" "paginaInicial" => "e300" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18820747" "web" => "Medline" ] ] ] ] ] ] ] ] 53 => array:3 [ "identificador" => "bib0540" "etiqueta" => "54" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Velez P, Jaller JJ, Otero W, Persand K, Mahgoub EY, Mebus C, et al. Tofacitinib, an oral Janus kinase inhibitor, in patients from Latin America with rheumatoid arthritis: pooled efficacy and safety analyses. Asociación Colombiana de Rheumatología, Medellín, Colombia, August 15–18, 2013." ] ] ] ] ] ] ] "agradecimientos" => array:1 [ 0 => array:4 [ "identificador" => "xack406795" "titulo" => "Acknowledgments" "texto" => "The authors would like to thank the patients, investigators and study teams involved in the studies included in this analysis. The authors would also like to thank Elaine Hoffman for providing statistical support. Medical writing support, under the direction of the authors, was provided by Rebecca Douglas, PhD, CMC Connect, a division of Complete Medical Communications Ltd, Macclesfield, UK and was funded by Pfizer Inc, New York, NY, USA in accordance with Good Publication Practice (GPP3) guidelines (Ann Intern Med 2015;163:461–464). This analysis was previously presented in poster form at Asociación Colombiana de Reumatología Medellín, Colombia, August 15–18, 2013.<a class="elsevierStyleCrossRef" href="#bib0540">54</a>" "vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/24444405/0000002500000004/v1_201905160826/S2444440519300329/v1_201905160826/en/main.assets" "Apartado" => array:4 [ "identificador" => "53648" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Original Investigation" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/24444405/0000002500000004/v1_201905160826/S2444440519300329/v1_201905160826/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2444440519300329?idApp=UINPBA00004N"]

Statistics

Original Investigation

Tofacitinib, an oral Janus kinase inhibitor, in patients from Colombia with rheumatoid arthritis: Pooled efficacy and safety analyses of data from phase III studies

Tofacitinib, un inhibidor oral de la janus kinasa, en pacientes colombianos con artritis reumatoide: análisis de eficacia y seguridad de los estudios de fase III

Patricia Véleza, Juan J. Jallerb, William J. Otero Escalantec, Erika G. Garcíad,1, Ricardo Rojoe, Douglass Chapmanf, Katherine Persandg,1, Giovanna A. Matizg,

Corresponding author

Giovannaalexandra.matiz@pfizer.com

Corresponding author.

a Reumatología, CIREI SAS, Bogotá, Colombia

b Centro de Reumatología y Ortopedia, Barranquilla, Colombia

c Departamento de Medicina Interna, Facultad de Salud, Universidad Industrial de Santander, Centro de Investigación Clínica Servimed E.U., Bucaramanga, Colombia

d Pfizer Inc, Collegeville, PA, USA

e Pfizer Inc, Groton, CT, USA

f Pfizer Inc, New York, NY, USA

g Pfizer Colombia, Bogotá, Colombia

Read

2189

Times
was read the article

425

Total PDF

1764

Total HTML

Share statistics

 array:23 [
  "pii" => "S2444440519300329"
  "issn" => "24444405"
  "doi" => "10.1016/j.rcreue.2018.08.002"
  "estado" => "S300"
  "fechaPublicacion" => "2018-10-01"
  "aid" => "199"
  "copyright" => "The Author&#40;s&#41;"
  "copyrightAnyo" => "2018"
  "documento" => "article"
  "crossmark" => 1
  "subdocumento" => "fla"
  "cita" => "Rev Colomb Reumatol. 2018;25:233-44"
  "abierto" => array:3 [
    "ES" => false
    "ES2" => false
    "LATM" => false
  ]
  "gratuito" => false
  "lecturas" => array:2 [
    "total" => 213
    "formatos" => array:3 [
      "EPUB" => 32
      "HTML" => 122
      "PDF" => 59
    ]
  ]
  "itemSiguiente" => array:19 [
    "pii" => "S2444440519300354"
    "issn" => "24444405"
    "doi" => "10.1016/j.rcreue.2018.08.003"
    "estado" => "S300"
    "fechaPublicacion" => "2018-10-01"
    "aid" => "200"
    "copyright" => "Asociaci&#243;n Colombiana de Reumatolog&#237;a"
    "documento" => "article"
    "crossmark" => 1
    "subdocumento" => "fla"
    "cita" => "Rev Colomb Reumatol. 2018;25:245-56"
    "abierto" => array:3 [
      "ES" => false
      "ES2" => false
      "LATM" => false
    ]
    "gratuito" => false
    "lecturas" => array:2 [
      "total" => 509
      "formatos" => array:3 [
        "EPUB" => 38
        "HTML" => 353
        "PDF" => 118
      ]
    ]
    "en" => array:13 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Original Investigation</span>"
      "titulo" => "Prevalence of rheumatic disease in Colombia according to the Colombian Rheumatology Association &#40;COPCORD&#41; strategy&#46; Prevalence study of rheumatic disease in Colombian population older than 18 years"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => array:2 [
        0 => "en"
        1 => "es"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "245"
          "paginaFinal" => "256"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "Prevalencia de la enfermedad reum&#225;tica en Colombia&#44; seg&#250;n estrategia COPCORD-Asociaci&#243;n Colombiana de Reumatolog&#237;a&#46; Estudio de prevalencia de enfermedad reum&#225;tica en poblaci&#243;n colombiana mayor de 18 a&#241;os"
        ]
      ]
      "contieneResumen" => array:2 [
        "en" => true
        "es" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:7 [
          "identificador" => "fig0025"
          "etiqueta" => "Fig&#46; 5"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr5.jpeg"
              "Alto" => 2857
              "Ancho" => 2395
              "Tamanyo" => 327773
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Quality of life and functional limitation assessed by EQ-5D-3L and HAQ-DI&#46;</p> <p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Panel A&#58; Functional ability assessed by HAQ&#44; the dots represent the mean of the instrument&#46; Panel B&#58; The lines represent the percentage of patients without pain of discomfort&#44; anxiety or depression&#44; or without mobility problems to perform daily living activities or personal care&#46; RA&#58; rheumatoid arthritis&#59; CHIKV&#58; chikungunya fever&#59; FM&#58; fibromyalgia&#59; SLE&#58; systemic lupus erythematosus&#59; MLBP&#58; mechanical low back pain&#59; OA&#58; osteoarthritis&#59; OTHER&#58; other non-rheumatic diseases&#59; RRPS&#58; regional appendicular pain syndrome&#59; HEALTHY&#58; healthy individuals&#59; SpA&#58; spondyloarthritis&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "John Londo&#241;o, Ingris Pel&#225;ez Ballestas, Francy Cuervo, Ignacio Angarita, Rodrigo Giraldo, Juan Camilo Rueda, Jes&#250;s Giovanny Ballesteros, Roberto Baquero, El&#237;as Forero, Mario Cardiel, Eugenia Saldarriaga, Andr&#233;s V&#225;squez, Sof&#237;a Arias, Lina Valero, Camilo Gonz&#225;lez, Javier Ram&#237;rez, Carlos Toro, Ana Mar&#237;a Santos"
          "autores" => array:18 [
            0 => array:2 [
              "nombre" => "John"
              "apellidos" => "Londo&#241;o"
            ]
            1 => array:2 [
              "nombre" => "Ingris"
              "apellidos" => "Pel&#225;ez Ballestas"
            ]
            2 => array:2 [
              "nombre" => "Francy"
              "apellidos" => "Cuervo"
            ]
            3 => array:2 [
              "nombre" => "Ignacio"
              "apellidos" => "Angarita"
            ]
            4 => array:2 [
              "nombre" => "Rodrigo"
              "apellidos" => "Giraldo"
            ]
            5 => array:2 [
              "nombre" => "Juan Camilo"
              "apellidos" => "Rueda"
            ]
            6 => array:2 [
              "nombre" => "Jes&#250;s Giovanny"
              "apellidos" => "Ballesteros"
            ]
            7 => array:2 [
              "nombre" => "Roberto"
              "apellidos" => "Baquero"
            ]
            8 => array:2 [
              "nombre" => "El&#237;as"
              "apellidos" => "Forero"
            ]
            9 => array:2 [
              "nombre" => "Mario"
              "apellidos" => "Cardiel"
            ]
            10 => array:2 [
              "nombre" => "Eugenia"
              "apellidos" => "Saldarriaga"
            ]
            11 => array:2 [
              "nombre" => "Andr&#233;s"
              "apellidos" => "V&#225;squez"
            ]
            12 => array:2 [
              "nombre" => "Sof&#237;a"
              "apellidos" => "Arias"
            ]
            13 => array:2 [
              "nombre" => "Lina"
              "apellidos" => "Valero"
            ]
            14 => array:2 [
              "nombre" => "Camilo"
              "apellidos" => "Gonz&#225;lez"
            ]
            15 => array:2 [
              "nombre" => "Javier"
              "apellidos" => "Ram&#237;rez"
            ]
            16 => array:2 [
              "nombre" => "Carlos"
              "apellidos" => "Toro"
            ]
            17 => array:2 [
              "nombre" => "Ana Mar&#237;a"
              "apellidos" => "Santos"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "Traduccion" => array:1 [
      "es" => array:9 [
        "pii" => "S0121812318300951"
        "doi" => "10.1016/j.rcreu.2018.08.003"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => false
          "ES2" => false
          "LATM" => false
        ]
        "gratuito" => false
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "es"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0121812318300951?idApp=UINPBA00004N"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2444440519300354?idApp=UINPBA00004N"
    "url" => "/24444405/0000002500000004/v1_201905160826/S2444440519300354/v1_201905160826/en/main.assets"
  ]
  "itemAnterior" => array:19 [
    "pii" => "S2444440519300287"
    "issn" => "24444405"
    "doi" => "10.1016/j.rcreue.2019.04.003"
    "estado" => "S300"
    "fechaPublicacion" => "2018-10-01"
    "aid" => "193"
    "copyright" => "Asociaci&#243;n Colombiana de Reumatolog&#237;a"
    "documento" => "article"
    "crossmark" => 1
    "subdocumento" => "fla"
    "cita" => "Rev Colomb Reumatol. 2018;25:228-32"
    "abierto" => array:3 [
      "ES" => false
      "ES2" => false
      "LATM" => false
    ]
    "gratuito" => false
    "lecturas" => array:2 [
      "total" => 239
      "formatos" => array:3 [
        "EPUB" => 37
        "HTML" => 127
        "PDF" => 75
      ]
    ]
    "en" => array:13 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Original Investigation</span>"
      "titulo" => "Literature analysis of economic aspects of rheumatoid arthritis"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => array:2 [
        0 => "en"
        1 => "es"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "228"
          "paginaFinal" => "232"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "An&#225;lisis bibliom&#233;trico de temas econ&#243;micos en artritis reumatoide"
        ]
      ]
      "contieneResumen" => array:2 [
        "en" => true
        "es" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:7 [
          "identificador" => "fig0010"
          "etiqueta" => "Fig&#46; 2"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr2.jpeg"
              "Alto" => 1212
              "Ancho" => 1508
              "Tamanyo" => 116525
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Distribution of countries of origin of the identified articles&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Melany Santrich Sotomayor, Mar&#237;a Eugenia Casanova, Jos&#233; Mauricio Ocampo"
          "autores" => array:3 [
            0 => array:2 [
              "nombre" => "Melany"
              "apellidos" => "Santrich Sotomayor"
            ]
            1 => array:2 [
              "nombre" => "Mar&#237;a Eugenia"
              "apellidos" => "Casanova"
            ]
            2 => array:2 [
              "nombre" => "Jos&#233; Mauricio"
              "apellidos" => "Ocampo"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "Traduccion" => array:1 [
      "es" => array:9 [
        "pii" => "S0121812318300884"
        "doi" => "10.1016/j.rcreu.2018.07.003"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => false
          "ES2" => false
          "LATM" => false
        ]
        "gratuito" => false
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "es"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0121812318300884?idApp=UINPBA00004N"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2444440519300287?idApp=UINPBA00004N"
    "url" => "/24444405/0000002500000004/v1_201905160826/S2444440519300287/v1_201905160826/en/main.assets"
  ]
  "en" => array:22 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">Original Investigation</span>"
    "titulo" => "Tofacitinib&#44; an oral Janus kinase inhibitor&#44; in patients from Colombia with rheumatoid arthritis&#58; Pooled efficacy and safety analyses of data from phase III studies"
    "tieneTextoCompleto" => true
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "233"
        "paginaFinal" => "244"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "Patricia V&#233;lez, Juan J&#46; Jaller, William J&#46; Otero Escalante, Erika G&#46; Garc&#237;a, Ricardo Rojo, Douglass Chapman, Katherine Persand, Giovanna A&#46; Matiz"
        "autores" => array:8 [
          0 => array:3 [
            "nombre" => "Patricia"
            "apellidos" => "V&#233;lez"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
          1 => array:3 [
            "nombre" => "Juan J&#46;"
            "apellidos" => "Jaller"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
            ]
          ]
          2 => array:3 [
            "nombre" => "William J&#46;"
            "apellidos" => "Otero Escalante"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">c</span>"
                "identificador" => "aff0015"
              ]
            ]
          ]
          3 => array:3 [
            "nombre" => "Erika G&#46;"
            "apellidos" => "Garc&#237;a"
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">d</span>"
                "identificador" => "aff0020"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">1</span>"
                "identificador" => "fn0005"
              ]
            ]
          ]
          4 => array:3 [
            "nombre" => "Ricardo"
            "apellidos" => "Rojo"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">e</span>"
                "identificador" => "aff0025"
              ]
            ]
          ]
          5 => array:3 [
            "nombre" => "Douglass"
            "apellidos" => "Chapman"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">f</span>"
                "identificador" => "aff0030"
              ]
            ]
          ]
          6 => array:3 [
            "nombre" => "Katherine"
            "apellidos" => "Persand"
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">g</span>"
                "identificador" => "aff0035"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">1</span>"
                "identificador" => "fn0005"
              ]
            ]
          ]
          7 => array:4 [
            "nombre" => "Giovanna A&#46;"
            "apellidos" => "Matiz"
            "email" => array:1 [
              0 => "Giovannaalexandra.matiz@pfizer.com"
            ]
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">g</span>"
                "identificador" => "aff0035"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;</span>"
                "identificador" => "cor0005"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:7 [
          0 => array:3 [
            "entidad" => "Reumatolog&#237;a&#44; CIREI SAS&#44; Bogot&#225;&#44; Colombia"
            "etiqueta" => "a"
            "identificador" => "aff0005"
          ]
          1 => array:3 [
            "entidad" => "Centro de Reumatolog&#237;a y Ortopedia&#44; Barranquilla&#44; Colombia"
            "etiqueta" => "b"
            "identificador" => "aff0010"
          ]
          2 => array:3 [
            "entidad" => "Departamento de Medicina Interna&#44; Facultad de Salud&#44; Universidad Industrial de Santander&#44; Centro de Investigaci&#243;n Cl&#237;nica Servimed E&#46;U&#46;&#44; Bucaramanga&#44; Colombia"
            "etiqueta" => "c"
            "identificador" => "aff0015"
          ]
          3 => array:3 [
            "entidad" => "Pfizer Inc&#44; Collegeville&#44; PA&#44; USA"
            "etiqueta" => "d"
            "identificador" => "aff0020"
          ]
          4 => array:3 [
            "entidad" => "Pfizer Inc&#44; Groton&#44; CT&#44; USA"
            "etiqueta" => "e"
            "identificador" => "aff0025"
          ]
          5 => array:3 [
            "entidad" => "Pfizer Inc&#44; New York&#44; NY&#44; USA"
            "etiqueta" => "f"
            "identificador" => "aff0030"
          ]
          6 => array:3 [
            "entidad" => "Pfizer Colombia&#44; Bogot&#225;&#44; Colombia"
            "etiqueta" => "g"
            "identificador" => "aff0035"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor0005"
            "etiqueta" => "&#8270;"
            "correspondencia" => "<span class="elsevierStyleItalic">Corresponding author</span>&#46;"
          ]
        ]
      ]
    ]
    "titulosAlternativos" => array:1 [
      "es" => array:1 [
        "titulo" => "Tofacitinib&#44; un inhibidor oral de la janus kinasa&#44; en pacientes colombianos con artritis reumatoide&#58; an&#225;lisis de eficacia y seguridad de los estudios de fase III"
      ]
    ]
    "resumenGrafico" => array:2 [
      "original" => 0
      "multimedia" => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Fig&#46; 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 1365
            "Ancho" => 2493
            "Tamanyo" => 121279
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Mean &#40;SE&#41; DAS28-4&#40;ESR&#41; over time for the tofacitinib 5 and 10<span class="elsevierStyleHsp" style=""></span>mg BID groups in the efficacy subpopulation &#40;FAS&#44; observed&#41;&#46;</p> <p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">BID&#58; twice daily&#59; DAS28-4&#40;ESR&#41;&#58; Disease Activity Score-erythrocyte sedimentation rate&#59; FAS&#58; full analysis set&#59; SE&#58; standard error&#46;</p> <p id="spar0080" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">N</span> represents the numbers of patients with non-missing DAS28-4&#40;ESR&#41;&#46; Efficacy analyses were based on three studies&#58; ORAL Scan&#44; ORAL Solo and ORAL Sync&#46;</p>"
        ]
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Rheumatoid arthritis &#40;RA&#41; is a debilitating autoimmune disease that leads to chronic inflammation and destruction of the joints and surrounding tissues of the musculoskeletal system&#46; Conservative estimates suggest that the prevalence rates for RA in the Latin American population &#40;as a whole&#41; range from 0&#46;4&#37; to 1&#46;6&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">1</span></a> A recent review of the epidemiology of RA in Colombia used medical records data to estimate the disease prevalence in Colombia to be 0&#46;15&#37;&#44;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">2</span></a> and an analysis of RA prevalence specifically for African Colombians from Quibdo observed a period prevalence rate of 0&#46;01&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">3</span></a> However&#44; a report from 2005 administrative sources estimated an overall Colombian prevalence of 0&#46;9&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">4</span></a> These low and varying prevalence rates may be due to genetic factors&#44; under-diagnosis and reduced access to treatment&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Consistent with European and US guidelines&#44;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">5&#44;6</span></a> Latin American specific guidelines &#40;Pan-American League of Associations for Rheumatology &#91;PANLAR&#93; and Grupo Latinoamericano de Estudio de Artritis Reumatoide &#91;GLADAR&#93;&#41; state that RA treatment should control inflammation&#44; minimize joint destruction and radiographic progression&#44; preserve functional and work capabilities and improve quality of life&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">7</span></a> However&#44; clinical management of RA in Latin American countries is subject to several challenges&#46; For example&#44; patient referral to specialist rheumatologists may be restricted or delayed&#44; access to cost-effective medication&#44; medical resources and public health services may be limited&#44; and there is a lack of public policies and education surrounding RA&#46;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">1&#44;7&#8211;10</span></a> Early diagnosis and treatment is important for slowing the structural progression of RA<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">11</span></a>&#59; however&#44; in a survey of Colombian rheumatologists&#44; 48&#46;6&#37; of respondents considered early RA to represent the first 3 months after onset of symptoms&#44; yet 54&#46;5&#37; believed that patients were not referred to specialists until between 3 and 6 months after symptom onset&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">12</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">For patients with RA in Colombia&#44; first-line treatment generally consists of conventional synthetic disease-modifying antirheumatic drugs &#40;csDMARDs&#41;&#44; followed by biologic disease-modifying antirheumatic drugs &#40;bDMARDs&#41;&#44; such as tumor necrosis factor inhibitors&#44; for patients who do not show an adequate response to initial treatment&#46;<a class="elsevierStyleCrossRefs" href="#bib0335"><span class="elsevierStyleSup">13&#8211;16</span></a> Screening for latent TB prior to initiation of bDMARDs is recommended in Latin American guidelines&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">7</span></a> As the incidence of Mycobacterium tuberculosis &#40;TB&#41; in Colombia is intermediate at 31 &#40;range 24&#8211;39&#41; cases per 100&#44;000 population&#59; both screening and monitoring for occurrence of TB during treatment is important in the Colombian patient population&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">17</span></a> In Colombia&#44; tofacitinib is recommended in adult patients with RA after failure to csDMARDs or biologic therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">16</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Although bDMARDs have not previously been commonly prescribed in Colombia&#44;<a class="elsevierStyleCrossRefs" href="#bib0280"><span class="elsevierStyleSup">2&#44;12</span></a> a recent retrospective study has shown an increasing number of prescriptions for bDMARDs among the study cohort of patients with RA&#44; with more than one-quarter receiving bDMARDs by the end of the study&#44; with etanercept and abatacept the most frequently used&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">15</span></a> In the Colombian patient population&#44; infliximab and adalimumab have previously been shown to improve functional capacity and quality of life in patients with refractory RA&#46;<a class="elsevierStyleCrossRefs" href="#bib0360"><span class="elsevierStyleSup">18&#44;19</span></a> However&#44; traditionally&#44; the low prescription of bDMARDs may be a consequence of the high costs associated with bDMARDs&#44; and the requirement for close clinical and serologic monitoring of patients&#46; A recent Colombian cross-sectional study showed that from one-third to half of patients attending a specialized care clinic were in remission according to disease activity score &#40;DAS28 &#60;2&#46;6&#59; DAS erythrocyte sedimentation rate &#91;ESR&#93; 34&#46;1&#37; and DAS28 C-reactive protein &#91;CRP&#93; 49&#46;5&#37;&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">13</span></a> although it is important to note that acute phase reactant levels may not always reflect disease activity&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">20</span></a> A Colombian retrospective cohort analysis showed 42&#46;9&#37; of patients achieving remission defined as DAS28 &#8804;2&#46;6&#44;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">15</span></a> highlighting a requirement for alternative RA therapies&#46; Moreover&#44; although this remission rate may seem high&#44; remission rates using different parameters&#44; such as Routine Assessment of Patient Index Data &#40;RAPID&#41;&#44; Clinical Disease Activity Index &#40;CDAI&#41;&#44; Simplified Disease Activity Index &#40;SDAI&#41;&#44; often show lower remission rates&#46;<a class="elsevierStyleCrossRefs" href="#bib0375"><span class="elsevierStyleSup">21&#44;22</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA&#46; The efficacy and safety of tofacitinib 5 and 10<span class="elsevierStyleHsp" style=""></span>mg twice daily &#40;BID&#41; have been demonstrated in patients with moderately to severely active RA and various treatment histories in randomized global phase II<a class="elsevierStyleCrossRefs" href="#bib0385"><span class="elsevierStyleSup">23&#8211;28</span></a> and phase III<a class="elsevierStyleCrossRefs" href="#bib0415"><span class="elsevierStyleSup">29&#8211;34</span></a> studies of up to 24 months&#8217; duration&#44; and in long-term extension &#40;LTE&#41; studies with up to 114 months of observation&#46;<a class="elsevierStyleCrossRefs" href="#bib0445"><span class="elsevierStyleSup">35&#8211;37</span></a> Safety and efficacy of tofacitinib specifically in Latin American populations have been analyzed previously in Phase III and LTE studies&#44; due to differences in epidemiology and treatment guidelines compared with global populations&#46; <a class="elsevierStyleCrossRefs" href="#bib0460"><span class="elsevierStyleSup">38&#44;39</span></a> In this post hoc analysis&#44; the efficacy and safety of tofacitinib 5 and 10<span class="elsevierStyleHsp" style=""></span>mg BID was evaluated in a subpopulation of Colombian patients included in the global phase III studies in RA&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Patients</span><p id="par0030" class="elsevierStylePara elsevierViewall">This analysis included data from Colombian patients enrolled in four global phase III studies of tofacitinib for the treatment of RA&#46; Patient inclusion and exclusion criteria have previously been reported in detail for each individual study&#46;<a class="elsevierStyleCrossRefs" href="#bib0350"><span class="elsevierStyleSup">16&#44;29&#8211;31&#44;33</span></a> In summary&#44; eligible patients were aged &#8805;18 years and had a diagnosis of moderately to severely active RA based on American College of Rheumatology &#40;ACR&#41; 20&#47;50&#47;70 response rate criteria&#46;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">40</span></a> Patients were excluded if they had recent&#44; current or serious chronic infections&#59; active or inadequately treated latent TB infection&#59; history of recurrent herpes zoster&#44; disseminated herpes zoster&#44; or disseminated herpes simplex&#59; hepatitis B or C&#59; human immunodeficiency virus&#59; evidence or history of malignancy&#44; other than adequately treated or excised non-metastatic basal or squamous cell cancer of the skin&#44; or cervical carcinoma <span class="elsevierStyleItalic">in situ</span>&#59; and evidence or history of lymphoma or lymphoproliferative disease&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Study designs</span><p id="par0035" class="elsevierStylePara elsevierViewall">Data were analyzed from four phase III double-blind&#44; randomized&#44; controlled studies of 6&#8211;24 months&#8217; duration that included patients from Colombia&#58; ORAL Sync &#91;<a href="ctgov:NCT00856544">NCT00856544</a>&#59; 12 months&#93;&#44;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">30</span></a> ORAL Scan &#91;<a href="ctgov:NCT00847613">NCT00847613</a>&#59; 24 months&#93;&#44;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">31</span></a> ORAL Solo &#91;<a href="ctgov:NCT00814307">NCT00814307</a>&#59; 6 months&#93;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">29</span></a> and ORAL Start &#91;<a href="ctgov:NCT01039688">NCT01039688</a>&#59; 12-month data-cut&#44; study was ongoing&#44; database not locked&#93;&#46;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">33</span></a> These studies included patients who had previously had an inadequate response to methotrexate &#40;ORAL Scan&#41;&#44; or &#8805;1 bDMARD or csDMARD &#40;ORAL Sync and ORAL Solo&#41;&#46; Patients enrolled in ORAL Start were na&#239;ve to methotrexate treatment &#40;defined as no prior treatment or &#8804;3 weekly doses&#41;&#46; In ORAL Scan&#44; ORAL Sync and ORAL Solo&#44; patients were randomized to receive tofacitinib 5<span class="elsevierStyleHsp" style=""></span>mg BID&#44; tofacitinib 10<span class="elsevierStyleHsp" style=""></span>mg BID&#44; placebo advanced to tofacitinib 5<span class="elsevierStyleHsp" style=""></span>mg BID&#44; or placebo advanced to tofacitinib 10<span class="elsevierStyleHsp" style=""></span>mg BID&#46; In the ORAL Sync and ORAL Scan studies&#44; placebo patients who did not achieve ACR20 at Month 3 were advanced to tofacitinib treatment according to randomization&#46; All remaining placebo patients advanced to tofacitinib treatment at Month 6&#46; All placebo patients advanced to tofacitinib treatment at Month 3 in ORAL Solo&#46; In ORAL Start&#44; patients were randomized to receive tofacitinib 5<span class="elsevierStyleHsp" style=""></span>mg BID&#44; tofacitinib 10<span class="elsevierStyleHsp" style=""></span>mg BID&#44; or methotrexate 10<span class="elsevierStyleHsp" style=""></span>mg per week titrated to 20<span class="elsevierStyleHsp" style=""></span>mg per week over the course of 8 weeks&#44; and maintained for the duration of the study&#46; Study drug was administered either as monotherapy &#40;in ORAL Solo and ORAL Start&#41;&#44; or in combination with background methotrexate &#40;ORAL Scan&#41; or csDMARDs &#40;ORAL Sync&#41;&#46; Further information on study initiation&#44; completion dates and Principal Investigators is shown in <a class="elsevierStyleCrossRef" href="#sec0090">Supplementary Table 4</a>&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">All studies were conducted in accordance with the Declaration of Helsinki and the International Conference on Harmonisation Good Clinical Practice Guidelines&#44; and were approved by Institutional Review Boards and&#47;or Independent Ethics Committees at each of the investigational centers participating in the study&#46; All patients provided written informed consent&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Efficacy endpoints</span><p id="par0045" class="elsevierStylePara elsevierViewall">Efficacy endpoints assessed up to Month 24 included&#58; ACR20&#44; ACR50 and ACR70 response rates&#59; mean Disease Activity Score &#40;DAS&#41;28-4 &#40;erythrocyte sedimentation rate &#91;ESR&#93;&#41; scores&#59; and mean change from baseline in Health Assessment Questionnaire-Disability Index &#40;HAQ-DI&#41; scores&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Safety endpoints</span><p id="par0050" class="elsevierStylePara elsevierViewall">Endpoints included reporting of adverse events &#40;AEs&#41;&#44; serious AEs&#44; discontinuations due to AEs&#44; and mortality cases&#46; Malignancy events were adjudicated by an independent adjudication committee&#44; which carried out a blinded review of each biopsy case with at least two independent&#44; board-certified pathologists&#46; Major cardiovascular AEs and all deaths were adjudicated by a blinded&#44; independent&#44; external cardiovascular safety endpoint adjudication committee for all phase III studies&#46; Patients were screened for latent or untreated TB before enrollment&#44; in accordance with the protocol for patients using bDMARDs in other Latin American countries&#46;<a class="elsevierStyleCrossRefs" href="#bib0475"><span class="elsevierStyleSup">41&#44;42</span></a> All available safety data were analyzed up to Month 24&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Statistical analysis</span><p id="par0055" class="elsevierStylePara elsevierViewall">All efficacy and safety analyses were based on observed cases &#40;i&#46;e&#46; no imputation of missing values&#41; in the full analysis set &#40;FAS&#41;&#44; which included all patients who were randomized and received at least one dose of study treatment &#40;tofacitinib&#44; placebo or methotrexate&#41;&#46; Efficacy analyses were assessed using FAS pooled data from three studies &#40;ORAL Scan&#44; ORAL Solo and ORAL Sync&#41;&#46; Patients from ORAL Start were not included in efficacy analyses as they were a methotrexate-na&#239;ve population&#44; and therefore represented a different patient population versus the populations in the other three studies&#46; Efficacy data are reported for tofacitinib groups only&#44; as patient numbers in the placebo and methotrexate groups were too low for meaningful comparison&#46; Safety analyses were performed on FAS data pooled from all four studies &#40;ORAL Scan&#44; ORAL Solo&#44; ORAL Sync and ORAL Start&#41;&#46; Despite low patient numbers in some groups&#44; safety data are reported for all groups for completeness&#46; All analyses were descriptive in nature&#44; and general trends were described&#46; Due to small sample sizes&#44; no statistical hypothesis testing was performed&#59; therefore&#44; all differences described in the Results section refer to numerical differences only&#46;</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Results</span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Patients</span><p id="par0060" class="elsevierStylePara elsevierViewall">In total&#44; 77 Colombian patients from three studies &#40;ORAL Scan&#44; ORAL Solo and ORAL Sync&#41; were included in the efficacy analysis&#44; and 125 Colombian patients from four studies &#40;ORAL Scan&#44; ORAL Solo&#44; ORAL Sync and ORAL Start&#41; were included in the safety analyses&#46; Baseline demographics and characteristics were generally similar across treatment groups within the efficacy and safety analyses populations&#44; although in the safety population the mean duration of RA was higher in the placebo groups and both the mean duration of RA and mean age were lower in the methotrexate-treated groups versus the other treatment groups &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Efficacy</span><p id="par0065" class="elsevierStylePara elsevierViewall">At Month 1&#44; ACR20 response rates for both tofacitinib 5<span class="elsevierStyleHsp" style=""></span>mg BID &#40;75&#46;0&#37;&#41; and tofacitinib 10<span class="elsevierStyleHsp" style=""></span>mg BID &#40;74&#46;2&#37;&#41; were similar&#46; Between Month 3 and Month 9&#44; ACR20 responses ranged from 66&#46;7&#8211;to 74&#46;2&#37; and 76&#46;7&#8211;86&#46;2&#37; for tofacitinib 5 and 10<span class="elsevierStyleHsp" style=""></span>mg BID&#44; respectively &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>A and <a class="elsevierStyleCrossRef" href="#sec0090">Supplementary Table 1</a>&#41;&#46; By Month 12&#44; ACR20 response rates for both tofacitinib 5 and 10<span class="elsevierStyleHsp" style=""></span>mg BID groups improved further &#40;82&#46;4&#37; and 93&#46;8&#37;&#44; respectively&#41;&#46; Therefore&#44; although patient numbers reduced after Month 6&#44; ACR20 response rates across all treatment groups were generally sustained to Month 12 &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>A and <a class="elsevierStyleCrossRef" href="#sec0090">Supplementary Table 1</a>&#41;&#46; After Month 12&#44; patient numbers were low&#59; however&#44; improvements in ACR20 responses appeared to be generally sustained through Month 24 &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>A and <a class="elsevierStyleCrossRef" href="#sec0090">Supplementary Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">ACR50 response improved over time for both tofacitinib 5 and 10<span class="elsevierStyleHsp" style=""></span>mg BID groups from Month 1 &#40;21&#46;9&#37; and 41&#46;9&#37;&#44; respectively&#41;&#44; and from Month 3 &#40;48&#46;5&#37; and 53&#46;3&#37;&#44; respectively&#41; through to Month 12 &#40;52&#46;9&#37; and 75&#46;0&#37;&#44; respectively&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>B and <a class="elsevierStyleCrossRef" href="#sec0090">Supplementary Table 1</a>&#41;&#46; Tofacitinib 10<span class="elsevierStyleHsp" style=""></span>mg BID appeared to show higher ACR50 responses than tofacitinib 5<span class="elsevierStyleHsp" style=""></span>mg BID&#44; although no formal statistical analysis was performed&#46; From Month 12 to Month 24&#44; patient numbers were low for both tofacitinib 5 and 10<span class="elsevierStyleHsp" style=""></span>mg BID groups&#44; and ACR50 responses ranged from 33&#46;3&#8211;83&#46;3&#37; and 66&#46;7&#8211;83&#46;3&#37;&#44; respectively &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>B and <a class="elsevierStyleCrossRef" href="#sec0090">SupplementaryTable 1</a>&#41;&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Similarly&#44; ACR70 response rates improved over time for both tofacitinib 5 and 10<span class="elsevierStyleHsp" style=""></span>mg BID groups from Month 1 &#40;3&#46;1&#37; and 9&#46;7&#37;&#44; respectively&#41;&#44; and from Month 3 &#40;21&#46;2&#37; and 20&#46;0&#37;&#44; respectively&#41; through to Month 12 &#40;41&#46;2&#37; and 43&#46;8&#37;&#44; respectively&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>C and <a class="elsevierStyleCrossRef" href="#sec0090">Supplementary Table 1</a>&#41;&#46; ACR70 responses were comparable among both tofacitinib groups from Month 3 to Month 12&#46; From Month 12 to Month 24&#44; ACR70 responses varied over time with tofacitinib 5<span class="elsevierStyleHsp" style=""></span>mg BID &#40;0&#8211;50&#46;0&#37;&#41;&#44; and were generally sustained with tofacitinib 10<span class="elsevierStyleHsp" style=""></span>mg BID &#40;28&#46;6&#8211;44&#46;4&#37;&#41;&#59; however&#44; patient numbers for these time points were low &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>C and <a class="elsevierStyleCrossRef" href="#sec0090">Supplementary Table 1</a>&#41;&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Mean DAS28-4&#40;ESR&#41; steadily improved over time for both tofacitinib 5 and 10<span class="elsevierStyleHsp" style=""></span>mg BID groups from baseline &#40;6&#46;3 and 6&#46;2&#44; respectively&#41;&#44; to Month 1 &#40;4&#46;6 and 4&#46;0&#44; respectively&#41;&#44; to Month 3 &#40;4&#46;3 and 3&#46;9&#44; respectively&#41; and through to Month 12 &#40;3&#46;7 and 2&#46;8&#44; respectively&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a> and <a class="elsevierStyleCrossRef" href="#sec0090">Supplementary Table 2</a>&#41;&#46; Although patient numbers were low after Month 12&#44; improvements in mean DAS28-4&#40;ESR&#41; appeared to be generally sustained through to Month 24 &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a> and <a class="elsevierStyleCrossRef" href="#sec0090">Supplementary Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">Improvements from baseline in mean HAQ-DI scores were observed for both tofacitinib 5 and 10<span class="elsevierStyleHsp" style=""></span>mg BID groups as early as Month 1 &#40;&#8722;0&#46;4 and &#8722;0&#46;9&#44; respectively&#41;&#44; and were sustained over time to Month 3 &#40;&#8722;0&#46;6 and &#8722;0&#46;9&#41; through to Month 12 &#40;&#8722;1&#46;0 and &#8722;0&#46;8&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#44; <a class="elsevierStyleCrossRef" href="#sec0090">Supplementary Table 3</a>&#41;&#46; Although patient numbers were low after Month 12&#44; improvements in mean HAQ-DI scores appeared to be generally sustained through to Month 24 &#40;&#8722;0&#46;9 and &#8722;1&#46;0&#44; respectively&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Safety</span><p id="par0090" class="elsevierStylePara elsevierViewall">In total&#44; 15 patients receiving tofacitinib treatment discontinued from the studies&#59; 13 of these discontinuations were considered unrelated to study drug&#44; and two patients &#40;one each in the tofacitinib 5 and 10<span class="elsevierStyleHsp" style=""></span>mg BID groups&#41; discontinued due to AEs related to study drug &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; No serious AEs or deaths were reported in any treatment group&#46; A higher proportion of patients reported treatment-emergent AEs &#40;TEAEs&#41; after Month 6 compared with the Month 0&#8211;3 and Month 3&#8211;6 treatment periods &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0095" class="elsevierStylePara elsevierViewall">During the first 3 months of treatment&#44; the most frequently reported TEAEs were anemia for the placebo and tofacitinib 5<span class="elsevierStyleHsp" style=""></span>mg BID groups&#44; and anemia and urinary tract infection for the tofacitinib 10<span class="elsevierStyleHsp" style=""></span>mg BID group&#59; no TEAEs were reported in the methotrexate group &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; One case each of hypotension and hematoma were with tofacitinib 5<span class="elsevierStyleHsp" style=""></span>mg BID and one case of hypertensive crisis was reported with tofacitinib 10<span class="elsevierStyleHsp" style=""></span>mg BID&#46; Between Months 3 and 6&#44; the most frequently reported TEAEs were hematuria&#44; headache and increased blood creatine phosphokinase with tofacitinib 5<span class="elsevierStyleHsp" style=""></span>mg BID&#44; and anemia with tofacitinib 10<span class="elsevierStyleHsp" style=""></span>mg BID&#46; One case of non-melanoma skin cancer &#40;NMSC&#59; basal cell carcinoma&#41; malignancy was reported in the tofacitinib 10<span class="elsevierStyleHsp" style=""></span>mg BID group between Months 3 and 6&#46; No TEAEs were reported in patients receiving methotrexate&#44; and no particular TEAE was more frequent in the placebo group&#46; Post-Month 6&#44; the most frequently reported TEAEs for tofacitinib-treated patients were anemia&#44; headache&#44; influenza and increased blood creatine phosphokinase&#59; no particular TEAE was more frequent in the methotrexate group &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; Differences were observed between AEs reported for patients receiving tofacitinib 5 or 10<span class="elsevierStyleHsp" style=""></span>mg BID post-6 months&#44; with a higher number of reported headaches&#44; influenza and gastrointestinal disorders &#40;upper abdominal pain and dyspepsia&#41; in patients receiving tofacitinib 10<span class="elsevierStyleHsp" style=""></span>mg BID compared with those receiving tofacitinib 5<span class="elsevierStyleHsp" style=""></span>mg BID&#46; Post-Month 6&#44; there was one other reported case of NMSC &#40;basal cell carcinoma&#41; malignancy in the tofacitinib 10<span class="elsevierStyleHsp" style=""></span>mg BID group&#44; and a single reported case of herpes zoster in the tofacitinib 5<span class="elsevierStyleHsp" style=""></span>mg BID group&#59; no other cases of herpes zoster were reported&#46; One case each of tachycardia was reported with tofacitinib 5 and 10<span class="elsevierStyleHsp" style=""></span>mg BID&#44; respectively&#46; There were no reported cases of TB&#44; opportunistic infections&#44; serious infections or gastrointestinal perforations&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Discussion</span><p id="par0100" class="elsevierStylePara elsevierViewall">This post hoc analysis of the efficacy and safety of tofacitinib in Colombian patients with RA demonstrated that tofacitinib 5<span class="elsevierStyleHsp" style=""></span>mg BID and tofacitinib 10<span class="elsevierStyleHsp" style=""></span>mg BID reduced the signs and symptoms of RA&#44; as measured by ACR20&#44; ACR50 and ACR70 response rates and mean DAS28-4&#40;ESR&#41;&#44; and improved physical function&#44; as measured by mean change from baseline in HAQ-DI&#46; Although patient numbers were low post-Month 12&#44; efficacy improvements were generally sustained through to Month 24 in the tofacitinib 5 and 10<span class="elsevierStyleHsp" style=""></span>mg BID groups&#46; Demographics were generally similar among the Colombian populations studied here and the global data&#44; with the exception of race&#44; where the majority of Colombian patients were non-white&#59; however&#44; additional analysis of this category was not conducted&#46; Mean RA duration was generally slightly shorter &#40;excluding placebo which was higher&#41; and HAQ-DI was generally higher in the data reported here&#44; compared with global data for these studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0415"><span class="elsevierStyleSup">29&#8211;34&#44;38&#44;39</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">Similar improvements in efficacy outcomes at Month 3 were observed for Colombian patients receiving tofacitinib 5<span class="elsevierStyleHsp" style=""></span>mg BID and tofacitinib 10<span class="elsevierStyleHsp" style=""></span>mg BID&#44; compared with the Latin American population in tofacitinib phase III studies and generally similar efficacy outcomes compared with LTE studies&#46;<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">38</span></a> The efficacy analyses presented here showed that ACR response rates&#44; change from baseline in HAQ-DI&#44; and mean DAS28-4&#40;ESR&#41; were also generally similar compared with the global phase III RA population&#46;<a class="elsevierStyleCrossRefs" href="#bib0415"><span class="elsevierStyleSup">29&#8211;34&#44;38</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">Unlike many bDMARDs&#44; which require subcutaneous or intravenous administration&#44; tofacitinib is administered orally&#46; This may be particularly beneficial in Colombia&#44; where some patients may not have easy access to resources related to transportation&#44; storage and administration of these medications&#46; However&#44; patients receiving tofacitinib do require routine monitoring of neutrophils&#44; lymphocytes&#44; hemoglobin&#44; liver enzymes and lipids&#44; as well as baseline screening for TB and viral hepatitis&#46; <a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">43</span></a> Our results for Colombian patients with RA support the global findings that tofacitinib could provide an effective oral alternative to bDMARDs&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">There were no reported cases of serious AEs&#44; serious infections&#44; or deaths in any of the treatment groups&#44; and the overall safety profile of tofacitinib was generally similar between the Colombian subpopulation and both the global phase III RA population<a class="elsevierStyleCrossRefs" href="#bib0415"><span class="elsevierStyleSup">29&#8211;34</span></a> and the Latin American population&#46;<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">38</span></a> However&#44; in interpreting these findings it is important to acknowledge that the global and Latin American populations included a larger number of patients&#44; with greater total tofacitinib exposure analyzed&#44; compared with the Colombian subpopulation&#46; Two cases of NMSC malignancies were reported in the tofacitinib 10<span class="elsevierStyleHsp" style=""></span>mg BID group&#46; No cases of lymphoma&#44; or lymphoproliferative disorders were reported in Colombian patients&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">No cases of TB were reported in this Colombian subpopulation&#44; which is consistent with the low incidence reported in the Latin American and global phase III and LTE populations&#46; <a class="elsevierStyleCrossRefs" href="#bib0415"><span class="elsevierStyleSup">29-34&#44;38&#44;39&#44;44</span></a> It is important to note that patients enrolled into tofacitinib clinical trials were screened for latent or untreated TB before enrollment&#44; and it is recommended that all patients &#40;including those from countries where TB is not endemic&#41; should be screened for TB before initiating tofacitinib treatment&#44; as is already the case for patients using bDMARDs in other Latin American countries&#46;<a class="elsevierStyleCrossRefs" href="#bib0475"><span class="elsevierStyleSup">41&#44;42</span></a> Furthermore&#44; previous reports have indicated that the risk of developing TB while receiving immunosuppressant therapy varies according to the background TB rate in the underlying population&#46;<a class="elsevierStyleCrossRefs" href="#bib0490"><span class="elsevierStyleSup">44&#8211;47</span></a> The latest World Health Organization Global Tuberculosis Report listed incidence of TB in Colombia as intermediate&#44; therefore monitoring for TB as a possible AE of special interest was important in this population&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">17</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">Overall&#44; fewer AEs&#44; serious AEs and deaths were reported for the Colombian subpopulation compared with the Latin American and global populations&#59; however&#44; this is most likely the result of the small sample size in the Colombian subpopulation&#46;<a class="elsevierStyleCrossRefs" href="#bib0415"><span class="elsevierStyleSup">29&#8211;34&#44;38&#44;39</span></a> Investigator-reported increases in blood creatine phosphokinase were observed in some patients receiving tofacitinib in this Colombian subpopulation&#59; however&#44; proportions of events were no higher than in the long-term extension studies in the Latin American population&#46;<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">38</span></a> Similarly&#44; throughout the entire global RA program generally&#44; mean values for serum creatine phosphokinase remained within normal reference ranges&#46;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">48</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">Treatment with bDMARDs can increase the risk of infections and infestations compared with csDMARDs in patients in Latin American countries&#46;<a class="elsevierStyleCrossRefs" href="#bib0515"><span class="elsevierStyleSup">49&#44;50</span></a> No opportunistic infections or serious infections were reported in this analysis of Colombian patients&#44; and there was one case of non-serious herpes zoster in the tofacitinib 5<span class="elsevierStyleHsp" style=""></span>mg BID group&#59; however&#44; it should be noted that the comparatively low Colombian patient numbers may not enable generalization to the wider population&#46; In the global tofacitinib studies&#44; increased rates of herpes zoster were observed with tofacitinib treatment compared with placebo&#44; but reports of complicated herpes zoster events have been rare for tofacitinib-treated patients in longer-term studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0415"><span class="elsevierStyleSup">29&#8211;35&#44;51</span></a> Therefore&#44; there were no cases of TB&#44; opportunistic infection&#44; gastrointestinal perforation&#44; or serious cardiovascular AEs&#44; and few cases of herpes zoster or malignancies were reported in Colombian patients receiving tofacitinib in these phase III studies&#46; However&#44; it remains important to routinely monitor patients for these AEs&#44; as is already recommended in Colombian guidelines for other immunosuppressant therapies&#46;<a class="elsevierStyleCrossRefs" href="#bib0340"><span class="elsevierStyleSup">14&#44;16</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">With the exception of ORAL Start&#44; in which patients were MTX-na&#239;ve&#44; the patient populations among ORAL Scan&#44; ORAL Solo and ORAL Sync were generally very similar and were DMARD-IR&#46; Therefore&#44; this post hoc analysis was somewhat limited by the use of pooled data&#44; which can provide a heterogeneous patient population&#46; Moreover&#44; there were some differences in designs and methodologies of the phase III studies included in this analysis&#46; As such&#44; efficacy analyses included patients from ORAL Scan&#44; ORAL Solo and ORAL Sync only&#44; as patients in ORAL Start were methotrexate-na&#239;ve&#44; and represented a different patient population that was not directly comparable&#46; A greater proportion of Colombian patients were identified as non-white compared with the global populations&#59; however&#44; further investigation of race within the non-white listing category was not conducted&#46; At all time points&#44; patient numbers in the placebo and methotrexate groups were too low to allow meaningful comparison to be made with the tofacitinib groups&#44; and therefore the exclusion of these groups from efficacy analyses limits the interpretation of the findings&#46; For completeness&#44; placebo and methotrexate groups were included in the safety analysis&#59; however&#44; the placebo group was smaller and had shorter exposure than the tofacitinib groups&#44; which limits meaningful between group comparisons&#46; Another important limitation of this post hoc analysis is the low patient numbers for all groups post-Month 12&#46; Due to these low patient numbers&#44; efficacy outcomes for tofacitinib groups post-Month 12&#44; and any safety differences between active treatment and placebo post-Month 12&#44; should be interpreted with caution&#46; Due to the small sample sizes of this analysis of the Colombian sub-population&#44; no formal statistical analyses were conducted&#46; Also analyses were not powered to identify differences in efficacy or safety between treatment groups&#44; therefore&#44; conclusions are not definitive and are based on descriptive analyses only&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Conclusion</span><p id="par0140" class="elsevierStylePara elsevierViewall">Two studies observed that from one-third to half of patients with RA in Colombia may be achieving remission&#59;<a class="elsevierStyleCrossRefs" href="#bib0335"><span class="elsevierStyleSup">13&#44;15</span></a> as such&#44; there may be an unmet clinical need in Colombia for new RA therapies that can improve treatment outcomes for patients who have an inadequate response to csDMARDs and bDMARDs&#46; Our results suggest that tofacitinib 5<span class="elsevierStyleHsp" style=""></span>mg BID and tofacitinib 10<span class="elsevierStyleHsp" style=""></span>mg BID were efficacious over 12 months &#40;Month 24 data also presented&#41; for the treatment of RA in Colombian patients in phase III studies&#59; this was consistent with the findings from the global phase III and Latin American populations&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">The data presented here for the Colombian sub-population suggest that there are no major differences in terms of efficacy or safety compared with patients from Latin American or global populations&#46; Therefore&#44; no significant differential factor emerged between the Colombian populations and other populations&#44; which may be important when considering that incidences of some infections and neglected tropical diseases are more frequent in Latin American countries&#46;<a class="elsevierStyleCrossRefs" href="#bib0530"><span class="elsevierStyleSup">52&#44;53</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">Both tofacitinib doses demonstrated a manageable safety profile in the Colombian subpopulation&#46; Overall&#44; our results support the favorable benefit-risk of tofacitinib as an oral alternative to bDMARDs for the treatment of patients with RA in Colombia&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Funding</span><p id="par0155" class="elsevierStylePara elsevierViewall">This study was funded by Pfizer Inc&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Author roles and contributions</span><p id="par0160" class="elsevierStylePara elsevierViewall">All authors meet the criteria for authorship and have approved the final article&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Conflict of interest</span><p id="par0165" class="elsevierStylePara elsevierViewall">P V&#233;lez and W Otero Escalante have no conflicts of interest to declare&#46; JJ Jaller has no conflicts of interest to declare&#46; EG Garc&#237;a and K Persand were employees and shareholders of Pfizer Inc at the time the studies were conducted&#46; R Rojo&#44; D Chapman&#44; and G Matiz are employees of Pfizer Inc&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:14 [
        0 => array:3 [
          "identificador" => "xres1190600"
          "titulo" => "Abstract"
          "secciones" => array:5 [
            0 => array:2 [
              "identificador" => "abst0005"
              "titulo" => "Introduction"
            ]
            1 => array:2 [
              "identificador" => "abst0010"
              "titulo" => "Objective"
            ]
            2 => array:2 [
              "identificador" => "abst0015"
              "titulo" => "Methods"
            ]
            3 => array:2 [
              "identificador" => "abst0020"
              "titulo" => "Results"
            ]
            4 => array:2 [
              "identificador" => "abst0025"
              "titulo" => "Conclusions"
            ]
          ]
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec1109938"
          "titulo" => "Keywords"
        ]
        2 => array:3 [
          "identificador" => "xres1190601"
          "titulo" => "Resumen"
          "secciones" => array:5 [
            0 => array:2 [
              "identificador" => "abst0030"
              "titulo" => "Introducci&#243;n"
            ]
            1 => array:2 [
              "identificador" => "abst0035"
              "titulo" => "Objetivo"
            ]
            2 => array:2 [
              "identificador" => "abst0040"
              "titulo" => "M&#233;todos"
            ]
            3 => array:2 [
              "identificador" => "abst0045"
              "titulo" => "Resultados"
            ]
            4 => array:2 [
              "identificador" => "abst0050"
              "titulo" => "Conclusiones"
            ]
          ]
        ]
        3 => array:2 [
          "identificador" => "xpalclavsec1109939"
          "titulo" => "Palabras clave"
        ]
        4 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
        ]
        5 => array:3 [
          "identificador" => "sec0010"
          "titulo" => "Methods"
          "secciones" => array:5 [
            0 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Patients"
            ]
            1 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "Study designs"
            ]
            2 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Efficacy endpoints"
            ]
            3 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "Safety endpoints"
            ]
            4 => array:2 [
              "identificador" => "sec0035"
              "titulo" => "Statistical analysis"
            ]
          ]
        ]
        6 => array:3 [
          "identificador" => "sec0040"
          "titulo" => "Results"
          "secciones" => array:3 [
            0 => array:2 [
              "identificador" => "sec0045"
              "titulo" => "Patients"
            ]
            1 => array:2 [
              "identificador" => "sec0050"
              "titulo" => "Efficacy"
            ]
            2 => array:2 [
              "identificador" => "sec0055"
              "titulo" => "Safety"
            ]
          ]
        ]
        7 => array:2 [
          "identificador" => "sec0060"
          "titulo" => "Discussion"
        ]
        8 => array:2 [
          "identificador" => "sec0065"
          "titulo" => "Conclusion"
        ]
        9 => array:2 [
          "identificador" => "sec0070"
          "titulo" => "Funding"
        ]
        10 => array:2 [
          "identificador" => "sec0075"
          "titulo" => "Author roles and contributions"
        ]
        11 => array:2 [
          "identificador" => "sec0080"
          "titulo" => "Conflict of interest"
        ]
        12 => array:2 [
          "identificador" => "xack406795"
          "titulo" => "Acknowledgments"
        ]
        13 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2017-12-22"
    "fechaAceptado" => "2018-08-27"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1109938"
          "palabras" => array:6 [
            0 => "Colombia"
            1 => "Efficacy"
            2 => "Janus kinase"
            3 => "Rheumatoid arthritis"
            4 => "Safety"
            5 => "Tofacitinib"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1109939"
          "palabras" => array:6 [
            0 => "Colombia"
            1 => "Eficacia"
            2 => "Janus kinasa"
            3 => "Artritis reumatoide"
            4 => "Seguridad"
            5 => "Tofacitinib"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis &#40;RA&#41;&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objective</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">To conduct a post hoc analysis of tofacitinib efficacy and safety in Colombian patients enrolled in global phase III studies&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Data were pooled from Colombian patients with RA across four phase III tofacitinib studies&#58; ORAL Sync&#44; ORAL Scan&#44; ORAL Solo&#44; and ORAL Start&#46; Patients received tofacitinib 5 or 10<span class="elsevierStyleHsp" style=""></span>mg twice daily&#44; methotrexate &#40;ORAL Start only&#41;&#44; or placebo as single therapy &#40;ORAL Start and ORAL Solo&#41;&#44; or in combination with csDMARDs &#40;ORAL Sync and ORAL Scan&#41;&#46; Data were pooled from three studies with similar patient populations &#40;Sync&#44; Scan&#44; Solo&#41; for efficacy analyses&#44; and from all studies for safety analyses&#44; up to Month 24&#46; The efficacy analysis excluded ORAL Start due to the methotrexate-naive patient population&#44; and placebo and methotrexate groups&#44; due to low patient numbers&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Data pooled included 77 patients for efficacy&#44; and 125 for safety analyses&#46; Tofacitinib-treated patients showed improved American College of Rheumatology 20&#47;50&#47;70 response rates&#44; a mean Disease Activity Score 28-4 &#40;erythrocyte sedimentation rate&#41;&#44; and a mean change from baseline in Health Assessment Questionnaire-Disability Index&#46; Improvements were sustained in Months 12&#8211;24&#44; although patient numbers were low post-Month 12&#46; The most frequently reported adverse events were anemia&#44; headache&#44; influenza&#44; and increased blood creatine phosphokinase&#46; No tuberculosis cases&#44; serious adverse events&#44; or deaths were reported&#44; and few cases of herpes zoster or malignancies occurred&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusions</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Tofacitinib reduced RA signs and symptoms&#44; and improved physical function&#46; The efficacy and safety of tofacitinib in this Colombian sub-population were consistent with data from global phase III studies&#46;</p></span>"
        "secciones" => array:5 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Introduction"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Objective"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Methods"
          ]
          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Results"
          ]
          4 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Conclusions"
          ]
        ]
      ]
      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Introducci&#243;n</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Tofacitinib es un inhibidor oral de la janus kinasa para el tratamiento de la artritis reumatoide &#40;AR&#41;&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Objetivo</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">An&#225;lisis post hoc para evaluar la eficacia y seguridad de tofacitinib en los pacientes colombianos que participaron en los estudios globales de fase III&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">M&#233;todos</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">La informaci&#243;n se obtuvo de los pacientes colombianos con AR que participaron en 4 de los estudios de tofacitinib de fase III&#58; ORAL Sync&#44; ORAL Scan&#44; ORAL Solo y ORAL Start&#46; Los pacientes recibieron tofacitinib 5 o 10<span class="elsevierStyleHsp" style=""></span>mg 2 veces al d&#237;a&#44; ya sea en monoterapia &#40;ORAL Start y ORAL Solo&#41; o en combinaci&#243;n con csDMARDs &#40;ORAL Scan y ORAL Sync&#41;&#44; metotrexate &#40;ORAL Start&#41; o placebo&#46; Para el an&#225;lisis de eficacia se utilizaron 3 estudios que incluyeron poblaciones similares &#40;Sync&#44; Scan y Solo&#41; y para el an&#225;lisis de seguridad se utilizaron todos los estudios&#44; hasta el mes 24&#46; El an&#225;lisis de eficacia excluy&#243; tanto el estudio ORAL Start debido a poblaci&#243;n metotrexate naive como a los grupos placebo o metotrexate debido al bajo n&#250;mero de pacientes&#46;</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Se incluyeron 77 pacientes para el an&#225;lisis de eficacia y 125 para seguridad&#46; Los pacientes tratados con tofacitinib mostraron mejor&#237;as en las tasas de respuestas del American College of Rheumatology &#40;ACR&#41; 20&#47;50&#47;70&#44; en el promedio del Disease Activity Score &#40;DAS&#41; 28-4 &#40;velocidad de sedimentaci&#243;n globular&#41; y en el cambio promedio desde la basal en el Health Assessment Questionnaire-Disability Index &#40;HAQ-DI&#41;&#46; Las mejor&#237;as fueron sostenidas desde el mes 12 al mes 24&#44; aunque el n&#250;mero de pacientes luego del mes 12 fue bajo&#46; Los eventos adversos m&#225;s frecuentemente reportados fueron anemia&#44; cefalea&#44; influenza e incremento de la creatin-fosfoquinasa s&#233;rica&#46; No se reportaron casos de tuberculosis&#44; eventos adversos serios o muertes&#46; Ocurrieron casos poco frecuentes de herpes zoster y malignidades&#46;</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclusiones</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Tofacitinib redujo los signos y s&#237;ntomas de la AR y mejor&#243; la funci&#243;n f&#237;sica&#46; La eficacia y seguridad en esta subpoblaci&#243;n colombiana fue consistente con los resultados de los pacientes que participaron en los estudios globales de fase III&#46;</p></span>"
        "secciones" => array:5 [
          0 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "Introducci&#243;n"
          ]
          1 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Objetivo"
          ]
          2 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "M&#233;todos"
          ]
          3 => array:2 [
            "identificador" => "abst0045"
            "titulo" => "Resultados"
          ]
          4 => array:2 [
            "identificador" => "abst0050"
            "titulo" => "Conclusiones"
          ]
        ]
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:3 [
        "etiqueta" => "1"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0035">Indicated affiliation at the time&#44; the work was conducted&#46;</p>"
        "identificador" => "fn0005"
      ]
    ]
    "apendice" => array:1 [
      0 => array:1 [
        "seccion" => array:1 [
          0 => array:4 [
            "apendice" => "<p id="par0180" class="elsevierStylePara elsevierViewall"><elsevierMultimedia ident="upi0005"></elsevierMultimedia></p>"
            "etiqueta" => "Appendix A"
            "titulo" => "Supplementary data"
            "identificador" => "sec0090"
          ]
        ]
      ]
    ]
    "multimedia" => array:7 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Fig&#46; 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 3855
            "Ancho" => 2470
            "Tamanyo" => 332115
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Proportion of responders for &#40;A&#41; ACR20&#44; &#40;B&#41; ACR50 and &#40;C&#41; ACR70 &#40;SE&#41; over time for the tofacitinib 5 and 10<span class="elsevierStyleHsp" style=""></span>mg BID groups in the efficacy subpopulation &#40;FAS&#44; observed&#41;&#46;</p> <p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">ACR20&#47;50&#47;70&#58; American College of Rheumatology 20&#47;50&#47;70 response rates&#59; BID&#58; twice daily&#59; FAS&#58; full analysis set&#59; SE&#44; standard error&#46;</p> <p id="spar0065" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">N</span> represents the numbers of patients with non-missing ACR response&#46; Efficacy analyses were based on three studies&#58; ORAL Scan&#44; ORAL Solo and ORAL Sync&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Fig&#46; 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 1365
            "Ancho" => 2493
            "Tamanyo" => 121279
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Mean &#40;SE&#41; DAS28-4&#40;ESR&#41; over time for the tofacitinib 5 and 10<span class="elsevierStyleHsp" style=""></span>mg BID groups in the efficacy subpopulation &#40;FAS&#44; observed&#41;&#46;</p> <p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">BID&#58; twice daily&#59; DAS28-4&#40;ESR&#41;&#58; Disease Activity Score-erythrocyte sedimentation rate&#59; FAS&#58; full analysis set&#59; SE&#58; standard error&#46;</p> <p id="spar0080" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">N</span> represents the numbers of patients with non-missing DAS28-4&#40;ESR&#41;&#46; Efficacy analyses were based on three studies&#58; ORAL Scan&#44; ORAL Solo and ORAL Sync&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "fig0015"
        "etiqueta" => "Fig&#46; 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr3.jpeg"
            "Alto" => 1371
            "Ancho" => 2496
            "Tamanyo" => 134477
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Mean &#40;SE&#41; change from baseline in HAQ-DI &#40;SE&#41; over time for the tofacitinib 5 and 10<span class="elsevierStyleHsp" style=""></span>mg BID groups in the efficacy subpopulation &#40;FAS&#44; observed&#41;&#46;</p> <p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">BID&#58; twice daily&#59; FAS&#58; full analysis set&#59; HAQ-DI&#58; Health Assessment Questionnaire-Disability Index&#59; SE&#58; standard error&#46;</p> <p id="spar0095" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">N</span> represents the numbers of patients with non-missing HAQ-DI&#46; Efficacy analyses were based on three studies&#58; ORAL Scan&#44; ORAL Solo and ORAL Sync&#46;</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at1"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0105" class="elsevierStyleSimplePara elsevierViewall">BID&#58; twice daily&#59; BMI&#58; body mass index&#59; DAS28-4&#40;ESR&#41;&#58; Disease Activity Score28-4&#40;erythrocyte sedimentation rate&#41;&#59; HAQ-DI&#58; Health Assessment Questionnaire-Disability Index&#59; Other&#58; Black&#47;Asian&#47;Hispanic&#59; MTX&#58; methotrexate&#59; RA&#58; rheumatoid arthritis&#59; SD&#58; standard deviation&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Efficacy analyses population<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a></th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="4" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Safety analyses population<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a></th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Tofacitinib5<span class="elsevierStyleHsp" style=""></span>mg BID&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>33&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Tofacitinib10<span class="elsevierStyleHsp" style=""></span>mg BID&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>32&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Tofacitinib5<span class="elsevierStyleHsp" style=""></span>mg BID&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>53&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Tofacitinib10<span class="elsevierStyleHsp" style=""></span>mg BID&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>51&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Placebo&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>12&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">MTX&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Mean age&#44; years &#40;range&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">51&#46;5 &#40;31&#8211;74&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">51&#46;6 &#40;29&#8211;74&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">51&#46;0 &#40;26&#8211;74&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50&#46;9 &#40;21&#8211;74&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">52&#46;4 &#40;32&#8211;74&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">45&#46;8 &#40;20&#8211;67&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Female&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28 &#40;84&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30 &#40;93&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">45 &#40;84&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">46 &#40;90&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11 &#40;91&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8 &#40;88&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="7" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="7" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Race&#44; n &#40;&#37;&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>White&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;3&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;2&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Other&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">33 &#40;100&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31 &#40;96&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">53 &#40;100&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50 &#40;98&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12 &#40;100&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;100&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Mean RA duration&#44; years &#40;range&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#46;5 &#40;0&#46;2&#8211;25&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#46;1 &#40;0&#46;9&#8211;35&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#46;5 &#40;0&#46;1&#8211;25&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#46;2 &#40;0&#46;1&#8211;35&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&#46;0 &#40;0&#46;9&#8211;40&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;6 &#40;0&#46;1&#8211;14&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Mean BMI&#44; kg&#47;m</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">2</span></span><span class="elsevierStyleItalic">&#40;range&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">26&#46;6 &#40;18&#46;0&#8211;37&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&#46;6 &#40;14&#46;4&#8211;37&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&#46;8 &#40;18&#8211;37&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&#46;7 &#40;14&#46;4&#8211;37&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24&#46;5 &#40;14&#46;6&#8211;37&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23&#46;2 &#40;16&#46;9&#8211;32&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Baseline DAS28-4&#40;ESR&#41;&#44; mean &#40;SD&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#46;3 &#40;0&#46;79&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#46;2 &#40;1&#46;09&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#46;5 &#40;1&#46;00&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#46;4 &#40;1&#46;16&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#46;7 &#40;0&#46;71&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#46;1 &#40;0&#46;96&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Baseline HAQ-DI&#44; mean &#40;SD&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;6 &#40;0&#46;76&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;8 &#40;0&#46;66&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;7 &#40;0&#46;78&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;7 &#40;0&#46;63&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;6 &#40;0&#46;73&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;9 &#40;0&#46;64&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="7" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="7" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Previous RA treatment&#44; n &#40;&#37;&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Methotrexate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32 &#40;97&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32 &#40;100&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">32 &#40;60&#46;4&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32 &#40;62&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11 &#40;91&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Anti-malarial&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;9&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 &#40;12&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">7 &#40;13&#46;2&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;17&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;22&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Leflunomide&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;6&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">2 &#40;3&#46;8&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;16&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Sulfasalazine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;6&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;3&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;8&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2031598.png"
              ]
            ]
          ]
          "notaPie" => array:2 [
            0 => array:3 [
              "identificador" => "tblfn0005"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Efficacy analyses were based on three studies&#58; ORAL Scan&#44; ORAL Solo and ORAL Sync&#46;</p>"
            ]
            1 => array:3 [
              "identificador" => "tblfn0010"
              "etiqueta" => "b"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Safety analyses were based on four studies&#58; ORAL Scan&#44; ORAL Solo&#44; ORAL Sync and ORAL Start&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">Patient demographics and baseline characteristics by treatment sequence for patients included in the efficacy and safety analyses&#46;</p>"
        ]
      ]
      4 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at2"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0115" class="elsevierStyleSimplePara elsevierViewall">AE&#58; adverse event&#59; BID&#58; twice daily&#59; MTX&#58; methotrexate&#59; NA&#58; not applicable&#59; SAE&#44; serious adverse event&#59; TEAE&#58; treatment-emergent adverse event&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Tofacitinib 5<span class="elsevierStyleHsp" style=""></span>mg BID&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Tofacitinib 10<span class="elsevierStyleHsp" style=""></span>mg BID&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Placebo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">MTX&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>53&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>51&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>12&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Discontinuations</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Related to study drug</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>AE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;1&#46;9&#41;<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;2&#46;0&#41;<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Lack of efficacy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;11&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Not related to study drug&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 &#40;7&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;17&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;16&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;22&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">AEs</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">TEAE Month 0&#8211;3</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21 &#40;39&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18 &#40;35&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;58&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">TEAE Month 3&#8211;6</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19 &#40;34&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21 &#40;36&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;25&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">TEAE Month 6&#43;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">34 &#40;77&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">34 &#40;77&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 &#40;66&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">SAEs</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Deaths</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2031597.png"
              ]
            ]
          ]
          "notaPie" => array:2 [
            0 => array:3 [
              "identificador" => "tblfn0015"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Patient discontinued due to increased blood creatine phosphokinase&#44; but not adjudicated SAE</p>"
            ]
            1 => array:3 [
              "identificador" => "tblfn0020"
              "etiqueta" => "b"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Patient discontinued due a persistent elevation in function liver tests &#40;alkaline phosphatase&#44; alanine aminotransferase&#44; aspartate aminotransferase&#44; gamma-glutamyltransferase&#41;&#44; but not adjudicated SAE</p> <p class="elsevierStyleNotepara" id="npar0025">Placebo patients advanced to tofacitinib 5 or 10<span class="elsevierStyleHsp" style=""></span>mg BID at Month 3 or 6&#44; depending on American College of Rheumatology 20 response rate&#46;</p> <p class="elsevierStyleNotepara" id="npar0030">Safety analyses were based on data from four studies&#58; ORAL Scan&#44; ORAL Solo&#44; ORAL Sync and ORAL Start&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0110" class="elsevierStyleSimplePara elsevierViewall">Summary of safety outcomes for all treatment groups&#46;</p>"
        ]
      ]
      5 => array:8 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at3"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0135" class="elsevierStyleSimplePara elsevierViewall">BID&#58; twice daily&#59; MTX&#58; methotrexate&#59; NA&#58; not applicable&#59; TEAE&#58; treatment-emergent adverse event&#46;</p><p id="spar0140" class="elsevierStyleSimplePara elsevierViewall">Placebo patients could advance to tofacitinib 5 or 10<span class="elsevierStyleHsp" style=""></span>mg BID at Month 3 depending on American College of Rheumatology 20 response rate&#59; all remaining placebo patients advanced at Month 6 to tofacitinib 5 or 10<span class="elsevierStyleHsp" style=""></span>mg BID&#46; Abdominal pain upper was not listed for Month 0&#8211;3&#46;</p><p id="spar0145" class="elsevierStyleSimplePara elsevierViewall">Safety analyses were based on data from four studies&#58; ORAL Scan&#44; ORAL Solo&#44; ORAL Sync and ORAL Start&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="4" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Months 0&#8211;3</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="4" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Months 3&#8211;6</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="3" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Month 6&#43;</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Tofacitinib 5<span class="elsevierStyleHsp" style=""></span>mg BID&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Tofacitinib 10<span class="elsevierStyleHsp" style=""></span>mg BID&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Placebo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">MTX&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Tofacitinib 5<span class="elsevierStyleHsp" style=""></span>mg BID&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Tofacitinib 10<span class="elsevierStyleHsp" style=""></span>mg BID&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Placebo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">MTX&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Tofacitinib 5<span class="elsevierStyleHsp" style=""></span>mg BID&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Tofacitinib 10<span class="elsevierStyleHsp" style=""></span>mg BID&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">MTX&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>53&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>51&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>12&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>55&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>57&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>44&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>44&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;9&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;5&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;25&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;3&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;8&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 &#40;13&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;11&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;11&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diarrhea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;8&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 &#40;9&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 &#40;9&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Abdominal pain &#40;upper&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;1&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;25&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;6&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;11&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dyspepsia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;3&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;1&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;6&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Bronchitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;1&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;2&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;1&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;2&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;6&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Urinary tract infection&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;5&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;5&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;4&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;11&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;11&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Influenza&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;1&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;1&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;11&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;15&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;11&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Blood creatine phosphokinase increased&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;5&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;3&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;5&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;3&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 &#40;13&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;6&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hypercholesterolemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;2&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;1&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;2&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;6&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hypertriglyceridemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;1&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;2&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;1&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 &#40;9&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 &#40;9&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Headache&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;1&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;2&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;8&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;5&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;3&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;25&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 &#40;9&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;15&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hematuria&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;3&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;5&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 &#40;9&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;2&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Onychomycosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;8&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;2&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;2&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Erythema&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;8&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Skin lesion&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;8&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;2&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2031599.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0130" class="elsevierStyleSimplePara elsevierViewall">Most frequently reported TEAEs &#40;&#8805;5&#37;&#41; in any treatment group&#46;</p>"
        ]
      ]
      6 => array:5 [
        "identificador" => "upi0005"
        "tipo" => "MULTIMEDIAECOMPONENTE"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "Ecomponente" => array:2 [
          "fichero" => "mmc1.docx"
          "ficheroTamanyo" => 49180
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:54 [
            0 => array:3 [
              "identificador" => "bib0275"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Current therapies in rheumatoid arthritis&#58; a Latin American perspective"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "R&#46; Burgos-Vargas"
                            1 => "L&#46;J&#46; Catoggio"
                            2 => "C&#46; Galarza-Maldonado"
                            3 => "K&#46; Ostojich"
                            4 => "M&#46;H&#46; Cardiel"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.reuma.2012.09.001"
                      "Revista" => array:6 [
                        "tituloSerie" => "Reumatol Clin"
                        "fecha" => "2013"
                        "volumen" => "9"
                        "paginaInicial" => "106"
                        "paginaFinal" => "112"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23337169"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0280"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The epidemiology of rheumatoid arthritis in a cohort of Colombian patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "J&#46;E&#46; Machado-Alba"
                            1 => "A&#46;F&#46; Ruiz"
                            2 => "D&#46;A&#46; Medina Morales"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Rev Colomb Reumatol"
                        "fecha" => "2015"
                        "volumen" => "22"
                        "paginaInicial" => "148"
                        "paginaFinal" => "152"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0285"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Rheumatoid arthritis in African Colombians from Quibdo"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "J&#46;M&#46; Anaya"
                            1 => "P&#46;A&#46; Correa"
                            2 => "R&#46;D&#46; Mantilla"
                            3 => "F&#46; Jimenez"
                            4 => "T&#46; Kuffner"
                            5 => "J&#46;M&#46; McNicholl"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Semin Arthritis Rheum"
                        "fecha" => "2001"
                        "volumen" => "31"
                        "paginaInicial" => "191"
                        "paginaFinal" => "198"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11740799"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0290"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prevalencia de artritis reumatoide en Colombia&#58; una aproximaci&#243;n basada en la carga de la enfermedad durante el a&#241;o 2005"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "J&#46;A&#46; D&#237;az-Rojas"
                            1 => "F&#46;A&#46; D&#225;vila-Ram&#237;rez"
                            2 => "G&#46; Quintana-L&#243;pez"
                            3 => "F&#46; Aristiz&#225;bal-Guti&#233;rrez"
                            4 => "P&#46; Brown"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Rev Colomb Reumatol"
                        "fecha" => "2016"
                        "volumen" => "23"
                        "paginaInicial" => "11"
                        "paginaFinal" => "16"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0295"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs&#58; 2016 update"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;S&#46; Smolen"
                            1 => "R&#46; Landew&#233;"
                            2 => "J&#46; Bijlsma"
                            3 => "G&#46; Burmester"
                            4 => "K&#46; Chatzidionysiou"
                            5 => "M&#46; Dougados"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/annrheumdis-2016-210715"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Rheum Dis"
                        "fecha" => "2017"
                        "volumen" => "76"
                        "paginaInicial" => "960"
                        "paginaFinal" => "977"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28264816"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0300"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;A&#46; Singh"
                            1 => "K&#46;G&#46; Saag"
                            2 => "S&#46;L&#46; Bridges Jr&#46;"
                            3 => "E&#46;A&#46; Akl"
                            4 => "R&#46;R&#46; Bannuru"
                            5 => "M&#46;C&#46; Sullivan"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/art.39977"
                      "Revista" => array:6 [
                        "tituloSerie" => "Arthritis Rheumatol"
                        "fecha" => "2016"
                        "volumen" => "68"
                        "paginaInicial" => "1"
                        "paginaFinal" => "26"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27870508"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0305"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "First Latin American position paper on the pharmacological treatment of rheumatoid arthritis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "M&#46;H&#46; Cardiel"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Rheumatology &#40;Oxford&#41;"
                        "fecha" => "2006"
                        "volumen" => "45"
                        "numero" => "Suppl 2"
                        "paginaInicial" => "ii7"
                        "paginaFinal" => "ii22"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0310"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Treating rheumatoid arthritis in Latin America&#58; current challenges and future treatment strategies"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "M&#46;H&#46; Cardiel"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Int J Clin Rheumatol"
                        "fecha" => "2012"
                        "volumen" => "7"
                        "paginaInicial" => "139"
                        "paginaFinal" => "142"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0315"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Treatment of early rheumatoid arthritis in a multinational inception cohort of Latin American patients&#58; the GLADAR experience"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46;H&#46; Cardiel"
                            1 => "B&#46;A&#46; Pons-Estel"
                            2 => "M&#46;P&#46; Sacnun"
                            3 => "D&#46; Wojdyla"
                            4 => "V&#46; Saurit"
                            5 => "J&#46;C&#46; Marcos"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/RHU.0b013e31826d6610"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Rheumatol"
                        "fecha" => "2012"
                        "volumen" => "18"
                        "paginaInicial" => "327"
                        "paginaFinal" => "335"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23047532"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0320"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Challenges in the management of rheumatoid arthritis in developing countries"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "G&#46;M&#46; Mody"
                            1 => "M&#46;H&#46; Cardiel"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.berh.2008.04.003"
                      "Revista" => array:6 [
                        "tituloSerie" => "Best Pract Res Clin Rheumatol"
                        "fecha" => "2008"
                        "volumen" => "22"
                        "paginaInicial" => "621"
                        "paginaFinal" => "641"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18783741"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0325"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Long-term impact of early treatment on radiographic progression in rheumatoid arthritis&#58; a meta-analysis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "A&#46; Finckh"
                            1 => "M&#46;H&#46; Liang"
                            2 => "C&#46;M&#46; van Herckenrode"
                            3 => "P&#46;P&#46; de"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/art.22353"
                      "Revista" => array:6 [
                        "tituloSerie" => "Arthritis Rheum"
                        "fecha" => "2006"
                        "volumen" => "55"
                        "paginaInicial" => "864"
                        "paginaFinal" => "872"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17139662"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0330"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Tratamiento de la artritis reumatoide en Colombia&#46; Applicaci&#243;n pr&#225;ctica de los conceptos te&#243;ricos por parte de los reumat&#243;logos colombianos"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "C&#46;V&#46; Caballero Uribe"
                            1 => "J&#46;D&#46; Londo&#241;o"
                            2 => "J&#46;P&#46; Chalem"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Rev Colomb Reumatol"
                        "fecha" => "2002"
                        "volumen" => "9"
                        "paginaInicial" => "242"
                        "paginaFinal" => "250"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0335"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Epidemiological profile of Colombian patients with rheumatoid arthritis in a specialized care clinic"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "W&#46; Bautista-Molano"
                            1 => "D&#46; Fernandez-Avila"
                            2 => "R&#46; Jimenez"
                            3 => "R&#46; Cardozo"
                            4 => "A&#46; Marin"
                            5 => "M&#46;D&#46; Soler"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.reuma.2015.11.009"
                      "Revista" => array:6 [
                        "tituloSerie" => "Reumatol Clin"
                        "fecha" => "2016"
                        "volumen" => "12"
                        "paginaInicial" => "313"
                        "paginaFinal" => "318"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26708736"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0340"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Recomendaciones del comit&#233; de expertos de la Asociaci&#243;n Colombiana de Rheumatolog&#237;a para el empleo de terapia bloqueadora del factor de necrosis tumoral en artritis reumatoide"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;D&#46; Londo&#241;o"
                            1 => "J&#46;R&#46; Guti&#233;rrez"
                            2 => "M&#46;D&#46; Cort&#233;s"
                            3 => "O&#46;U&#46; Uribe"
                            4 => "H&#46; Gonz&#225;lez Buritica"
                            5 => "C&#46;V&#46; Caballero Uribe"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Rev Colomb Reumatol"
                        "fecha" => "2001"
                        "volumen" => "8"
                        "paginaInicial" => "296"
                        "paginaFinal" => "302"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0345"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effectiveness of treatment with biologic- and disease-modifying antirheumatic drugs in rheumatoid arthritis patients in Colombia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "J&#46;E&#46; Machado-Alba"
                            1 => "A&#46;F&#46; Ruiz"
                            2 => "M&#46;E&#46; Machado-Duque"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/ijcp.12809"
                      "Revista" => array:6 [
                        "tituloSerie" => "Int J Clin Pract"
                        "fecha" => "2016"
                        "volumen" => "70"
                        "paginaInicial" => "506"
                        "paginaFinal" => "511"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27238964"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0350"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Gu&#237;a de Pr&#225;ctica Cl&#237;nica artritis reumatoide"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "Universidad Nacional de Colombia"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Libro" => array:1 [
                        "fecha" => "2014"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0355"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Global Tuberculosis Report"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "World Health Organization"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Libro" => array:1 [
                        "fecha" => "2016"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0360"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Efficacy and safety of 40 mg adalimumab twice per month in Colombian patients with rheumatoid arthritis &#40;RA&#41; with failure of conventional treatment&#46; An open study in a group of unselected patients &#8220;Real life study&#8221;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46; Londono"
                            1 => "J&#46; Molina"
                            2 => "R&#46; Guzman"
                            3 => "C&#46; Caballero"
                            4 => "M&#46; Chalem"
                            5 => "M&#46; Janiot"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Ann Rheum Dis"
                        "fecha" => "2005"
                        "volumen" => "64"
                        "numero" => "Suppl&#46; III"
                        "paginaInicial" => "475"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0365"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cambio en la capacidad funcional&#44; calidad de vida y actividad de la enfermedad&#44; en un grupo de pacientes colombianos con artritis reumatoide refractaria al tratamiento convencional&#44; que recibieron terapia con Infliximab como medicamento de rescate"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "P&#46;J&#46; Londo&#241;o"
                            1 => "A&#46; Fernandez"
                            2 => "G&#46; Daniel"
                            3 => "J&#46;C&#46; Salazar"
                            4 => "D&#46;L&#46; Saiibi"
                            5 => "J&#46;F&#46; Molina"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Rev Med"
                        "fecha" => "2009"
                        "volumen" => "17"
                        "paginaInicial" => "40"
                        "paginaFinal" => "49"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0370"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical disease activity and acute phase reactant levels are discordant among patients with active rheumatoid arthritis&#58; acute phase reactant levels contribute separately to predicting outcome at one year"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46; Kay"
                            1 => "O&#46; Morgacheva"
                            2 => "S&#46;P&#46; Messing"
                            3 => "J&#46;M&#46; Kremer"
                            4 => "J&#46;D&#46; Greenberg"
                            5 => "G&#46;W&#46; Reed"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/ar4469"
                      "Revista" => array:5 [
                        "tituloSerie" => "Arthritis Res Ther"
                        "fecha" => "2014"
                        "volumen" => "16"
                        "paginaInicial" => "R40"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24485007"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0375"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Measures of rheumatoid arthritis disease activity&#58; patient &#40;PtGA&#41; and Provider &#40;PrGA&#41; Global Assessment of Disease Activity&#44; Disease Activity Score &#40;DAS&#41; and Disease Activity Score with 28-Joint Counts &#40;DAS28&#41;&#44; Simplified Disease Activity Index &#40;SDAI&#41;&#44; Clinical Disease Activity Index &#40;CDAI&#41;&#44; Patient Activity Score &#40;PAS&#41; and Patient Activity Score-II &#40;PASII&#41;&#44; Routine Assessment of Patient Index Data &#40;RAPID&#41;&#44; Rheumatoid Arthritis Disease Activity Index &#40;RADAI&#41; and Rheumatoid Arthritis Disease Activity Index-5 &#40;RADAI-5&#41;&#44; Chronic Arthritis Systemic Index &#40;CASI&#41;&#44; Patient-Based Disease Activity Score With ESR &#40;PDAS1&#41; and Patient-Based Disease Activity Score without ESR &#40;PDAS2&#41;&#44; and Mean Overall Index for Rheumatoid Arthritis &#40;MOI-RA&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "J&#46;K&#46; Anderson"
                            1 => "L&#46; Zimmerman"
                            2 => "L&#46; Caplan"
                            3 => "K&#46; Michaud"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Arthritis Care Res &#40;Hoboken&#41;"
                        "fecha" => "2011"
                        "volumen" => "63"
                        "numero" => "Suppl 11"
                        "paginaInicial" => "S14"
                        "paginaFinal" => "S36"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0380"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Correlation between rapid-3&#44; DAS28&#44; CDAI and SDAI as a measure of disease activity in a cohort of Colombian patients with rheumatoid arthritis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;G&#46;B&#46; Munoz"
                            1 => "R&#46;B&#46; Giraldo"
                            2 => "A&#46;M&#46; Santos"
                            3 => "J&#46;M&#46; Bello-Gualteros"
                            4 => "J&#46;C&#46; Rueda"
                            5 => "E&#46;L&#46; Saldarriaga"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s10067-016-3521-5"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Rheumatol"
                        "fecha" => "2017"
                        "volumen" => "36"
                        "paginaInicial" => "1143"
                        "paginaFinal" => "1148"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28013433"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0385"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Phase IIb dose-ranging study of the oral JAK inhibitor tofacitinib &#40;CP-690&#44;550&#41; or adalimumab monotherapy versus placebo in patients with active rheumatoid arthritis with an inadequate response to disease-modifying antirheumatic drugs"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46; Fleischmann"
                            1 => "M&#46; Cutolo"
                            2 => "M&#46;C&#46; Genovese"
                            3 => "E&#46;B&#46; Lee"
                            4 => "K&#46;S&#46; Kanik"
                            5 => "S&#46; Sadis"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/art.33383"
                      "Revista" => array:6 [
                        "tituloSerie" => "Arthritis Rheum"
                        "fecha" => "2012"
                        "volumen" => "64"
                        "paginaInicial" => "617"
                        "paginaFinal" => "629"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21952978"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0390"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A phase IIb dose-ranging study of the oral JAK inhibitor tofacitinib &#40;CP-690&#44;550&#41; versus placebo in combination with background methotrexate in patients with active rheumatoid arthritis and an inadequate response to methotrexate alone"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;M&#46; Kremer"
                            1 => "S&#46; Cohen"
                            2 => "B&#46;E&#46; Wilkinson"
                            3 => "C&#46;A&#46; Connell"
                            4 => "J&#46;L&#46; French"
                            5 => "J&#46; Gomez-Reino"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/art.33419"
                      "Revista" => array:6 [
                        "tituloSerie" => "Arthritis Rheum"
                        "fecha" => "2012"
                        "volumen" => "64"
                        "paginaInicial" => "970"
                        "paginaFinal" => "981"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22006202"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib0395"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The safety and efficacy of a JAK inhibitor in patients with active rheumatoid arthritis&#58; results of a double-blind&#44; placebo-controlled phase IIa trial of three dosage levels of CP-690&#44;550 versus placebo"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;M&#46; Kremer"
                            1 => "B&#46;J&#46; Bloom"
                            2 => "F&#46;C&#46; Breedveld"
                            3 => "J&#46;H&#46; Coombs"
                            4 => "M&#46;P&#46; Fletcher"
                            5 => "D&#46; Gruben"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/art.24567"
                      "Revista" => array:6 [
                        "tituloSerie" => "Arthritis Rheum"
                        "fecha" => "2009"
                        "volumen" => "60"
                        "paginaInicial" => "1895"
                        "paginaFinal" => "1905"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19565475"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib0400"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Open-label tofacitinib and double-blind atorvastatin in rheumatoid arthritis patients&#58; a randomised study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "I&#46;B&#46; McInnes"
                            1 => "H&#46;Y&#46; Kim"
                            2 => "S&#46;H&#46; Lee"
                            3 => "D&#46; Mandel"
                            4 => "Y&#46;W&#46; Song"
                            5 => "C&#46;A&#46; Connell"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/annrheumdis-2012-202442"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Rheum Dis"
                        "fecha" => "2014"
                        "volumen" => "73"
                        "paginaInicial" => "124"
                        "paginaFinal" => "131"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23482473"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0405"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Phase II study of tofacitinib &#40;CP-690&#44;550&#41; combined with methotrexate in patients with rheumatoid arthritis and an inadequate response to methotrexate"
                      "autores" => array:1 [
                        0 => array:3 [
                          "colaboracion" => "Tofacitinib Study Investigators"
                          "etal" => false
                          "autores" => array:5 [
                            0 => "Y&#46; Tanaka"
                            1 => "M&#46; Suzuki"
                            2 => "H&#46; Nakamura"
                            3 => "S&#46; Toyoizumi"
                            4 => "S&#46;H&#46; Zwillich"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Arthritis Care Res &#40;Hoboken&#41;"
                        "fecha" => "2011"
                        "volumen" => "63"
                        "paginaInicial" => "1150"
                        "paginaFinal" => "1158"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib0410"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Efficacy and safety of tofacitinib as monotherapy in Japanese patients with active rheumatoid arthritis&#58; a 12-week&#44; randomized&#44; phase 2 study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "Y&#46; Tanaka"
                            1 => "T&#46; Takeuchi"
                            2 => "H&#46; Yamanaka"
                            3 => "H&#46; Nakamura"
                            4 => "S&#46; Toyoizumi"
                            5 => "S&#46; Zwillich"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3109/14397595.2014.995875"
                      "Revista" => array:6 [
                        "tituloSerie" => "Mod Rheumatol"
                        "fecha" => "2015"
                        "volumen" => "25"
                        "paginaInicial" => "514"
                        "paginaFinal" => "521"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25496464"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib0415"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Placebo-controlled trial of tofacitinib monotherapy in rheumatoid arthritis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46; Fleischmann"
                            1 => "J&#46; Kremer"
                            2 => "J&#46; Cush"
                            3 => "H&#46; Schulze-Koops"
                            4 => "C&#46;A&#46; Connell"
                            5 => "J&#46;D&#46; Bradley"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa1109071"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2012"
                        "volumen" => "367"
                        "paginaInicial" => "495"
                        "paginaFinal" => "507"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22873530"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib0420"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Tofacitinib in combination with nonbiologic disease-modifying antirheumatic drugs in patients with active rheumatoid arthritis&#58; a randomized trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46; Kremer"
                            1 => "Z&#46;-G&#46; Li"
                            2 => "S&#46; Hall"
                            3 => "R&#46; Fleischmann"
                            4 => "M&#46; Genovese"
                            5 => "E&#46; Martin-Mola"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.7326/0003-4819-159-4-201308200-00006"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Intern Med"
                        "fecha" => "2013"
                        "volumen" => "159"
                        "paginaInicial" => "253"
                        "paginaFinal" => "261"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24026258"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib0425"
              "etiqueta" => "31"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Tofacitinib &#40;CP-690&#44;550&#41; in patients with rheumatoid arthritis receiving methotrexate&#58; twelve-month data from a twenty-four-month phase III randomized radiographic study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "D&#46; van der Heijde"
                            1 => "Y&#46; Tanaka"
                            2 => "R&#46; Fleischmann"
                            3 => "E&#46; Keystone"
                            4 => "J&#46; Kremer"
                            5 => "C&#46; Zerbini"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/art.37816"
                      "Revista" => array:6 [
                        "tituloSerie" => "Arthritis Rheum"
                        "fecha" => "2013"
                        "volumen" => "65"
                        "paginaInicial" => "559"
                        "paginaFinal" => "570"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23348607"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib0430"
              "etiqueta" => "32"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Tofacitinib or adalimumab versus placebo in rheumatoid arthritis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46;F&#46; van Vollenhoven"
                            1 => "R&#46; Fleischmann"
                            2 => "S&#46; Cohen"
                            3 => "E&#46;B&#46; Lee"
                            4 => "J&#46;A&#46; Garc&#237;a Meijide"
                            5 => "S&#46; Wagner"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa1112072"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2012"
                        "volumen" => "367"
                        "paginaInicial" => "508"
                        "paginaFinal" => "519"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22873531"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            32 => array:3 [
              "identificador" => "bib0435"
              "etiqueta" => "33"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Tofacitinib versus methotrexate in rheumatoid arthritis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "E&#46;B&#46; Lee"
                            1 => "R&#46; Fleischmann"
                            2 => "S&#46; Hall"
                            3 => "B&#46; Wilkinson"
                            4 => "J&#46; Bradley"
                            5 => "D&#46; Gruben"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa1310476"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2014"
                        "volumen" => "370"
                        "paginaInicial" => "2377"
                        "paginaFinal" => "2386"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24941177"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            33 => array:3 [
              "identificador" => "bib0440"
              "etiqueta" => "34"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Tofacitinib &#40;CP-690&#44;550&#41; in combination with methotrexate in patients with active rheumatoid arthritis with an inadequate response to tumour necrosis factor inhibitors&#58; a randomised phase 3 trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "G&#46;R&#46; Burmester"
                            1 => "R&#46; Blanco"
                            2 => "C&#46; Charles-Schoeman"
                            3 => "J&#46; Wollenhaupt"
                            4 => "C&#46; Zerbini"
                            5 => "B&#46; Benda"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(12)61424-X"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "2013"
                        "volumen" => "381"
                        "paginaInicial" => "451"
                        "paginaFinal" => "460"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23294500"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            34 => array:3 [
              "identificador" => "bib0445"
              "etiqueta" => "35"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Safety and efficacy of tofacitinib&#44; an oral Janus kinase inhibitor&#44; for the treatment of rheumatoid arthritis in open-label&#44; longterm extension studies"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46; Wollenhaupt"
                            1 => "J&#46; Silverfield"
                            2 => "E&#46;B&#46; Lee"
                            3 => "J&#46;R&#46; Curtis"
                            4 => "S&#46;P&#46; Wood"
                            5 => "K&#46; Soma"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3899/jrheum.130683"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Rheumatol"
                        "fecha" => "2014"
                        "volumen" => "41"
                        "paginaInicial" => "837"
                        "paginaFinal" => "852"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24692527"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            35 => array:3 [
              "identificador" => "bib0450"
              "etiqueta" => "36"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Tofacitinib&#44; an oral Janus kinase inhibitor&#44; as monotherapy or with background methotrexate&#44; in Japanese patients with rheumatoid arthritis&#58; an open-label&#44; long-term extension study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "H&#46; Yamanaka"
                            1 => "Y&#46; Tanaka"
                            2 => "T&#46; Takeuchi"
                            3 => "N&#46; Sugiyama"
                            4 => "H&#46; Yuasa"
                            5 => "S&#46; Toyoizumi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/s13075-016-0932-2"
                      "Revista" => array:5 [
                        "tituloSerie" => "Arthritis Res Ther"
                        "fecha" => "2016"
                        "volumen" => "18"
                        "paginaInicial" => "34"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26818974"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            36 => array:3 [
              "identificador" => "bib0455"
              "etiqueta" => "37"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Tofacitinib&#44; an oral Janus kinase inhibitor&#44; in the treatment of rheumatoid arthritis&#58; safety and efficacy in open-label&#44; long-term extension studies over 9 years"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46; Wollenhaupt"
                            1 => "J&#46; Silverfield"
                            2 => "E&#46;B&#46; Lee"
                            3 => "K&#46; Terry"
                            4 => "K&#46; Kwok"
                            5 => "S&#46; Strengholt"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/art.39972"
                      "Revista" => array:6 [
                        "tituloSerie" => "Arthritis Rheumatol"
                        "fecha" => "2017"
                        "volumen" => "69"
                        "paginaInicial" => "683"
                        "paginaFinal" => "684"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27788282"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            37 => array:3 [
              "identificador" => "bib0460"
              "etiqueta" => "38"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Tofacitinib&#44; an oral Janus kinase inhibitor&#44; for the treatment of Latin American patients with rheumatoid arthritis&#58; pooled efficacy and safety analyses of Phase 3 and long-term extension studies"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46;C&#46; Radominski"
                            1 => "M&#46;H&#46; Cardiel"
                            2 => "G&#46; Citera"
                            3 => "A&#46; Goecke"
                            4 => "J&#46;J&#46; Jaller"
                            5 => "A&#46;B&#46; Lomonte"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:2 [
                        "tituloSerie" => "Reumatol Clin"
                        "fecha" => "2016"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            38 => array:3 [
              "identificador" => "bib0465"
              "etiqueta" => "39"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Safety of tofacitinib in the treatment of rheumatoid arthritis in Latin America compared with the rest of the world population"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "O&#46;M&#46; Casta&#241;eda"
                            1 => "F&#46;J&#46; Romero"
                            2 => "A&#46; Salinas"
                            3 => "G&#46; Citera"
                            4 => "E&#46; Mysler"
                            5 => "O&#46; Rillo"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/RHU.0000000000000498"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Rheumatol"
                        "fecha" => "2017"
                        "volumen" => "23"
                        "paginaInicial" => "193"
                        "paginaFinal" => "199"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28145906"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            39 => array:3 [
              "identificador" => "bib0470"
              "etiqueta" => "40"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "F&#46;C&#46; Arnett"
                            1 => "S&#46;M&#46; Edworthy"
                            2 => "D&#46;A&#46; Bloch"
                            3 => "D&#46;J&#46; McShane"
                            4 => "J&#46;F&#46; Fries"
                            5 => "N&#46;S&#46; Cooper"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Arthritis Rheum"
                        "fecha" => "1988"
                        "volumen" => "31"
                        "paginaInicial" => "315"
                        "paginaFinal" => "324"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3358796"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            40 => array:3 [
              "identificador" => "bib0475"
              "etiqueta" => "41"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "2012 Brazilian Society of Rheumatology Consensus for the treatment of rheumatoid arthritis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "L&#46;M&#46; da Mota"
                            1 => "B&#46;A&#46; Cruz"
                            2 => "C&#46;V&#46; Brenol"
                            3 => "I&#46;A&#46; Pereira"
                            4 => "L&#46;S&#46; Rezende-Fronza"
                            5 => "M&#46;B&#46; Bertolo"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Rev Bras Reumatol"
                        "fecha" => "2012"
                        "volumen" => "52"
                        "paginaInicial" => "152"
                        "paginaFinal" => "174"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22460407"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            41 => array:3 [
              "identificador" => "bib0480"
              "etiqueta" => "42"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Update of the Mexican College of Rheumatology guidelines for the pharmacologic treatment of rheumatoid arthritis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46;H&#46; Cardiel"
                            1 => "A&#46; Diaz-Borjon"
                            2 => "E&#46;M&#46; Vazquez Del Mercado"
                            3 => "J&#46;I&#46; Gamez-Nava"
                            4 => "L&#46;A&#46; Barile Fabris"
                            5 => "T&#46;C&#46; Pacheco"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Reumatol Clin"
                        "fecha" => "2014"
                        "volumen" => "10"
                        "paginaInicial" => "227"
                        "paginaFinal" => "240"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            42 => array:3 [
              "identificador" => "bib0485"
              "etiqueta" => "43"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "XELJANZ&#174; &#40;tofacitinib&#41; highlights of prescribing information"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "US Food and Drug Administration"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Libro" => array:1 [
                        "fecha" => "2017"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            43 => array:3 [
              "identificador" => "bib0490"
              "etiqueta" => "44"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Tuberculosis and other opportunistic infections in tofacitinib-treated patients with rheumatoid arthritis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "K&#46;L&#46; Winthrop"
                            1 => "S&#46;H&#46; Park"
                            2 => "A&#46; Gul"
                            3 => "M&#46;H&#46; Cardiel"
                            4 => "J&#46;J&#46; Gomez-Reino"
                            5 => "Y&#46; Tanaka"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/annrheumdis-2015-207319"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Rheum Dis"
                        "fecha" => "2016"
                        "volumen" => "75"
                        "paginaInicial" => "1133"
                        "paginaFinal" => "1138"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26318385"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            44 => array:3 [
              "identificador" => "bib0495"
              "etiqueta" => "45"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effectiveness of recommendations to prevent reactivation of latent tuberculosis infection in patients treated with tumor necrosis factor antagonists"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "L&#46; Carmona"
                            1 => "J&#46;J&#46; G&#243;mez-Reino"
                            2 => "V&#46; Rodr&#237;guez-Valverde"
                            3 => "D&#46; Montero"
                            4 => "E&#46; Pascual-G&#243;mez"
                            5 => "E&#46;M&#46; Mola"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/art.21043"
                      "Revista" => array:6 [
                        "tituloSerie" => "Arthritis Rheum"
                        "fecha" => "2005"
                        "volumen" => "52"
                        "paginaInicial" => "1766"
                        "paginaFinal" => "1772"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15934089"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            45 => array:3 [
              "identificador" => "bib0500"
              "etiqueta" => "46"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Differences in reactivation of tuberculosis induced from anti-TNF treatments are based on bioavailability in granulomatous tissue"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46; Marino"
                            1 => "D&#46; Sud"
                            2 => "H&#46; Plessner"
                            3 => "P&#46;L&#46; Lin"
                            4 => "J&#46; Chan"
                            5 => "J&#46;L&#46; Flynn"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1371/journal.pcbi.0030194"
                      "Revista" => array:6 [
                        "tituloSerie" => "PLoS Comput Biol"
                        "fecha" => "2007"
                        "volumen" => "3"
                        "paginaInicial" => "1909"
                        "paginaFinal" => "1924"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17953477"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            46 => array:3 [
              "identificador" => "bib0505"
              "etiqueta" => "47"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Safety of synthetic and biological DMARDs&#58; a systematic literature review informing the 2013 update of the EULAR recommendations for management of rheumatoid arthritis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46; Ramiro"
                            1 => "C&#46; Gaujoux-Viala"
                            2 => "J&#46;L&#46; Nam"
                            3 => "J&#46;S&#46; Smolen"
                            4 => "M&#46; Buch"
                            5 => "L&#46; Gossec"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/annrheumdis-2013-204575"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Rheum Dis"
                        "fecha" => "2014"
                        "volumen" => "73"
                        "paginaInicial" => "529"
                        "paginaFinal" => "535"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24401994"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            47 => array:3 [
              "identificador" => "bib0510"
              "etiqueta" => "48"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Tofacitinib for Treatment of Rheumatoid Arthritis &#40;NDA 203214&#41; Advisory Committee Meeting Briefing Document &#40;NDA 203214&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "FDA"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Libro" => array:1 [
                        "fecha" => "2012"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            48 => array:3 [
              "identificador" => "bib0515"
              "etiqueta" => "49"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Brazilian biologic registry&#58; biobadaBrasil implementation process and preliminary results"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "D&#46;C&#46; Titton"
                            1 => "I&#46;G&#46; Silveira"
                            2 => "P&#46; Louzada-Junior"
                            3 => "A&#46;L&#46; Hayata"
                            4 => "H&#46;M&#46; Carvalho"
                            5 => "R&#46; Ranza"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Rev Bras Reumatol"
                        "fecha" => "2011"
                        "volumen" => "51"
                        "paginaInicial" => "152"
                        "paginaFinal" => "160"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21584421"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            49 => array:3 [
              "identificador" => "bib0520"
              "etiqueta" => "50"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Patient survival and safety with biologic therapy&#46; Results of the Mexican National Registry Biobadamex 1&#46;0"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "L&#46; Ventura-Rios"
                            1 => "D&#46; Banuelos-Ramirez"
                            2 => "M&#46;C&#46; Hernandez-Quiroz"
                            3 => "R&#46;M&#46; Robles-San"
                            4 => "F&#46; Irazoque-Palazuelos"
                            5 => "M&#46;V&#46; Goycochea-Robles"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.reuma.2012.02.010"
                      "Revista" => array:6 [
                        "tituloSerie" => "Reumatol Clin"
                        "fecha" => "2012"
                        "volumen" => "8"
                        "paginaInicial" => "189"
                        "paginaFinal" => "194"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22673388"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            50 => array:3 [
              "identificador" => "bib0525"
              "etiqueta" => "51"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Tofacitinib&#44; an oral Janus kinase inhibitor&#44; in the treatment of rheumatoid arthritis&#58; open-label&#44; long-term extension safety and efficacy up to 6 years"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46; Wollenhaupt"
                            1 => "J&#46; Silverfield"
                            2 => "E&#46;B&#46; Lee"
                            3 => "S&#46;P&#46; Wood"
                            4 => "K&#46; Terry"
                            5 => "H&#46; Nakamura"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "Arthritis Rheumatol"
                        "fecha" => "2014"
                        "volumen" => "74"
                        "paginaInicial" => "S375"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            51 => array:3 [
              "identificador" => "bib0530"
              "etiqueta" => "52"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Epidemiology in Latin America and the Caribbean&#58; current situation and challenges"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46;M&#46; Barreto"
                            1 => "J&#46;J&#46; Miranda"
                            2 => "J&#46;P&#46; Figueroa"
                            3 => "M&#46;I&#46; Schmidt"
                            4 => "S&#46; Munoz"
                            5 => "P&#46;P&#46; Kuri-Morales"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/ije/dys017"
                      "Revista" => array:6 [
                        "tituloSerie" => "Int J Epidemiol"
                        "fecha" => "2012"
                        "volumen" => "41"
                        "paginaInicial" => "557"
                        "paginaFinal" => "571"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22407860"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            52 => array:3 [
              "identificador" => "bib0535"
              "etiqueta" => "53"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The neglected tropical diseases of Latin America and the Caribbean&#58; a review of disease burden and distribution and a roadmap for control and elimination"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "P&#46;J&#46; Hotez"
                            1 => "M&#46;E&#46; Bottazzi"
                            2 => "C&#46; Franco-Paredes"
                            3 => "S&#46;K&#46; Ault"
                            4 => "M&#46;R&#46; Periago"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1371/journal.pntd.0000300"
                      "Revista" => array:5 [
                        "tituloSerie" => "PLoS Negl Trop Dis"
                        "fecha" => "2008"
                        "volumen" => "2"
                        "paginaInicial" => "e300"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18820747"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            53 => array:3 [
              "identificador" => "bib0540"
              "etiqueta" => "54"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Velez P&#44; Jaller JJ&#44; Otero W&#44; Persand K&#44; Mahgoub EY&#44; Mebus C&#44; et al&#46; Tofacitinib&#44; an oral Janus kinase inhibitor&#44; in patients from Latin America with rheumatoid arthritis&#58; pooled efficacy and safety analyses&#46; Asociaci&#243;n Colombiana de Rheumatolog&#237;a&#44; Medell&#237;n&#44; Colombia&#44; August 15&#8211;18&#44; 2013&#46;"
                ]
              ]
            ]
          ]
        ]
      ]
    ]
    "agradecimientos" => array:1 [
      0 => array:4 [
        "identificador" => "xack406795"
        "titulo" => "Acknowledgments"
        "texto" => "<p id="par0170" class="elsevierStylePara elsevierViewall">The authors would like to thank the patients&#44; investigators and study teams involved in the studies included in this analysis&#46; The authors would also like to thank Elaine Hoffman for providing statistical support&#46; Medical writing support&#44; under the direction of the authors&#44; was provided by Rebecca Douglas&#44; PhD&#44; CMC Connect&#44; a division of Complete Medical Communications Ltd&#44; Macclesfield&#44; UK and was funded by Pfizer Inc&#44; New York&#44; NY&#44; USA in accordance with Good Publication Practice &#40;GPP3&#41; guidelines &#40;Ann Intern Med 2015&#59;163&#58;461&#8211;464&#41;&#46; This analysis was previously presented in poster form at Asociaci&#243;n Colombiana de Reumatolog&#237;a Medell&#237;n&#44; Colombia&#44; August 15&#8211;18&#44; 2013&#46;<a class="elsevierStyleCrossRef" href="#bib0540"><span class="elsevierStyleSup">54</span></a></p>"
        "vista" => "all"
      ]
    ]
  ]
  "idiomaDefecto" => "en"
  "url" => "/24444405/0000002500000004/v1_201905160826/S2444440519300329/v1_201905160826/en/main.assets"
  "Apartado" => array:4 [
    "identificador" => "53648"
    "tipo" => "SECCION"
    "en" => array:2 [
      "titulo" => "Original Investigation"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "en"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/24444405/0000002500000004/v1_201905160826/S2444440519300329/v1_201905160826/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2444440519300329?idApp=UINPBA00004N"
]

Article information

ISSN: 24444405
Original language: English

DOI:10.1016/j.rcreue.2018.08.002

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 November	1	0	1
2024 October	48	11	59
2024 September	51	5	56
2024 August	45	4	49
2024 July	35	4	39
2024 June	40	3	43
2024 May	34	2	36
2024 April	31	5	36
2024 March	46	7	53
2024 February	53	2	55
2024 January	28	1	29
2023 December	47	3	50
2023 November	17	1	18
2023 October	19	2	21
2023 September	11	3	14
2023 August	11	3	14
2023 July	16	2	18
2023 June	22	3	25
2023 May	41	5	46
2023 April	64	6	70
2023 March	46	2	48
2023 February	25	4	29
2023 January	23	11	34
2022 December	13	3	16
2022 November	36	8	44
2022 October	32	8	40
2022 September	15	7	22
2022 August	21	10	31
2022 July	20	6	26
2022 June	27	7	34
2022 May	26	8	34
2022 April	31	10	41
2022 March	17	10	27
2022 February	25	3	28
2022 January	14	3	17
2021 December	13	9	22
2021 November	15	8	23
2021 October	48	9	57
2021 September	29	13	42
2021 August	37	13	50
2021 July	24	11	35
2021 June	28	8	36
2021 May	28	8	36
2021 April	81	34	115
2021 March	55	8	63
2021 February	27	7	34
2021 January	29	14	43
2020 December	28	3	31
2020 November	17	4	21
2020 October	14	3	17
2020 September	21	6	27
2020 August	29	8	37
2020 July	13	8	21
2020 June	22	11	33
2020 May	17	4	21
2020 April	16	2	18
2020 March	12	0	12
2020 February	18	5	23
2020 January	9	2	11
2019 December	17	3	20
2019 November	9	3	12
2019 October	12	7	19
2019 September	12	2	14
2019 August	8	4	12
2019 July	13	17	30
2019 June	20	14	34
2019 May	12	5	17

Show all

Indexed in:

Follow us:

Statistics

Indexed in:

Follow us:

Statistics

Subscribe to our newsletter