Combination of granulocyte–monocyte apheresis and tofacitinib: Multicentre and retrospective study | Gastroenterología y Hepatología (English Edition)

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"identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:10 [ 0 => array:3 [ "entidad" => "Gastroenterology Department, Hospital Universitario de Galdakao, Biobizkaia Health Research Institute, Galdakao, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Gastroenterology Department, Hospital Universitari Germans Trias i Pujol, Badalona, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Gastroenterology Department, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Gastroenterology Department, Hospital Universitari Vall d’Hebron, Barcelona, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Gastroenterology 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author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Combinación de aféresis de granulocitos-monocitos y tofacitinib: estudio multicéntrico y retrospectivo" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1184 "Ancho" => 1550 "Tamanyo" => 63568 ] ] "descripcion" => array:1 [ "en" => "Clinical disease activity at baseline, 1 month, and 6 months (n=12) after granulocyte and monocyte apheresis. The partial Mayo score significantly decreased 1 and 6 months after the last apheresis session. Results are expressed as mean±SD." ] ] ] "textoCompleto" => "IntroductionGranulocyte–monocyte apheresis (GMA) can selectively deplete activated neutrophils/monocytes/macrophages by adsorption and has been associated with significant clinical efficacy in patients with inflammatory bowel disease (IBD).<a class="elsevierStyleCrossRefs" href="#bib0145">1,2</a> The mechanism of action of GMA relies on the interaction between cellular and humoral blood components and cellulose acetate beads immersed in physiological saline solution.<a class="elsevierStyleCrossRef" href="#bib0155">3</a> After passing through the device, the blood is further reinfused to the patient.<a class="elsevierStyleCrossRefs" href="#bib0160">4–7</a>Several studies have shown the efficacy and safety of tofacitinib (TOFA), an oral, small-molecule Janus kinase inhibitor in the treatment of moderate to severe ulcerative colitis (UC) patients who failed to achieve clinical remission, did not respond to conventional treatments, or lost response to tumor necrosis factor (TNF)-α antagonists.<a class="elsevierStyleCrossRefs" href="#bib0180">8,9</a> However, despite the efficacy of small-molecules in UC, a significant proportion of patients receiving TOFA do not respond or lose response over time.<a class="elsevierStyleCrossRef" href="#bib0180">8</a> In contrast, the concomitant use of GMA plus TOFA has been described with up to 71% of patients achieving clinical remission at 10 weeks in seven patients with refractory UC.<a class="elsevierStyleCrossRef" href="#bib0190">10</a> Different studies and case series have also shown promising results when combining GMA with different biologics, as well as with vedolizumab or ustekinumab.<a class="elsevierStyleCrossRefs" href="#bib0165">5,7,16,11–13</a>The aim of our study was to evaluate the efficacy and safety of combining GMA and TOFA after primary non-response (PNR) or loss of response (LOR) to this drug in patients with refractory UC.Patients and methodsStudy populationA retrospective, multicentre study was performed in 7 IBD Units in Spain. We included all patients with refractory UC who received the combination of GMA and TOFA between September 2019 and October 2022.Treatment and assessmentsWe collected data on age at diagnosis, disease location according to Montreal classification,<a class="elsevierStyleCrossRef" href="#bib0210">14</a> previous UC-related medications, concomitant medical therapy, past relevant disease history, smoking habits, body mass index, disease duration, and extraintestinal manifestations. All IBD Units involved in this study follow the current clinical practices guidelines from the European Crohn's and Colitis Organisation (ECCO)<a class="elsevierStyleCrossRef" href="#bib0215">15</a> and the Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU).<a class="elsevierStyleCrossRef" href="#bib0220">16</a>The number of GMA sessions, its frequency, the filtered blood volume and the length of each session were compiled, along with the clinical data described above. The mean volume per session was calculated by dividing the sum of the total blood volume filtered in all these sessions by the number of sessions. Efficacy was assessed 1 and 6 months after finishing GMA by partial Mayo score, including also C-reactive protein (CRP) and fecal calprotectin (FC) at the same time points. The proportion of patients with FC values<250mg/kg was calculated. Data regarding the need of TOFA dose escalation, use of new immunomodulators or biologics and colectomy were also registered during follow-up.The decision to start GMA combination therapy and its regimen were made on a case-by case basis at each hospital based on the individual characteristics of the patient and the clinical situation, as the use of GMA plus TOFA is not an established treatment for UC. All patients were treated with the same GMA device (Adacolumn®, JIMRO, Takasaki, Japan) receiving weekly, twice-weekly or three times per week sessions through a peripheral venous access. The filtered volume and the duration of the sessions were chosen at the physician's discretion (the recommended volume is 1800mL per session of 60min, though this schedule can be adjusted according to the clinical and individual characteristics of each patient).<a class="elsevierStyleCrossRef" href="#bib0155">3</a> An intravenous bolus of weight-based low molecular-weight heparin was administered to all patients before starting GMA.All adverse events (AEs) occurring during follow-up were recorded, and serious AEs were defined as any AE leading to treatment discontinuation, hospitalization, disability, colectomy, or death.DefinitionsThe definition of PNR included the persistence of symptoms with a partial or complete absence of improvement in the partial Mayo score during the first 8–16 weeks of TOFA therapy. Secondary LOR was defined as a clinical relapse with a partial Mayo score≥2 and a bleeding subscore>1 after 16 weeks of starting TOFA and after a period of clinical remission achieved during the induction period. Clinical remission was defined as a partial Mayo score≤2 with no individual subscore>1 and a rectal bleeding score of 0.Statistical analysisDescriptive statistics of the sample were examined, using frequencies and percentages for categorical variables and means and SD for continuous variables. Variables with biased distributions were expressed as median and interquartile ranges (IQRs). The Wilcoxon test was used to assess differences in continuous variables between the different time points. Statistical significance was defined as p<.05.ResultsA total of twelve patients were treated with this combination therapy. Patient characteristics are summarized in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. The median age at the moment of starting GMA was 46 years (IQR, 37–58) and 67% of patients were women, with 75% being non-smokers. UC was classified as extensive (E3) in eight cases (67%) and left-sided in four (33%). The median disease duration was 27 months (IQR, 11–112). No patient reported extraintestinal manifestations.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Patients were receiving TOFA 10mg bid (75%), 5mg bid (17%), or 15mg bid (8%), and 33% also received systemic steroids at baseline. TOFA was maintained at stable doses while combined with GMA. All patients had prior exposure to anti-TNF agents, 67% to infliximab and 58% to adalimumab. Median partial Mayo score at baseline was 7 (IQR, 5–7). Median CRP at baseline was 11mg/L (IQR, 5–30; N=8) and FC 1013mg/kg (IQR, 757–2047; N=8).The characteristics of GMA therapy are summarized in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>. GMA was started mostly after PNR (73%), and the median number of GMA sessions was 17 (IQR, 11–27). Sessions were twice-weekly in most patients (58%), with 17% undergoing three-weekly or weekly sessions. The treatment protocols consisted in filtering 1800–2700mL per session with a 30–50mL/min rate for 45–90min. In most of the patients, the filtered volume was 1800mL with sessions of 45–70min. Half of the patients received maintenance therapy with GMA. The median clinical follow-up was 11 months (IQR, 6–20).<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>Clinical outcomesFollow-up data at 1 month was available for all patients and for 9 patients (75%) after 6 months. Partial Mayo score significantly decreased to a median of 2 (IQR, 0–3; p=0.027) 1 month after the last GMA session, and to a median of 0 (IQR, 0–3; p=0.062) at 6 months (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a> and <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>). Clinical remission was achieved by 6 patients after 1 (50%) and 6 months (67%). CF values<250mg/kg were obtained by 2 and 4 patients at 1 and 6 months (data available in 5 and 7 patients, respectively). There were no statistically significant changes in CRP or FC levels after 1 (p=0.39 and 0.23, respectively) or 6 months (p=0.11 and 0.08, respectively).<elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia>No patients receiving TOFA 5mg bid (n=2) required dose escalation and one patient under 10mg bid was able to de-escalate to 5mg bid. All patients under steroids at baseline were able to stop them. During follow-up, one patient required a new course of steroids. Four patients (36%) stopped TOFA and started a new therapy (ustekinumab [75%] and upadacitinib [25%]) and no patient required colectomy. No patients reported AEs related to this combination therapy.DiscussionHere we report the feasibility of combining GMA with TOFA after PNR or LOR to this agent in a cohort of patients with multi-refractory UC. All of these patients had prior exposure to anti-TNF agents, mainly infliximab and adalimumab, and one third were receiving steroids at baseline. GMA was mostly started after PNR, and our data show how this strategy could potentially reduce the inflammatory burden and even avoid switching to another therapy in a cohort of patients with limited therapeutic options.In recent years, anti-TNF, anti-interleukin and anti-integrin monoclonal antibodies have demonstrated their ability to achieve high rates of remission in the management of UC. Unfortunately, in a significant number of patients subsequent lines of therapy are required due to an inadequate response or a relapse after an initial response.<a class="elsevierStyleCrossRef" href="#bib0225">17</a> Among the most recent therapeutic options, TOFA has also shown its efficacy in UC patients who do not respond or lose response to TNF-α antagonists achieving clinical remission rates of 18.5% and 16.6% after 8 weeks in the Oral Clinical Trials for Tofacitinib in Ulcerative Colitis (OCTAVE) induction 1 and 2 trials, respectively.<a class="elsevierStyleCrossRef" href="#bib0180">8</a>In addition to its use in other inflammatory conditions as rheumatoid arthritis, ocular Behçet's disease, systemic lupus erythematosus or pustular psoriasis, GMA is approved in Europe for inducing remission in patients with active UC and Crohn's disease.<a class="elsevierStyleCrossRef" href="#bib0230">18</a> The usual GMA protocol generally consists in 1–2 sessions per week usually up to a total of 10 sessions,<a class="elsevierStyleCrossRef" href="#bib0195">11</a> with a length of 60–90min per session.<a class="elsevierStyleCrossRefs" href="#bib0160">4–7,19</a> Intensive GMA of bi-weekly sessions has been shown to be superior to weekly GMA in patients with refractory UC, both in terms of remission rate and time to remission.<a class="elsevierStyleCrossRefs" href="#bib0240">20,21</a> In our study, almost 60% of the patients received twice-weekly GMA sessions, with a median number of 10 sessions and a median duration of 82min per session. In addition, half of the patients received maintenance GMA, reflecting the use of more intensive therapy in this highly refractory subset of patients. However, maintenance GMA still remains controversial.<a class="elsevierStyleCrossRef" href="#bib0195">11</a>GMA has shown long-term benefit in patients with active UC and insufficient response or intolerance to immunosuppressants or biologics, a difficult-to-treat patient subgroup.<a class="elsevierStyleCrossRef" href="#bib0250">22</a> Its unique mechanism of action provides immunological effects that are expected to act synergistically when combined with more conventional agents for UC. There are several studies and case series already showing promising results when combining GMA with different biologics like anti-TNF agents, as well as with vedolizumab or ustekinumab.<a class="elsevierStyleCrossRefs" href="#bib0165">5,7,11–13</a> Most of the evidence with this combination therapy has been described with biologics, and its use with small molecules is still very limited.<a class="elsevierStyleCrossRef" href="#bib0190">10</a> In our cohort, partial Mayo score significantly decreased 1 and 6 months after the last GMA session, although we did not observe significant changes in biomarkers. Notably, no patient required colectomy during follow-up; all patients under steroids at baseline were able to stop them and only one patient required a new course of steroids. This is in line with previous studies that have demonstrated the steroid-sparing effect of adsorptive GMA.<a class="elsevierStyleCrossRef" href="#bib0255">23</a> Thus, increasing evidence supports that GMA might be an attractive alternative in the setting of steroid-dependency even in patients receiving biologics and small molecules.<a class="elsevierStyleCrossRef" href="#bib0195">11</a>Only one previous case series has described the feasibility of combining GMA with TOFA during the induction in patients with refractory UC.<a class="elsevierStyleCrossRef" href="#bib0190">10</a> In seven patients who received twice-weekly concomitant sessions of GMA plus TOFA during the induction period, 71.4% achieved clinical remission at 10 weeks. The percentages of patients with mucosal healing and complete mucosal healing at 10 weeks were 100% and 43%, respectively. There were statistically significant changes in the full Mayo score and endoscopic subscore at 10 weeks compared to baseline. Here, Tanida et al. concluded that combining intensive GMA plus TOFA was well tolerated and may be useful for inducing clinical remission in patients with refractory UC.<a class="elsevierStyleCrossRef" href="#bib0190">10</a> It should be noted that, in our study, the strategy consisted in combining GMA with TOFA after PNR or LOR to this agent and not during the induction. Moreover, it could be expected that a more intensive GMA regimen might have improved the results observed in our cohort. Despite these considerations, both reports highlight the safety of this combination therapy and the possibility of improving outcomes in different scenarios of patients treated with small molecules.GMA selectively depletes activated leukocytes of the myeloid lineage, mainly by removing neutrophils, the most prominent cellular population during disease flares.<a class="elsevierStyleCrossRef" href="#bib0195">11</a> Besides, it has several secondary immunomodulatory effects, including release of anti-inflammatory mediators, decreased production of proinflammatory cytokines, reduced neutrophil chemotaxis and endothelial cell adhesion, down-regulation of circulating leukocyte cell surface proteins, and induction of regulatory T and B-cells (Tregs and Bregs).<a class="elsevierStyleCrossRefs" href="#bib0195">11,24</a> Furthermore, in the event of secondary LOR to anti-TNFs, recent evidence suggests that GMA may contribute to re-establishing a treatment effect in a proportion of patients,<a class="elsevierStyleCrossRefs" href="#bib0195">11,25</a> probably by reducing anti-drug antibodies and without an influence on trough levels.<a class="elsevierStyleCrossRefs" href="#bib0205">13,26</a> The exact mechanism of action of the combination of GMA with TOFA is still unknown and should be further explored.GMA is safe and well tolerated in the treatment of IBD in steroid-dependent cases and also in combination with biologics.<a class="elsevierStyleCrossRefs" href="#bib0195">11,27,28</a> In our population, no patient reported any AE related to the combination therapy. The low rate of surgery and the ability to reduce steroids with few AEs may allow to control the disease and the inflammatory process without switching the therapy in refractory patients with limited treatment options once they have already used TOFA. Our results regarding the safety profile appear to be even better than the ones described by Tanida et al., where three patients showed an AE mainly attributed to TOFA (an orolabial herpes and temporary increase in creatinine phosphokinase and triglyceride).<a class="elsevierStyleCrossRef" href="#bib0190">10</a>Our study has also some limitations that should be addressed. The retrospective design and the variability of TOFA and GMA regimens may limit our ability to obtain more definite conclusions. Though, this study could serve as a basis for future clinical trials exploring the potential of combining GMA with TOFA in refractory UC patients with an inadequate response to this agent. Further large prospective studies are expected to clarify the exact mechanisms underlying the beneficial effect of this strategy and define the characteristics of patients with the highest probability of responding to this strategy.In conclusion, our results suggest the potential effectiveness, safety and tolerability of combining GMA with TOFA in selected UC patients with an insufficient or inadequate response to this drug. This approach could expand the number of therapeutic options available for some patients with refractory UC and deserves more research.Authors’ contributionsIR-L and JLC: study design, data analysis and drafting the manuscript.FC, EG, CH, EI, EL, YZ, MB-A, DG: data collection.DG and JLC: revised the manuscript for important intellectual content.Ethical considerationsInformed consent was obtained from all patients included in the study. The study was approved by the local Ethics Committee of the coordinating center (EPA2017050).FundingIR-L is funded by a research grant from Gobierno Vasco – Eusko Jaurlaritza [grant number 2020111061] and by a research grant from Biobizkaia Health Research Institute [Grant No BCB/I/LIB/22/008].Conflict of interestIR-L has received financial support for traveling and educational activities from or has served as an advisory board member for Abbvie, Adacyte, Celltrion, Chiesi, Danone, Ferring, Faes Farma, Janssen, Galapagos, MSD, Pfizer, Roche, Takeda, and Tillotts Pharma. Financial support for research: Tillotts Pharma.YZ has received support for conference attendance, speaker fees, research support and consulting fees from AbbVie, Adacyte, Almirall, Amgen, Dr. Falk Pharma, FAES Pharma, Ferring, Janssen, MSD, Otsuka, Pfizer, Shire, Takeda, Galapagos, Boehringer Ingelheim and Tillotts Pharma.MB-A has received financial support for traveling and educational activities from or has served as an advisory board member for Pfizer, MSD, Takeda, AbbVie, Kern, Janssen, Fresenius Kabi, Galapagos, Lilly, BMS, Faes Farma, Chiesi and Adacyte.JLC has received financial support for traveling and educational activities from or has served as an advisory board member for Abbvie, Adacyte, Chiesi, Ferring, Janssen, MSD, Pfizer, Takeda, and Tillotts Pharma.The remaining authors have no conflicts of interest to declare." "textoCompletoSecciones" => array:1 [ "secciones" => array:14 [ 0 => array:3 [ "identificador" => "xres2247316" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Patients and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1880100" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres2247315" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Pacientes y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1880099" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Patients and methods" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Study population" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Treatment and assessments" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Definitions" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Statistical analysis" ] ] ] 6 => array:3 [ "identificador" => "sec0035" "titulo" => "Results" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0040" "titulo" => "Clinical outcomes" ] ] ] 7 => array:2 [ "identificador" => "sec0045" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0050" "titulo" => "Authors’ contributions" ] 9 => array:2 [ "identificador" => "sec0055" "titulo" => "Ethical considerations" ] 10 => array:2 [ "identificador" => "sec0060" "titulo" => "Funding" ] 11 => array:2 [ "identificador" => "sec0065" "titulo" => "Conflict of interest" ] 12 => array:2 [ "identificador" => "xack775404" "titulo" => "Acknowledgements" ] 13 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2023-08-29" "fechaAceptado" => "2024-01-18" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1880100" "palabras" => array:4 [ 0 => "Tofacitinib" 1 => "Granulocyte–monocyte apheresis" 2 => "Inflammatory bowel disease" 3 => "Ulcerative colitis" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1880099" "palabras" => array:4 [ 0 => "Tofacitinib" 1 => "Aféresis de granulocitos-monocitos" 2 => "Enfermedad inflamatoria intestinal" 3 => "Colitis ulcerosa" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "ObjectiveGranulocyte–monocyte apheresis (GMA) has shown to be safe and effective in treating ulcerative colitis (UC), also in combination with biologics. The objective of this study is to evaluate the efficacy and safety of combining GMA after primary non-response (PNR) or loss of response (LOR) to tofacitinib (TOFA) in patients with UC. Patients and methodsRetrospective study including all patients with refractory UC who received GMA plus TOFA. Efficacy was assessed 1 and 6 months after finishing GMA by partial Mayo score, C-reactive protein (CRP) and fecal calprotectin (FC). Descriptive statistics and non-parametric tests were used in the statistical analysis. ResultsTwelve patients were included (median 46 years [IQR, 37–58]; 67% female; 67% E3). Patients were mostly receiving TOFA 10mg bid (75%), and 33% also concomitant steroids at baseline. Median partial Mayo score at baseline was 7 (IQR, 5–7), and it decreased to a median of 2 (IQR, 0–3) and 0 (IQR, 0–3) after 1 and 6 months (p=0.027 and 0.020, respectively), while no differences were found in CRP and FC. Clinical remission was achieved by 6 patients both at 1 (50%) and 6 months (67%). CF values<250mg/kg were achieved by 2 and 4 patients at 1 and 6 months (data available in 5 and 7 patients, respectively). No patient required dose-escalation of TOFA, and one patient was able to de-escalate the drug. No patient required colectomy and all patients under steroids were able to stop them. ConclusionThe combination of GMA and TOFA can be effective in selected cases of UC after PNR or LOR to this drug." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Patients and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "ObjetivoLa aféresis de granulocitos-monocitos (GMA) ha demostrado ser segura y eficaz en el tratamiento de la colitis ulcerosa (CU), incluso en combinación con fármacos biológicos. El objetivo de este estudio es evaluar la eficacia y la seguridad de combinar GMA con tofacitinib (TOFA) tras falta de respuesta primaria o pérdida de respuesta a este fármaco en pacientes con CU. Pacientes y métodosEstudio retrospectivo que incluyó a todos los pacientes con CU refractaria que recibieron GMA más TOFA. La eficacia se evaluó 1 y 6 meses después de finalizar la GMA mediante la puntuación de Mayo parcial, la proteína C reactiva (PCR) y la calprotectina fecal (CF). El análisis estadístico se realizó mediante parámetros descriptivos y pruebas no paramétricas. ResultadosSe incluyeron doce pacientes (mediana 46 años [RIQ, 37-58]; 67% mujeres; 67% E3). En el momento basal, la mayoría de los pacientes estaban recibiendo TOFA 10mg dos veces al día (75%), y el 33% también recibían esteroides concomitantes. La mediana de la puntuación de Mayo parcial basal fue de 7 (RIC, 5-7), y disminuyó a una mediana de 2 (RIC, 0-3) y 0 (RIC, 0-3) tras 1 y 6 meses (p=0,027 y 0,020, respectivamente), mientras que no se encontraron diferencias en la PCR y la CF. Se logró remisión clínica en 6 pacientes tanto al mes (50%) como a los 6 meses (67%). Dos y 4 pacientes alcanzaron valores de CF <250mg/kg el mes 1 y el 6 (datos disponibles en 5 y 7 pacientes, respectivamente). Ningún paciente requirió aumentar la dosis de TOFA y un paciente pudo reducirla. Ningún paciente necesitó colectomía y todos los pacientes tratados con esteroides pudieron suspenderlos. ConclusiónLa combinación de GMA y TOFA puede ser eficaz en casos seleccionados de CU tras la falta de respuesta primaria o pérdida de respuesta a este fármaco." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Pacientes y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1184 "Ancho" => 1550 "Tamanyo" => 63568 ] ] "descripcion" => array:1 [ "en" => "Clinical disease activity at baseline, 1 month, and 6 months (n=12) after granulocyte and monocyte apheresis. The partial Mayo score significantly decreased 1 and 6 months after the last apheresis session. Results are expressed as mean±SD." ] ] 1 => 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:1 [ "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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Variable \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">GMA plus tofacitinibN=12 \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="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Age (years)</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">Median [IQR] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 [37–58] \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="2" 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="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sex, 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">Women \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (67) \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="2" 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="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Smoking habit, 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">Never \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (75) \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">Former smoker \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (17) \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">Smoker \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" 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="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Disease location, 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">Left-sided colitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (33) \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">Extensive colitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (67) \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="2" 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="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Previous treatments, 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">Mesalazine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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) \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">Systemic steroids \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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) \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">Thiopurines \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (83) \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">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">2 (17) \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">Infliximab \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (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">Adalimumab \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (58) \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">Golimumab \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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></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">Ustekinumab \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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></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">Vedolizumab \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (42) \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="2" align="left" valign="\n \t\t\t\t\ttop\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">Concomitant steroids, 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">4 (33) \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="2" 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="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Dose of tofacitinib, 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">5mg bid \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (17) \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">10mg bid \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (75) \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">15mg bid \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" 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="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Partial Mayo score at baseline</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">Median [IQR] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 [5–7] \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="2" 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="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">C-reactive protein at baseline (mg/L)</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">Median [IQR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 [5–30] \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="2" 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="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Fecal calprotectin at baseline (mg/kg)</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">Median [IQR] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1013 [757–2047] \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3662769.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Patient characteristics." ] ] 2 => 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:1 [ "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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Characteristics \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">GMA plus tofacitinibN=12 \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="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Indication of apheresis, 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">Primary failure/partial response \t\t\t\t\t\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">8 (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">Secondary loss of response \t\t\t\t\t\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">4 (33) \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="2" 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="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Type of primary nonresponse, 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">Partial response \t\t\t\t\t\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 (88) \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">No response \t\t\t\t\t\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 (12) \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="2" 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="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Number of sessions at induction</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">Median [Q1, Q3] \t\t\t\t\t\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">10 [7.5–10] \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">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4–10 \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="2" 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="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Total number of sessions</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">Median [Q1, Q3] \t\t\t\t\t\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">17 [11–27] \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="2" 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="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Frequency of sessions, 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">Weekly \t\t\t\t\t\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 (17) \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">Twice-weekly \t\t\t\t\t\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">8 (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">Three times per week \t\t\t\t\t\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 (17) \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="2" 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="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Filtered volume, mL</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">Median [IQR] \t\t\t\t\t\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">1880 [1800–2265] \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">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1800–2700 \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="2" 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="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Duration of sessions, min</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">Median [IQR] \t\t\t\t\t\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">82min (63–90) \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">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">45–90 \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="2" align="left" valign="\n \t\t\t\t\ttop\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">Maintenance apheresis, 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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 (50) \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="2" 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="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Follow-up, months</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">Median [IQR] \t\t\t\t\t\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">11 [6–20] \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3662770.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Characteristics of the granulocyte and monocyte apheresis (GMA) treatment (n=12) and duration of follow-up." ] ] 3 => 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:1 [ "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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Clinical outcome \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">TofacitinibN=12 \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="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Response at 1 month, median [Q1, Q3]</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">Partial Mayo score \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 [0–4] \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">Fecal calprotectin, mg/kg \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">600 [140–800] \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="2" 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="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Response at 6 months, median [Q1, Q3]</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">Partial Mayo score \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 [0–3] \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">Fecal calprotectin, mg/kg \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">244 [85–510] \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="2" 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="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Physician Global Assessment</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">No activity \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \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">Mild \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \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">Moderate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \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">Severe \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \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="2" align="left" valign="\n \t\t\t\t\ttop\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">Tofacitinib de-escalation, 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">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">New biologic or small-molecule, 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">4 \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">Steroid withdrawal, 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">3 \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">New steroid course, 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">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">Surgery, 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">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3662771.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Clinical outcomes (n=12)." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:28 [ 0 => array:3 [ "identificador" => "bib0145" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Therapeutic leukocytapheresis for inflammatory bowel disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A.R. 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Original article

Combination of granulocyte–monocyte apheresis and tofacitinib: Multicentre and retrospective study

Combinación de aféresis de granulocitos-monocitos y tofacitinib: estudio multicéntrico y retrospectivo

Iago Rodríguez-Lagoa,

Corresponding author

iago.r.lago@gmail.com

Corresponding author.

, Fiorella Cañeteb,c, Elena Guerra-del-Ríod, Claudia Herrera-deGuisee, Eva Iglesiasf, Eduardo Leog, Yamile Zabanah, Manuel Barreiro-de Acostai, Daniel Ginardj, José Luis Cabriadaa

a Gastroenterology Department, Hospital Universitario de Galdakao, Biobizkaia Health Research Institute, Galdakao, Spain

b Gastroenterology Department, Hospital Universitari Germans Trias i Pujol, Badalona, Spain

c Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain

d Gastroenterology Department, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas, Spain

e Gastroenterology Department, Hospital Universitari Vall d’Hebron, Barcelona, Spain

f Gastroenterology Department, Hospital Universitario Reina Sofía, Córdoba, Spain

g Gastroenterology Department, Hospital Universitario Virgen del Rocío, Sevilla, Spain

h Gastroenterology Department, Hospital Universitari Mútua Terrassa, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Terrassa, Spain

i Gastroenterology Department, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain

j Gastroenterology Department, Hospital Universitario Son Espases, Palma, Spain

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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Clinical disease activity at baseline&#44; 1 month&#44; and 6 months &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>12&#41; after granulocyte and monocyte apheresis&#46; The partial Mayo score significantly decreased 1 and 6 months after the last apheresis session&#46; Results are expressed as mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Granulocyte&#8211;monocyte apheresis &#40;GMA&#41; can selectively deplete activated neutrophils&#47;monocytes&#47;macrophages by adsorption and has been associated with significant clinical efficacy in patients with inflammatory bowel disease &#40;IBD&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">1&#44;2</span></a> The mechanism of action of GMA relies on the interaction between cellular and humoral blood components and cellulose acetate beads immersed in physiological saline solution&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">3</span></a> After passing through the device&#44; the blood is further reinfused to the patient&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">4&#8211;7</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Several studies have shown the efficacy and safety of tofacitinib &#40;TOFA&#41;&#44; an oral&#44; small-molecule Janus kinase inhibitor in the treatment of moderate to severe ulcerative colitis &#40;UC&#41; patients who failed to achieve clinical remission&#44; did not respond to conventional treatments&#44; or lost response to tumor necrosis factor &#40;TNF&#41;-&#945; antagonists&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">8&#44;9</span></a> However&#44; despite the efficacy of small-molecules in UC&#44; a significant proportion of patients receiving TOFA do not respond or lose response over time&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">8</span></a> In contrast&#44; the concomitant use of GMA plus TOFA has been described with up to 71&#37; of patients achieving clinical remission at 10 weeks in seven patients with refractory UC&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">10</span></a> Different studies and case series have also shown promising results when combining GMA with different biologics&#44; as well as with vedolizumab or ustekinumab&#46;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">5&#44;7&#44;16&#44;11&#8211;13</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The aim of our study was to evaluate the efficacy and safety of combining GMA and TOFA after primary non-response &#40;PNR&#41; or loss of response &#40;LOR&#41; to this drug in patients with refractory UC&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Patients and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Study population</span><p id="par0020" class="elsevierStylePara elsevierViewall">A retrospective&#44; multicentre study was performed in 7 IBD Units in Spain&#46; We included all patients with refractory UC who received the combination of GMA and TOFA between September 2019 and October 2022&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Treatment and assessments</span><p id="par0025" class="elsevierStylePara elsevierViewall">We collected data on age at diagnosis&#44; disease location according to Montreal classification&#44;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">14</span></a> previous UC-related medications&#44; concomitant medical therapy&#44; past relevant disease history&#44; smoking habits&#44; body mass index&#44; disease duration&#44; and extraintestinal manifestations&#46; All IBD Units involved in this study follow the current clinical practices guidelines from the European Crohn&#39;s and Colitis Organisation &#40;ECCO&#41;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">15</span></a> and the Spanish Working Group on Crohn&#39;s Disease and Ulcerative Colitis &#40;GETECCU&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">16</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The number of GMA sessions&#44; its frequency&#44; the filtered blood volume and the length of each session were compiled&#44; along with the clinical data described above&#46; The mean volume per session was calculated by dividing the sum of the total blood volume filtered in all these sessions by the number of sessions&#46; Efficacy was assessed 1 and 6 months after finishing GMA by partial Mayo score&#44; including also C-reactive protein &#40;CRP&#41; and fecal calprotectin &#40;FC&#41; at the same time points&#46; The proportion of patients with FC values<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>250<span class="elsevierStyleHsp" style=""></span>mg&#47;kg was calculated&#46; Data regarding the need of TOFA dose escalation&#44; use of new immunomodulators or biologics and colectomy were also registered during follow-up&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">The decision to start GMA combination therapy and its regimen were made on a case-by case basis at each hospital based on the individual characteristics of the patient and the clinical situation&#44; as the use of GMA plus TOFA is not an established treatment for UC&#46; All patients were treated with the same GMA device &#40;Adacolumn&#174;&#44; JIMRO&#44; Takasaki&#44; Japan&#41; receiving weekly&#44; twice-weekly or three times per week sessions through a peripheral venous access&#46; The filtered volume and the duration of the sessions were chosen at the physician&#39;s discretion &#40;the recommended volume is 1800<span class="elsevierStyleHsp" style=""></span>mL per session of 60<span class="elsevierStyleHsp" style=""></span>min&#44; though this schedule can be adjusted according to the clinical and individual characteristics of each patient&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">3</span></a> An intravenous bolus of weight-based low molecular-weight heparin was administered to all patients before starting GMA&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">All adverse events &#40;AEs&#41; occurring during follow-up were recorded&#44; and serious AEs were defined as any AE leading to treatment discontinuation&#44; hospitalization&#44; disability&#44; colectomy&#44; or death&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Definitions</span><p id="par0045" class="elsevierStylePara elsevierViewall">The definition of PNR included the persistence of symptoms with a partial or complete absence of improvement in the partial Mayo score during the first 8&#8211;16 weeks of TOFA therapy&#46; Secondary LOR was defined as a clinical relapse with a partial Mayo score<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>2 and a bleeding subscore<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>1 after 16 weeks of starting TOFA and after a period of clinical remission achieved during the induction period&#46; Clinical remission was defined as a partial Mayo score<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>2 with no individual subscore<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>1 and a rectal bleeding score of 0&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Statistical analysis</span><p id="par0050" class="elsevierStylePara elsevierViewall">Descriptive statistics of the sample were examined&#44; using frequencies and percentages for categorical variables and means and SD for continuous variables&#46; Variables with biased distributions were expressed as median and interquartile ranges &#40;IQRs&#41;&#46; The Wilcoxon test was used to assess differences in continuous variables between the different time points&#46; Statistical significance was defined as <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;05&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Results</span><p id="par0055" class="elsevierStylePara elsevierViewall">A total of twelve patients were treated with this combination therapy&#46; Patient characteristics are summarized in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; The median age at the moment of starting GMA was 46 years &#40;IQR&#44; 37&#8211;58&#41; and 67&#37; of patients were women&#44; with 75&#37; being non-smokers&#46; UC was classified as extensive &#40;E3&#41; in eight cases &#40;67&#37;&#41; and left-sided in four &#40;33&#37;&#41;&#46; The median disease duration was 27 months &#40;IQR&#44; 11&#8211;112&#41;&#46; No patient reported extraintestinal manifestations&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">Patients were receiving TOFA 10<span class="elsevierStyleHsp" style=""></span>mg bid &#40;75&#37;&#41;&#44; 5<span class="elsevierStyleHsp" style=""></span>mg bid &#40;17&#37;&#41;&#44; or 15<span class="elsevierStyleHsp" style=""></span>mg bid &#40;8&#37;&#41;&#44; and 33&#37; also received systemic steroids at baseline&#46; TOFA was maintained at stable doses while combined with GMA&#46; All patients had prior exposure to anti-TNF agents&#44; 67&#37; to infliximab and 58&#37; to adalimumab&#46; Median partial Mayo score at baseline was 7 &#40;IQR&#44; 5&#8211;7&#41;&#46; Median CRP at baseline was 11<span class="elsevierStyleHsp" style=""></span>mg&#47;L &#40;IQR&#44; 5&#8211;30&#59; <span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>8&#41; and FC 1013<span class="elsevierStyleHsp" style=""></span>mg&#47;kg &#40;IQR&#44; 757&#8211;2047&#59; <span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>8&#41;&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">The characteristics of GMA therapy are summarized in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46; GMA was started mostly after PNR &#40;73&#37;&#41;&#44; and the median number of GMA sessions was 17 &#40;IQR&#44; 11&#8211;27&#41;&#46; Sessions were twice-weekly in most patients &#40;58&#37;&#41;&#44; with 17&#37; undergoing three-weekly or weekly sessions&#46; The treatment protocols consisted in filtering 1800&#8211;2700<span class="elsevierStyleHsp" style=""></span>mL per session with a 30&#8211;50<span class="elsevierStyleHsp" style=""></span>mL&#47;min rate for 45&#8211;90<span class="elsevierStyleHsp" style=""></span>min&#46; In most of the patients&#44; the filtered volume was 1800<span class="elsevierStyleHsp" style=""></span>mL with sessions of 45&#8211;70<span class="elsevierStyleHsp" style=""></span>min&#46; Half of the patients received maintenance therapy with GMA&#46; The median clinical follow-up was 11 months &#40;IQR&#44; 6&#8211;20&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Clinical outcomes</span><p id="par0070" class="elsevierStylePara elsevierViewall">Follow-up data at 1 month was available for all patients and for 9 patients &#40;75&#37;&#41; after 6 months&#46; Partial Mayo score significantly decreased to a median of 2 &#40;IQR&#44; 0&#8211;3&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;027&#41; 1 month after the last GMA session&#44; and to a median of 0 &#40;IQR&#44; 0&#8211;3&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;062&#41; at 6 months &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a> and <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; Clinical remission was achieved by 6 patients after 1 &#40;50&#37;&#41; and 6 months &#40;67&#37;&#41;&#46; CF values<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>250<span class="elsevierStyleHsp" style=""></span>mg&#47;kg were obtained by 2 and 4 patients at 1 and 6 months &#40;data available in 5 and 7 patients&#44; respectively&#41;&#46; There were no statistically significant changes in CRP or FC levels after 1 &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;39 and 0&#46;23&#44; respectively&#41; or 6 months &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;11 and 0&#46;08&#44; respectively&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">No patients receiving TOFA 5<span class="elsevierStyleHsp" style=""></span>mg bid &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#41; required dose escalation and one patient under 10<span class="elsevierStyleHsp" style=""></span>mg bid was able to de-escalate to 5<span class="elsevierStyleHsp" style=""></span>mg bid&#46; All patients under steroids at baseline were able to stop them&#46; During follow-up&#44; one patient required a new course of steroids&#46; Four patients &#40;36&#37;&#41; stopped TOFA and started a new therapy &#40;ustekinumab &#91;75&#37;&#93; and upadacitinib &#91;25&#37;&#93;&#41; and no patient required colectomy&#46; No patients reported AEs related to this combination therapy&#46;</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Discussion</span><p id="par0080" class="elsevierStylePara elsevierViewall">Here we report the feasibility of combining GMA with TOFA after PNR or LOR to this agent in a cohort of patients with multi-refractory UC&#46; All of these patients had prior exposure to anti-TNF agents&#44; mainly infliximab and adalimumab&#44; and one third were receiving steroids at baseline&#46; GMA was mostly started after PNR&#44; and our data show how this strategy could potentially reduce the inflammatory burden and even avoid switching to another therapy in a cohort of patients with limited therapeutic options&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">In recent years&#44; anti-TNF&#44; anti-interleukin and anti-integrin monoclonal antibodies have demonstrated their ability to achieve high rates of remission in the management of UC&#46; Unfortunately&#44; in a significant number of patients subsequent lines of therapy are required due to an inadequate response or a relapse after an initial response&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">17</span></a> Among the most recent therapeutic options&#44; TOFA has also shown its efficacy in UC patients who do not respond or lose response to TNF-&#945; antagonists achieving clinical remission rates of 18&#46;5&#37; and 16&#46;6&#37; after 8 weeks in the Oral Clinical Trials for Tofacitinib in Ulcerative Colitis &#40;OCTAVE&#41; induction 1 and 2 trials&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">8</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">In addition to its use in other inflammatory conditions as rheumatoid arthritis&#44; ocular Beh&#231;et&#39;s disease&#44; systemic lupus erythematosus or pustular psoriasis&#44; GMA is approved in Europe for inducing remission in patients with active UC and Crohn&#39;s disease&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">18</span></a> The usual GMA protocol generally consists in 1&#8211;2 sessions per week usually up to a total of 10 sessions&#44;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">11</span></a> with a length of 60&#8211;90<span class="elsevierStyleHsp" style=""></span>min per session&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">4&#8211;7&#44;19</span></a> Intensive GMA of bi-weekly sessions has been shown to be superior to weekly GMA in patients with refractory UC&#44; both in terms of remission rate and time to remission&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">20&#44;21</span></a> In our study&#44; almost 60&#37; of the patients received twice-weekly GMA sessions&#44; with a median number of 10 sessions and a median duration of 82<span class="elsevierStyleHsp" style=""></span>min per session&#46; In addition&#44; half of the patients received maintenance GMA&#44; reflecting the use of more intensive therapy in this highly refractory subset of patients&#46; However&#44; maintenance GMA still remains controversial&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">11</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">GMA has shown long-term benefit in patients with active UC and insufficient response or intolerance to immunosuppressants or biologics&#44; a difficult-to-treat patient subgroup&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">22</span></a> Its unique mechanism of action provides immunological effects that are expected to act synergistically when combined with more conventional agents for UC&#46; There are several studies and case series already showing promising results when combining GMA with different biologics like anti-TNF agents&#44; as well as with vedolizumab or ustekinumab&#46;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">5&#44;7&#44;11&#8211;13</span></a> Most of the evidence with this combination therapy has been described with biologics&#44; and its use with small molecules is still very limited&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">10</span></a> In our cohort&#44; partial Mayo score significantly decreased 1 and 6 months after the last GMA session&#44; although we did not observe significant changes in biomarkers&#46; Notably&#44; no patient required colectomy during follow-up&#59; all patients under steroids at baseline were able to stop them and only one patient required a new course of steroids&#46; This is in line with previous studies that have demonstrated the steroid-sparing effect of adsorptive GMA&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">23</span></a> Thus&#44; increasing evidence supports that GMA might be an attractive alternative in the setting of steroid-dependency even in patients receiving biologics and small molecules&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">11</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">Only one previous case series has described the feasibility of combining GMA with TOFA during the induction in patients with refractory UC&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">10</span></a> In seven patients who received twice-weekly concomitant sessions of GMA plus TOFA during the induction period&#44; 71&#46;4&#37; achieved clinical remission at 10 weeks&#46; The percentages of patients with mucosal healing and complete mucosal healing at 10 weeks were 100&#37; and 43&#37;&#44; respectively&#46; There were statistically significant changes in the full Mayo score and endoscopic subscore at 10 weeks compared to baseline&#46; Here&#44; Tanida et al&#46; concluded that combining intensive GMA plus TOFA was well tolerated and may be useful for inducing clinical remission in patients with refractory UC&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">10</span></a> It should be noted that&#44; in our study&#44; the strategy consisted in combining GMA with TOFA after PNR or LOR to this agent and not during the induction&#46; Moreover&#44; it could be expected that a more intensive GMA regimen might have improved the results observed in our cohort&#46; Despite these considerations&#44; both reports highlight the safety of this combination therapy and the possibility of improving outcomes in different scenarios of patients treated with small molecules&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">GMA selectively depletes activated leukocytes of the myeloid lineage&#44; mainly by removing neutrophils&#44; the most prominent cellular population during disease flares&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">11</span></a> Besides&#44; it has several secondary immunomodulatory effects&#44; including release of anti-inflammatory mediators&#44; decreased production of proinflammatory cytokines&#44; reduced neutrophil chemotaxis and endothelial cell adhesion&#44; down-regulation of circulating leukocyte cell surface proteins&#44; and induction of regulatory T and B-cells &#40;Tregs and Bregs&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">11&#44;24</span></a> Furthermore&#44; in the event of secondary LOR to anti-TNFs&#44; recent evidence suggests that GMA may contribute to re-establishing a treatment effect in a proportion of patients&#44;<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">11&#44;25</span></a> probably by reducing anti-drug antibodies and without an influence on trough levels&#46;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">13&#44;26</span></a> The exact mechanism of action of the combination of GMA with TOFA is still unknown and should be further explored&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">GMA is safe and well tolerated in the treatment of IBD in steroid-dependent cases and also in combination with biologics&#46;<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">11&#44;27&#44;28</span></a> In our population&#44; no patient reported any AE related to the combination therapy&#46; The low rate of surgery and the ability to reduce steroids with few AEs may allow to control the disease and the inflammatory process without switching the therapy in refractory patients with limited treatment options once they have already used TOFA&#46; Our results regarding the safety profile appear to be even better than the ones described by Tanida et al&#46;&#44; where three patients showed an AE mainly attributed to TOFA &#40;an orolabial herpes and temporary increase in creatinine phosphokinase and triglyceride&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">10</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">Our study has also some limitations that should be addressed&#46; The retrospective design and the variability of TOFA and GMA regimens may limit our ability to obtain more definite conclusions&#46; Though&#44; this study could serve as a basis for future clinical trials exploring the potential of combining GMA with TOFA in refractory UC patients with an inadequate response to this agent&#46; Further large prospective studies are expected to clarify the exact mechanisms underlying the beneficial effect of this strategy and define the characteristics of patients with the highest probability of responding to this strategy&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">In conclusion&#44; our results suggest the potential effectiveness&#44; safety and tolerability of combining GMA with TOFA in selected UC patients with an insufficient or inadequate response to this drug&#46; This approach could expand the number of therapeutic options available for some patients with refractory UC and deserves more research&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Authors&#8217; contributions</span><p id="par0125" class="elsevierStylePara elsevierViewall">IR-L and JLC&#58; study design&#44; data analysis and drafting the manuscript&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">FC&#44; EG&#44; CH&#44; EI&#44; EL&#44; YZ&#44; MB-A&#44; DG&#58; data collection&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">DG and JLC&#58; revised the manuscript for important intellectual content&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Ethical considerations</span><p id="par0140" class="elsevierStylePara elsevierViewall">Informed consent was obtained from all patients included in the study&#46; The study was approved by the local Ethics Committee of the coordinating center &#40;EPA2017050&#41;&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Funding</span><p id="par0145" class="elsevierStylePara elsevierViewall">IR-L is funded by a research grant from <span class="elsevierStyleGrantSponsor" id="gs1">Gobierno Vasco &#8211; Eusko Jaurlaritza</span> &#91;grant number <span class="elsevierStyleGrantNumber" refid="gs1">2020111061</span>&#93; and by a research grant from <span class="elsevierStyleGrantSponsor" id="gs2">Biobizkaia Health Research Institute</span> &#91;Grant No <span class="elsevierStyleGrantNumber" refid="gs2">BCB&#47;I&#47;LIB&#47;22&#47;008</span>&#93;&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Conflict of interest</span><p id="par0150" class="elsevierStylePara elsevierViewall">IR-L has received financial support for traveling and educational activities from or has served as an advisory board member for Abbvie&#44; Adacyte&#44; Celltrion&#44; Chiesi&#44; Danone&#44; Ferring&#44; Faes Farma&#44; Janssen&#44; Galapagos&#44; MSD&#44; Pfizer&#44; Roche&#44; Takeda&#44; and Tillotts Pharma&#46; Financial support for research&#58; Tillotts Pharma&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">YZ has received support for conference attendance&#44; speaker fees&#44; research support and consulting fees from AbbVie&#44; Adacyte&#44; Almirall&#44; Amgen&#44; Dr&#46; Falk Pharma&#44; FAES Pharma&#44; Ferring&#44; Janssen&#44; MSD&#44; Otsuka&#44; Pfizer&#44; Shire&#44; Takeda&#44; Galapagos&#44; Boehringer Ingelheim and Tillotts Pharma&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">MB-A has received financial support for traveling and educational activities from or has served as an advisory board member for Pfizer&#44; MSD&#44; Takeda&#44; AbbVie&#44; Kern&#44; Janssen&#44; Fresenius Kabi&#44; Galapagos&#44; Lilly&#44; BMS&#44; Faes Farma&#44; Chiesi and Adacyte&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">JLC has received financial support for traveling and educational activities from or has served as an advisory board member for Abbvie&#44; Adacyte&#44; Chiesi&#44; Ferring&#44; Janssen&#44; MSD&#44; Pfizer&#44; Takeda&#44; and Tillotts Pharma&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">The remaining authors have no conflicts of interest to declare&#46;</p></span></span>"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Granulocyte&#8211;monocyte apheresis &#40;GMA&#41; has shown to be safe and effective in treating ulcerative colitis &#40;UC&#41;&#44; also in combination with biologics&#46; The objective of this study is to evaluate the efficacy and safety of combining GMA after primary non-response &#40;PNR&#41; or loss of response &#40;LOR&#41; to tofacitinib &#40;TOFA&#41; in patients with UC&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Patients and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Retrospective study including all patients with refractory UC who received GMA plus TOFA&#46; Efficacy was assessed 1 and 6 months after finishing GMA by partial Mayo score&#44; C-reactive protein &#40;CRP&#41; and fecal calprotectin &#40;FC&#41;&#46; Descriptive statistics and non-parametric tests were used in the statistical analysis&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Twelve patients were included &#40;median 46 years &#91;IQR&#44; 37&#8211;58&#93;&#59; 67&#37; female&#59; 67&#37; E3&#41;&#46; Patients were mostly receiving TOFA 10<span class="elsevierStyleHsp" style=""></span>mg bid &#40;75&#37;&#41;&#44; and 33&#37; also concomitant steroids at baseline&#46; Median partial Mayo score at baseline was 7 &#40;IQR&#44; 5&#8211;7&#41;&#44; and it decreased to a median of 2 &#40;IQR&#44; 0&#8211;3&#41; and 0 &#40;IQR&#44; 0&#8211;3&#41; after 1 and 6 months &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;027 and 0&#46;020&#44; respectively&#41;&#44; while no differences were found in CRP and FC&#46; Clinical remission was achieved by 6 patients both at 1 &#40;50&#37;&#41; and 6 months &#40;67&#37;&#41;&#46; CF values<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>250<span class="elsevierStyleHsp" style=""></span>mg&#47;kg were achieved by 2 and 4 patients at 1 and 6 months &#40;data available in 5 and 7 patients&#44; respectively&#41;&#46; No patient required dose-escalation of TOFA&#44; and one patient was able to de-escalate the drug&#46; No patient required colectomy and all patients under steroids were able to stop them&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The combination of GMA and TOFA can be effective in selected cases of UC after PNR or LOR to this drug&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Objective"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Patients and methods"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
          ]
          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusion"
          ]
        ]
      ]
      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">La af&#233;resis de granulocitos-monocitos &#40;GMA&#41; ha demostrado ser segura y eficaz en el tratamiento de la colitis ulcerosa &#40;CU&#41;&#44; incluso en combinaci&#243;n con f&#225;rmacos biol&#243;gicos&#46; El objetivo de este estudio es evaluar la eficacia y la seguridad de combinar GMA con tofacitinib &#40;TOFA&#41; tras falta de respuesta primaria o p&#233;rdida de respuesta a este f&#225;rmaco en pacientes con CU&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Pacientes y m&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudio retrospectivo que incluy&#243; a todos los pacientes con CU refractaria que recibieron GMA m&#225;s TOFA&#46; La eficacia se evalu&#243; 1 y 6 meses despu&#233;s de finalizar la GMA mediante la puntuaci&#243;n de Mayo parcial&#44; la prote&#237;na C reactiva &#40;PCR&#41; y la calprotectina fecal &#40;CF&#41;&#46; El an&#225;lisis estad&#237;stico se realiz&#243; mediante par&#225;metros descriptivos y pruebas no param&#233;tricas&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se incluyeron doce pacientes &#40;mediana 46 a&#241;os &#91;RIQ&#44; 37-58&#93;&#59; 67&#37; mujeres&#59; 67&#37; E3&#41;&#46; En el momento basal&#44; la mayor&#237;a de los pacientes estaban recibiendo TOFA 10<span class="elsevierStyleHsp" style=""></span>mg dos veces al d&#237;a &#40;75&#37;&#41;&#44; y el 33&#37; tambi&#233;n recib&#237;an esteroides concomitantes&#46; La mediana de la puntuaci&#243;n de Mayo parcial basal fue de 7 &#40;RIC&#44; 5-7&#41;&#44; y disminuy&#243; a una mediana de 2 &#40;RIC&#44; 0-3&#41; y 0 &#40;RIC&#44; 0-3&#41; tras 1 y 6 meses &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;027 y 0&#44;020&#44; respectivamente&#41;&#44; mientras que no se encontraron diferencias en la PCR y la CF&#46; Se logr&#243; remisi&#243;n cl&#237;nica en 6 pacientes tanto al mes &#40;50&#37;&#41; como a los 6 meses &#40;67&#37;&#41;&#46; Dos y 4 pacientes alcanzaron valores de CF &#60;<span class="elsevierStyleHsp" style=""></span>250<span class="elsevierStyleHsp" style=""></span>mg&#47;kg el mes 1 y el 6 &#40;datos disponibles en 5 y 7 pacientes&#44; respectivamente&#41;&#46; Ning&#250;n paciente requiri&#243; aumentar la dosis de TOFA y un paciente pudo reducirla&#46; Ning&#250;n paciente necesit&#243; colectom&#237;a y todos los pacientes tratados con esteroides pudieron suspenderlos&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusi&#243;n</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">La combinaci&#243;n de GMA y TOFA puede ser eficaz en casos seleccionados de CU tras la falta de respuesta primaria o p&#233;rdida de respuesta a este f&#225;rmaco&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Objetivo"
          ]
          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "Pacientes y m&#233;todos"
          ]
          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Resultados"
          ]
          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclusi&#243;n"
          ]
        ]
      ]
    ]
    "multimedia" => array:4 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1184
            "Ancho" => 1550
            "Tamanyo" => 63568
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Clinical disease activity at baseline&#44; 1 month&#44; and 6 months &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>12&#41; after granulocyte and monocyte apheresis&#46; The partial Mayo score significantly decreased 1 and 6 months after the last apheresis session&#46; Results are expressed as mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#46;</p>"
        ]
      ]
      1 => 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:1 [
          "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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Variable&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">GMA plus tofacitinib<span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>12&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="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Age &#40;years&#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>Median &#91;IQR&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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 &#91;37&#8211;58&#93;&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="2" 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="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Sex&#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>Women&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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;67&#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="2" 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="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Smoking habit&#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>Never&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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;75&#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>Former smoker&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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;17&#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>Smoker&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" 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="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Disease location&#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>Left-sided colitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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;33&#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>Extensive colitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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;67&#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="2" 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="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Previous treatments&#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>Mesalazine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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&#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>Systemic steroids&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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&#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>Thiopurines&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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 &#40;83&#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>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">2 &#40;17&#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>Infliximab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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;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="elsevierStyleHsp" style=""></span>Adalimumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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;58&#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>Golimumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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></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>Ustekinumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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></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>Vedolizumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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;42&#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="2" 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-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">Concomitant steroids&#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">4 &#40;33&#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="2" 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="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Dose of tofacitinib&#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>5<span class="elsevierStyleHsp" style=""></span>mg bid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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;17&#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>10<span class="elsevierStyleHsp" style=""></span>mg bid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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;75&#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>15<span class="elsevierStyleHsp" style=""></span>mg bid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" 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="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Partial Mayo score at baseline</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>Median &#91;IQR&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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 &#91;5&#8211;7&#93;&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="2" 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="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">C-reactive protein at baseline &#40;mg&#47;L&#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>Median &#91;IQR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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;5&#8211;30&#93;&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="2" 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="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Fecal calprotectin at baseline &#40;mg&#47;kg&#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>Median &#91;IQR&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1013 &#91;757&#8211;2047&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                  <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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Characteristics&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">GMA plus tofacitinib<span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>12&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="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Indication of apheresis&#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>Primary failure&#47;partial response&nbsp;\t\t\t\t\t\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">8 &#40;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="elsevierStyleHsp" style=""></span>Secondary loss of response&nbsp;\t\t\t\t\t\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">4 &#40;33&#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="2" 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="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Type of primary nonresponse&#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>Partial response&nbsp;\t\t\t\t\t\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;88&#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>No response&nbsp;\t\t\t\t\t\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;12&#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="2" 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="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Number of sessions at induction</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>Median &#91;<span class="elsevierStyleItalic">Q</span>1&#44; <span class="elsevierStyleItalic">Q</span>3&#93;&nbsp;\t\t\t\t\t\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">10 &#91;7&#46;5&#8211;10&#93;&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>Range&nbsp;\t\t\t\t\t\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">4&#8211;10&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="2" 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="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Total number of sessions</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>Median &#91;<span class="elsevierStyleItalic">Q</span>1&#44; <span class="elsevierStyleItalic">Q</span>3&#93;&nbsp;\t\t\t\t\t\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">17 &#91;11&#8211;27&#93;&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="2" 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="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Frequency of sessions&#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>Weekly&nbsp;\t\t\t\t\t\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;17&#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>Twice-weekly&nbsp;\t\t\t\t\t\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">8 &#40;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="elsevierStyleHsp" style=""></span>Three times per week&nbsp;\t\t\t\t\t\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;17&#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="2" 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="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Filtered volume&#44; mL</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>Median &#91;IQR&#93;&nbsp;\t\t\t\t\t\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">1880 &#91;1800&#8211;2265&#93;&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>Range&nbsp;\t\t\t\t\t\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">1800&#8211;2700&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="2" 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="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Duration of sessions&#44; min</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>Median &#91;IQR&#93;&nbsp;\t\t\t\t\t\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">82<span class="elsevierStyleHsp" style=""></span>min &#40;63&#8211;90&#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>Range&nbsp;\t\t\t\t\t\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">45&#8211;90&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="2" 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-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">Maintenance apheresis&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 &#40;50&#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="2" 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="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Follow-up&#44; months</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>Median &#91;IQR&#93;&nbsp;\t\t\t\t\t\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">11 &#91;6&#8211;20&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Characteristics of the granulocyte and monocyte apheresis &#40;GMA&#41; treatment &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>12&#41; and duration of follow-up&#46;</p>"
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                  \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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Clinical outcome&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Response at 1 month&#44; median &#91;Q1&#44; Q3&#93;</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
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Partial Mayo score&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">2 &#91;0&#8211;4&#93;&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>Fecal calprotectin&#44; mg&#47;kg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">600 &#91;140&#8211;800&#93;&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="2" 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="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Response at 6 months&#44; median &#91;Q1&#44; Q3&#93;</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>Partial Mayo score&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">0 &#91;0&#8211;3&#93;&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>Fecal calprotectin&#44; mg&#47;kg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">244 &#91;85&#8211;510&#93;&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="2" 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="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Physician Global Assessment</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>No activity&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">6&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>Mild&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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&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
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Moderate&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Severe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">0&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="2" 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-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">Tofacitinib de-escalation&#44; N</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&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">New biologic or small-molecule&#44; N</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">4&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">Steroid withdrawal&#44; N</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">3&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">New steroid course&#44; N</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&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">Surgery&#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">0 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Clinical outcomes &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>12&#41;&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:28 [
            0 => array:3 [
              "identificador" => "bib0145"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Therapeutic leukocytapheresis for inflammatory bowel disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46;R&#46; Saniabadi"
                            1 => "H&#46; Hanai"
                            2 => "K&#46; Fukunaga"
                            3 => "K&#46; Sawada"
                            4 => "C&#46; Shima"
                            5 => "I&#46; Bjarnason"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.transci.2007.08.003"
                      "Revista" => array:7 [
                        "tituloSerie" => "Transfus Apher Sci"
                        "fecha" => "2007"
                        "volumen" => "37"
                        "paginaInicial" => "191"
                        "paginaFinal" => "200"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17974479"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0261561418325676"
                          "estado" => "S300"
                          "issn" => "02615614"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0150"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical evaluation of granulocyte&#47;monocyte apheresis therapy for active ulcerative colitis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "K&#46; Kanke"
                            1 => "M&#46; Nakano"
                            2 => "H&#46; Hiraishi"
                            3 => "A&#46; Terano"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.dld.2004.08.004"
                      "Revista" => array:6 [
                        "tituloSerie" => "Dig Liver Dis"
                        "fecha" => "2004"
                        "volumen" => "36"
                        "paginaInicial" => "811"
                        "paginaFinal" => "817"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15646427"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0155"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Processed blood volume impacts clinical efficacy in patients with ulcerative colitis undergoing adsorptive depletion of myeloid lineage leucocytes"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "N&#46; Yoshimura"
                            1 => "T&#46; Tadami"
                            2 => "T&#46; Kawaguchi"
                            3 => "M&#46; Sako"
                            4 => "H&#46; Yoshimoto"
                            5 => "T&#46; Yamaka"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00535-011-0464-0"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Gastroenterol"
                        "fecha" => "2012"
                        "volumen" => "47"
                        "paginaInicial" => "49"
                        "paginaFinal" => "55"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21915624"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
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                ]
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            3 => array:3 [
              "identificador" => "bib0160"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
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