Biological treatment interruption in inflammatory bowel disease: Motivation and predictive factors

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"apellidos" => "Pericàs" ] 15 => array:1 [ "colaborador" => "on behalf of the PRECISED consortium" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0210570522002734?idApp=UINPBA00004N" "url" => "/02105705/0000004600000009/v1_202310250510/S0210570522002734/v1_202310250510/en/main.assets" ] "itemAnterior" => array:18 [ "pii" => "S0210570522002552" "issn" => "02105705" "doi" => "10.1016/j.gastrohep.2022.10.014" "estado" => "S300" "fechaPublicacion" => "2023-11-01" "aid" => "2007" "copyright" => "Elsevier España, S.L.U." 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Description: Questionnaire model used in our Motility Unit following international guidelines recommendations." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Ariadna Aguilar, Jordi Serra" "autores" => array:2 [ 0 => array:2 [ "nombre" => "Ariadna" "apellidos" => "Aguilar" ] 1 => array:2 [ "nombre" => "Jordi" "apellidos" => "Serra" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0210570522002552?idApp=UINPBA00004N" "url" => "/02105705/0000004600000009/v1_202310250510/S0210570522002552/v1_202310250510/en/main.assets" ] "en" => array:22 [ "idiomaDefecto" => true "cabecera" => "Original article" "titulo" => "Biological treatment interruption in inflammatory bowel disease: Motivation and predictive factors" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "671" "paginaFinal" => "681" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "María Rocío Davis González, María Pilar Ballester, Eva Romero-González, Ana María Sánchez-Pardo, David Marti-Aguado, Joan Tosca, Carles Suria, Rosario Antón Ausejo, Isabel Pascual Moreno, María Dolores Planelles Silvestre, Miguel Mínguez Pérez, Marta Maia Bosca-Watts" "autores" => array:12 [ 0 => array:3 [ "nombre" => "María Rocío" "apellidos" => "Davis González" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "d" "identificador" => "fn0005" ] ] ] 1 => array:4 [ "nombre" => "María Pilar" "apellidos" => "Ballester" "email" => array:1 [ 0 => "mapibafe@gmail.com" ] "referencia" => array:4 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "d" "identificador" => "fn0005" ] 3 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 2 => array:3 [ "nombre" => "Eva" "apellidos" => "Romero-González" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "Ana María" "apellidos" => "Sánchez-Pardo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 4 => array:3 [ "nombre" => "David" "apellidos" => "Marti-Aguado" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 5 => array:3 [ "nombre" => "Joan" "apellidos" => "Tosca" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 6 => array:3 [ "nombre" => "Carles" "apellidos" => "Suria" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 7 => array:3 [ "nombre" => "Rosario" "apellidos" => "Antón Ausejo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 8 => array:3 [ "nombre" => "Isabel" "apellidos" => "Pascual Moreno" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 9 => array:3 [ "nombre" => "María Dolores" "apellidos" => "Planelles Silvestre" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 10 => array:3 [ "nombre" => "Miguel" "apellidos" => "Mínguez Pérez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 11 => array:3 [ "nombre" => "Marta Maia" "apellidos" => "Bosca-Watts" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "IBD Unit, Digestive Disease Medicine, University of Valencia, University Clinic Hospital of Valencia, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Instituto de Investigación Sanitaria INCLIVA, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Histocompatibility Laboratory, Transfusion Center of Valencian Community, Valencia, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Interrupción del tratamiento biológico en la enfermedad inflamatoria intestinal: causas y factores predictores" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1934 "Ancho" => 1675 "Tamanyo" => 179084 ] ] "descripcion" => array:1 [ "en" => "(A) Secondary loss of response in IBD patients treated with adalimumab without immune-modulator. (B) Secondary loss of response in CD patients treated with adalimumab." ] ] ] "textoCompleto" => "IntroductionIBD is a chronic disease whose treatment is sometimes complex because there is no established marker to indicate which treatments will work better on each patient. In the past years, studies have been performed to determine response-related factors, with recent interest in genetic predisposition to explain loss of response.<a class="elsevierStyleCrossRef" href="#bib0160">1</a> Development of antiTNF-α antibodies (immunogenicity) has been related to the loss-of-response to antiTNF drugs and to the development of side effects.<a class="elsevierStyleCrossRefs" href="#bib0165">2–5</a> Based on this, some authors link response to biologics and tolerance to having the HLA-DQ A1*05 allele, and have therefore proposed determining this allele to decide what to prescribe.<a class="elsevierStyleCrossRefs" href="#bib0165">2,3,5</a>Besides genetics, other factors such as the amount of inflammation may influence response to biologic treatment and, therefore, treatment duration. This depends on disease extension,<a class="elsevierStyleCrossRef" href="#bib0185">6</a> flare severity,<a class="elsevierStyleCrossRef" href="#bib0160">1</a> having perianal disease<a class="elsevierStyleCrossRef" href="#bib0190">7</a> or extraintestinal symptoms.<a class="elsevierStyleCrossRef" href="#bib0160">1</a> The type of biologic that is used<a class="elsevierStyleCrossRef" href="#bib0195">8</a> and co-treatments<a class="elsevierStyleCrossRefs" href="#bib0200">9,10</a> also play an important role in therapeutic response, as well as side effects that may lead to treatment interruption. Nevertheless, the interaction of genetic, clinical and therapeutic factors on the risk of treatment interruption has not been widely studied, and even less with the most recent biological drugs.Our hypothesis was that biological treatment discontinuation depends not only on HLA-DQA1*05, but also, and more importantly, on clinical and therapeutic factors in real-life-practice. Our objective was to evaluate the influence of clinical and therapeutic factors, along with HLA, in biological treatment discontinuation.Materials and methodsStudy design and patient populationAn observational, retrospective with prospectively gathered data, single-center, cohort study was performed. All consecutive patients with IBD diagnosis, followed in the IBD Unit of the Clinic University Hospital of Valencia, Spain, from 2007 until 2011 were screened for eligibility. Inclusion criteria were: firm IBD diagnosis, age >18 years and, at least, a single exposure to biological drugs (infliximab -IFX-, adalimumab -ADA-, vedolizumab -VDZ- or ustekinumab -USTE-). Patients with irregular follow-up or non-adherent according to medical criteria, were excluded.Data collection and follow-upData were collected from our single-center ENEIDA registry. The ENEIDA Registry is a prospectively maintained database of IBD patients of the Spanish Crohn's and Colitis Work Group (GETECCU), initiated in 2006. This registry includes demographic, clinical, endoscopic and therapeutic data. Patients were followed from date of diagnosis until date of death, last visit or study closure in December 2020.Variables included when biological drug initiation were: age, sex, IBD type, phenotypic expression of the disease, extraintestinal manifestations, complications, type of biological treatment, previous biological treatments (or naïve), concomitant immune-modulators and disease duration.Treatment discontinuation as the main outcome was recorded at any time during follow-up, including motivation for withdrawal and duration of treatment.DefinitionsDiagnosis of IBD was made by local gastroenterologists based on standard clinical, endoscopic, and pathological criteria according to the European Crohn's and Colitis Organization (ECCO) consensus guidelines.<a class="elsevierStyleCrossRef" href="#bib0210">11</a> Disease extent was determined with ileocolonoscopy and classified according to the Montreal classification.<a class="elsevierStyleCrossRef" href="#bib0215">12</a> The maximum extent of disease at any time since diagnosis until biological treatment initiation was assigned for each patient. The extraintestinal manifestations taken into account were peripheral arthropathy, ankylosing spondylitis, sacroilitis, cutaneous (erythema nodosum or pyoderma gangrenosum), aphthous stomatitis, ophthalmic (iritis or episcleritis), primary sclerosing cholangitis and thrombosis. Complications considered were megacolon, major acute hemorrhage defined as hematochezia or melena with hemodynamic instability (hypotension or orthostatic change in vital signs) and/or an acute decrease in hemoglobin concentration of at least 2mg/dL compared with baseline, bowel perforation or intra-abdominal abscesses. Irregular follow-up was considered when the patient did not attend two consecutive appointments.Biological treatment regimen for IBD was the same in all patients, based on Spanish-developed guidelines, which is in agreement with ECCO guidelines.<a class="elsevierStyleCrossRefs" href="#bib0220">13,14</a> Patients were regularly monitored at the IBD Unit and intensification of treatment was performed taking into account both symptoms and drug levels. Medication exposure was defined as the administration of, at least, one dose of an IBD-related drug. Disease activity at the time of biological drug initiation was assessed based on the Harvey–Bradshaw index<a class="elsevierStyleCrossRef" href="#bib0230">15</a> or partial Mayo score,<a class="elsevierStyleCrossRef" href="#bib0235">16</a> calprotectin levels and/or endoscopy activity evaluated with endoscopic SESCD,<a class="elsevierStyleCrossRef" href="#bib0240">17</a> Mayo score<a class="elsevierStyleCrossRef" href="#bib0235">16</a> or Rutgeerts<a class="elsevierStyleCrossRef" href="#bib0245">18</a> when available. Treatment discontinuation included the interruption of medication due to primary non-response (PNR), secondary loss of response (SLR) or adverse events (AE). PNR was considered when lack of response during the first 16 weeks after initiation of biological drug, despite intensification or modifications in concomitant drugs, led to the suspension of treatment. SLR was taken into account when the appearance of symptoms or intestinal inflammation assessed by an elevated calprotectin or activity on endoscopy, led to the suspension of treatment throughout follow-up. AE were categorized into immune-mediated (infusion reactions, flu-like syndrome, chronic hypersensitivity and paradoxical reactions), infections, neoplasms, hematological toxicity and others (including those unspecific or not described but that had a temporary association with the drug and remitted when it was discontinued).<a class="elsevierStyleCrossRef" href="#bib0250">19</a>Genotypic analysisHLA-DQA1 low and high-resolution genotyping was performed by polymerase chain reaction with sequence-specific primers according to the method described by Olerup et al.<a class="elsevierStyleCrossRef" href="#bib0255">20</a> Genomic DNA was isolated from nucleated cells by Magtration® technology.<a class="elsevierStyleCrossRef" href="#bib0260">21</a> Each PCR reaction was performed on about 80ng of extracted DNA, using 0.15 units of Taq DNA polymerase (AmpliTaq® DNA Polymerase, Applied Biosystems, The Netherlands), and Olerup commercial primers (Olerup SSP AB, Stockholm, Sweden), according to the manufacturer's instructions. PCR was carried out in a final volume of 10μL in a GeneAmp PCR System 9700 (Applied Biosystems, The Netherlands). An initial denaturizing step at 94°C for 2min was followed by 10 two-temperature cycles (94°C for 10s and 65°C for 60s) and 20 three-temperature cycles (94°C for 10s, 61°C for 50s and 72°C for 30s). Detection of amplified alleles was carried out by agarose gel electrophoresis.Statistical analysisQualitative variables were expressed as frequencies (%) and quantitative variables as mean and standard deviation (SD) or median and interquartile range (IQR). Univariate analysis was performed to compare genetic factors, demographic variables, phenotypic expression, extraintestinal manifestations, complications, concomitant treatments and type of biological drugs with treatment discontinuation. Comparison between groups was made using the t-test or Mann–Whitney U test for continuous data and the chi-square test or Fisher's test for categorical data, as required. Measures of association between qualitative variables were reported as odds ratio (OR) with 95% confidence intervals (95% CI). Time-to-treatment discontinuation was calculated with the Kaplan–Meier curve from the date of biological treatment initiation to the date of biological drug withdrawal, death or study closure, whichever came first. Cox proportional hazard regression was used to evaluate the independent contribution of each factor on time-to-treatment interruption. These results were expressed as hazard ratios (HR) with respective 95% CI. All statistical tests were two-sided. A p value of <0.05 was considered statistically significant. Covariates showing a clinical and statistical significance or participating as a confounding factor for the variable of interest were included in the multivariable models. All analyses were performed with the SPSS V22.0 software package.ResultsStudy populationWe had determined HLA-DQ A1*05 on 457 consecutive patients of which 150 were eligible because they were on biologics (108 CD and 42 UC, <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>): 91 (61%) males and 59 (39%) females. The median age at IBD diagnosis was 26 in CD patients and 28 in UC patients. Mean follow-up from date of diagnosis was 21 (SD 7) years.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>Patients characteristics according to HLA-DQA1*05Prevalence of HLA-DQA1*05 was 40% (95% CI=32–48) in the total population (14% with two HLA DQ-A1*05 alleles), with a prevalence of 38% (95% CI=23–53) in UC and 41% (95% CI=31–50) in CD (p=0.766). A higher proportion of extensive UC (OR=1.8; 95% CI=1.4–2.5; p=0.033) and a tendency to present more CD with perianal involvement (p=0.059) were observed in cases with positive HLA-DQA1*05 (<a class="elsevierStyleCrossRef" href="#sec0105">Supplementary Table 1</a>). There were no significant differences in follow-up between patients with or without positive HLA-DQA1*05 (22±8 vs. 20±7; p=0.073).Biological regimensA total of 312 biological treatments were administered (219 in CD and 93 in UC) during follow-up. Median number of biological drugs received by patient was 2 (IQR 1–3), in both CD and UC patients. A higher proportion of naïve patients received IFX with respect to non-naïve (63% vs. 29%; OR=4.170; 95% CI=2.6–6.7; p<0.001) while more non-naïve patients were treated with ADA (41% vs. 30%; OR=0.615; 95% CI=0.381–0.991; p=0.045), VDZ (13% vs. 2%; OR=0.100; 95% CI=0.023–0.431; p<0.001) or USTE (18% vs. 6%; OR=0.298; 95% CI=0.133–0.671; p=0.002), both in CD and UC. Similarly, associated immune-modulator (IMM) treatment was more frequent in patients that received IFX (51% vs. 39%; OR=1.684; 95% CI=1.060–2.677; p=0.027) while no significant differences were observed with ADA (33% vs. 38%; OR=0.787; 95% CI=0.485–1.275; p=0.333), VDZ (8% vs. 9%; OR=0.873; 95% CI=0.376–2.026; p=0.751) or USTE (9% vs. 15%; OR=0.594; 95% CI=0.285–1.240; p=0.162). The main indication for a biological drug was disease flare, and this group of patients had a significantly higher probability of receiving IFX (89% vs. 76%; OR=2.567; 95% CI=1.357–4.855; p=0.003) and lower of ADA (72% vs. 87%; OR=0.408; 95% CI=0.228–0.728; p=0.002). Biological treatments according to genotypic analysis is described in <a class="elsevierStyleCrossRef" href="#sec0105">Supplementary Table 2</a>.Motivation for biological treatment discontinuationOf the 312 biological drugs, 147 (47%) were discontinued during study follow-up. The cumulative probability of treatment discontinuation was 30%, 41% and 56% at 1, 2 and 5 years of biological treatment initiation.The reasons for treatment discontinuation were loss of response and AE in 79 (25%) and 68 (22%) of biologic treatment, respectively, without significant differences in patients with and without positive HLA-DQA1*05 (p=0.241). Mean time for biological treatment discontinuation was significantly lower in patients with SLR (22 –95% CI=17–27 – vs. 59 – 95% CI=50–68 – months; log rank=22.554; p<0.001) or AE (23 – 95% CI=16–30 – vs. 59 – 95% CI=50–68 – months; log rank=42.753; p<0.001).Risk factors for treatment discontinuationRisk factors for treatment discontinuation are shown in <a class="elsevierStyleCrossRefs" href="#tbl0005">Tables 1–3</a>, for all the cases, patients with CD and patients with UC, respectively.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia>Anti-TNF therapy was associated with treatment discontinuation (OR=2.250; 95% CI=1.266–3.999; p=0.005), mainly with IFX (OR=1.682; 95% CI=1.070–2.643; p=0.024). Shorter disease duration at the time of biological treatment initiation was associated with higher treatment interruption (OR=0.931; 95% CI=0.903–0.961; p<0.001). Some of the extraintestinal manifestations were also associated with biological drug discontinuation, including peripheral arthropathy (OR=1.630; 95% CI=1.026–2.590; p=0.038); ankylosing spondylitis (OR=4.750; 95% CI=1.726–13.070; p=0.001) or sacroilitis (OR=4.916; 95% CI=1.605–15.062; p=0.002). Multivariable analysis including significant factors of the univariable analyses and HLA-DQ A1*05 kept IFX therapy, disease duration and extraintestinal manifestations as significant factors of treatment discontinuation while HLA-DQA1*05 did not show significant influence (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).In patients with CD, HLA-DQA1*05 positive had a higher risk of treatment discontinuation in univariable analyses (p=0.027). Treatment discontinuation was also associated with IFX and several extraintestinal manifestations (peripheral arthropathy, ankylosing spondylitis, sacroilitis and cutaneous manifestations). Multivariable analysis kept IFX therapy, spondylitis and sacroileitis as significant factors of treatment discontinuation, but no HLA-DQ (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).Cause and time-to-treatment interruptionA higher proportion of PNR was seen in patients with UC than with CD (HR=4.998; 95% CI=1.707–14.629; p=0.003), mainly associated with extensive colitis (HR=3.680; 95% CI=1.334–10.150; p=0.012). Only disease flare as indication of biological treatment was associated to shorter time-to-discontinuation due to SLR (HR=2.315; 95% CI=1.051–5.099; p=0.037) while HLA-DQA1*05 did not show significant influence (HR=1.231; 95% CI=0.757–2.005; p=0.400).A higher risk of AE was observed in patients with two alleles of HLA-DQA1*05 (46% vs. 25%; OR=2.551; 95% CI=1.325–4.911; p=0.004), spondylitis (46% vs. 26%; OR=2.403; 95% CI=1.032–5.594; p=0.037) or on anti-TNF therapy (32% vs. 11%; OR=3.987; 95% CI=1.742–9.125; p=0.001). Among anti-TNF drugs, mainly IFX was associated to AE (37% vs. 21%; OR=2.197; 95% CI=1.326–3.639; p=0.002), most commonly immune-mediated (27% vs. 12%; OR=2.746; 95% CI=1.516–4.976; p=0.001) and specially the paradoxical ones (14% vs. 5%; OR=3.368; 95% CI=1.194–9.506; p=0.028). Time-to-discontinuation of biological treatment due to AE was shorter with IFX therapy (HR=2.459; 95% CI=1.482–4.080; p<0.001) or spondylitis (49 vs. 112 months; HR=2.459; 95% CI=1.778–6.896; p<0.001) while two alleles of HLA-DQA1*05 did not show significant influence (HR=1.619; 95% CI=0.904–2.898; p=0.105) in the multivariable cox-proportional analyses.Treatment discontinuation according to the biological regimenFocusing on ADA treatment, cases with HLA-DQA1*05 showed shorter time-to-treatment withdrawal due to SLR (HR=2.255; 95% CI=1.070–4.754; p=0.033). This influence of HLA-DQA1*05 on time-to discontinuation of ADA therapy was only seen in patients without concomitant IMM treatment (HR=2.803; 95% CI=1.134–6.926; p=0.026) (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>A) or with CD (HR=3.492; 95% CI=1.388–8.783; p=0.008) (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>B) but it was not present in patients with IMM (HR=1.483; 95% CI=0.397–5.537; p=0.557) or with UC (HR=0.781; 95% CI=0.157–3.895; p=0.763). Multivariable cox proportional regression analyses maintained HLA-DQA1*05 (HR=2.484; 95% CI=1.171–5.273; p=0.018) and disease flare as indication for ADA (HR=4.728; 95% CI=1.355–16.502; p=0.015) as independent predictors of SLR. No significant influence of HLA-DQA1*05 was seen with IFX (HR=0.855; 95% CI=0.399–1.885; p=0.698), USTE (HR=1.001; 95% CI=0.222–4.507; p=0.999) or VDZ (HR=0.591; 95% CI=0.066–5.291; p=0.638) on time-to discontinuation due to SLR.<elsevierMultimedia ident="fig0010"></elsevierMultimedia>DiscussionTreatment of IBD must be personalized. In order to give or interrupt treatment, several aspects must be regarded: genetics, type of IBD, phenotype of disease, extraintestinal manifestations, indication of treatment and the inflammatory burden.<a class="elsevierStyleCrossRef" href="#bib0160">1</a> About one third of the patients do not respond to AntiTNF-α induction (20–40% of CD and 30–40% UC patients)<a class="elsevierStyleCrossRef" href="#bib0265">22</a> and another third of the patients lose response during maintenance treatment (CD shows an annual SLR to IFX of 13%<a class="elsevierStyleCrossRef" href="#bib0270">23</a> and of 20% with ADA<a class="elsevierStyleCrossRef" href="#bib0275">24</a>).Several studies have demonstrated that HLA-DQA1*05 is related to the development of antibodies against antiTNF drugs and to the SLR to antiTNF,<a class="elsevierStyleCrossRefs" href="#bib0165">2–5</a> which could be something to keep in mind when starting biologics. In clinical practice, being able to maintain treatment, despite immunogenicity, certain AE, or a loss of response, is a goal that can be solved with treatment modifications such as intensifications or adding IMM. We are frequently treating young patients that will need to be on biologics (intermittently or continuously) all their life, so maintenance is crucial, which is why we decided to use treatment discontinuation as the main outcome of our study. In concrete, we focused our analysis on the “negative” reasons for stopping treatment (loss of response or side effects), not those that were based on interrupting due to remission or the patient's will to stop.In 2020, Sazonovs et al., published a study in which they had included 1240 CD naïve patients treated with IFX or ADA for a flare; they demonstrated that having one allele of HLA-DQ A1*05 conferred a double risk of developing anti-TNF antibodies.<a class="elsevierStyleCrossRef" href="#bib0180">5</a> That same year, Wilson et al. published the results of a retrospective study of 262 CD patients treated with IFX in which they had evaluated the relationship between HLA-DQA1*05 and developing anti-TNF antibodies. 79% of the people that had at least one HLA-DQA1*05 allele developed anti-TNF antibodies, with a significantly higher risk than patients without the allele.<a class="elsevierStyleCrossRef" href="#bib0175">4</a> Rodriguez-Alonso et al., carried out a retrospective study of 64 patients treated with IFX, who had been controlled until SLR. The multivariable analysis showed that having HLA-DQ A1*05 was the only factor associated to SLR.<a class="elsevierStyleCrossRef" href="#bib0165">2</a> In two retrospective studies with small samples of patients (53 and 20 patients), the same group observed that HLA-DQ A1*05 was only significant in SLR of patients on ADA,<a class="elsevierStyleCrossRef" href="#bib0170">3</a> and not on USTE.<a class="elsevierStyleCrossRef" href="#bib0280">25</a>In our study, we observed that HLA-DQ A1*05 was related to a more frequent and earlier treatment withdrawal due to SLR in CD patients on ADA without IMM. Patients with combotherapy of ADA and IMM did not show this difference, probably due to a reduction in immunogenicity, as the mentioned studies suggested. Similar to studies such as Camps et al.’s,<a class="elsevierStyleCrossRef" href="#bib0170">3</a> we observed the effect of this allele only in CD patients.We also looked into the relationship of HLA and clinical factors. Extensive colitis has a higher inflammatory burden and is related to an increased risk of colectomy due to biological treatment failure.<a class="elsevierStyleCrossRef" href="#bib0185">6</a> In agreement with previous results, we observed that extensive colitis was significantly associated with treatment interruption due to PNR. Similarly, indicating biologics for a flare of the disease was significantly associated with SLR, probably associated with more activity than when treatment is prescribed for remission maintenance or to prevent postoperative recurrence. At the same time, all of the UC patients that had at least one HLA-DQ A1*05 allele had extensive colitis and a statistically significant higher Mayo score (<a class="elsevierStyleCrossRef" href="#sec0105">Supplementary Tables 1 and 2</a>), suggesting that in UC population, HLA-DQ A1*05 may be associated with more active and extensive colitis, which was recently also observed in Nowak's pediatric population.<a class="elsevierStyleCrossRef" href="#bib0285">26</a>With respect to the number of treatments the patient has received in relation to loss of response, ADA has previously demonstrated efficacy and safety in UC and CD naïve and not-naïve to biologics,<a class="elsevierStyleCrossRef" href="#bib0195">8</a> although a considerably higher remission rate has been observed in patients who had not received IFX before being on ADA.<a class="elsevierStyleCrossRef" href="#bib0290">27</a> We did not observe general differences in SLR according to being naïve or not. The IFX group had a higher proportion of naïve patients, whereas the ADA group had a similar distribution of naïve vs. not naïve patients, with an important number of patients who had failed with IFX (generally SLR). Since the ADA group is where we obtained a relationship between the HLA-DQA1*05 and an increased SLR, genetics might be more relevant in non-naïve patients to set a daily-practice habit of associating IMM in second-line anti-TNF who are HLA-DQA1*05 positive.Several studies have observed fewer infusion reactions, with less anti-IFX antibody formation, combining IFX and azathioprine.<a class="elsevierStyleCrossRef" href="#bib0205">10</a> Studies with ADA are less clear, although a better response to induction treatment when combined with an IMM has been shown.<a class="elsevierStyleCrossRefs" href="#bib0290">27,28</a> When immunosuppression was analyzed with respect to PNR and SLR in both groups together (IFX and ADA), no differences were observed. However, a significantly earlier SLR was found in HLA-DQA1*05 positive patients treated with ADA alone, which was lost when an IMM was associated. As we previously mentioned on naïve and non-naïve patients treated with ADA, this might suggest that combotherapy with ADA and an IMM is probably especially useful in patients with this allele, to avoid early SLR.The SUSTAIN study showed that loss of response with USTE was related to a high Harvey Bradshaw baseline index, and unrelated to concomitant IMM.<a class="elsevierStyleCrossRef" href="#bib0300">29</a> We had 40 patients who had been on USTE. In line with what has been published,<a class="elsevierStyleCrossRef" href="#bib0280">25</a> we did not find any relationship between having HLA-DQA1*05, SLR and USTE, regardless of them being naïve or not, or being on concomitant IMM.Amiot et al. demonstrated that one third of the patients treated with VDZ had SLR, especially CD patients.<a class="elsevierStyleCrossRef" href="#bib0305">30</a> We have not found any study addressing the relationship between HLA-DQA1*05 and loss of response or AE. We did not observe any relationship between this allele or any of the factors we studied with SLR. However, the sample was small (26 patients) and further research is needed to confirm that HLA-DQA1*05 does not influence response to VDZ.Paradoxical reactions are more frequent with anti-TNF but also appear with other biologics. The SUSTAIN trial reported AE in 25 (7%) of the patients treated with USTE, mainly arthralgia and infections, with two cases of psoriasis.<a class="elsevierStyleCrossRef" href="#bib0300">29</a> With respect to VDZ, a cohort study published in 2018 described skin and joint reactions/side effects, which included 11 psoriasis. Eight of the 14 that had cutaneous reactions, had also presented them with anti-TNF-α.<a class="elsevierStyleCrossRef" href="#bib0310">31</a> In our study, IFX and spondylitis were significantly associated with treatment interruption due to AE. They were also related to the development of paradoxical reactions, as well as having two HLA-DQA1*05 alleles. Our study is in accordance with what has been published, because IFX is the most immunogenic of the biologics we have included.<a class="elsevierStyleCrossRef" href="#bib0250">19</a> Spondylitis is an extraintestinal manifestation with considerable genetic background. Up to 75% of CD patients with spondylitis are HLA-B27 positive.<a class="elsevierStyleCrossRef" href="#bib0160">1</a> Spondylitis is more frequent in colonic and perianal CD, and the risk of presenting it increases with disease duration and inflammatory burden.<a class="elsevierStyleCrossRef" href="#bib0160">1</a> Many mechanisms have been proposed to explain why spondylitis occurs in IBD. One would be the appearance of antibodies and circulating immune complexes against common epitopes in different locations: colon, eyes, skin, joints and biliary epithelium.<a class="elsevierStyleCrossRef" href="#bib0160">1</a> This has not been demonstrated, but it would explain the association we found between spondylitis and paradoxical reactions, because they would share the same mechanism of action. Genetic predisposition (mainly having two HLA-DQ A1*05 alleles) could be the basis of both mechanisms. In our study, CD patients with spondylitis had a tendency to carry one HLA-DQA1*05 allele (p=0.059), with a statistically significant difference if they had two HLA-DQ A1*05 alleles (p=0.010).Our study has two main strong points that should be mentioned: we studied not only CD but also UC patients in whom HLA-DQ A1*05 has barely been analyzed, and considered not only anti-TNF, but also USTE and VDZ (the latter which, to our knowledge, has not been analyzed yet). These two points will probably be useful in clinical practice, a part from the reinforcement of taking HLA-DQA1*05 into account when prescribing ADA without IMM. In addition, we have studied treatments instead of patients so that we could correctly analyze first or second/third-line treatments. On the other hand, the limitations of the study are that, although data has been prospectively gathered, the analysis is retrospective, and that some of the subanalysis have a small sample size (for example with VDZ). Despite these limitations, the results are relevant because there are few studies that directly contribute to personalize medicine using HLA-DQ.In conclusion, according to our results, HLA-DQA1*05 is relevant in SLR of IBD patients treated with ADA without IMM. In CD and UC patients treated with other biologics (IFX, USTE and VDZ), clinical factors associated with higher inflammatory activity were more important for treatment interruption, mainly extensive UC, extraintestinal manifestations and having indicated the biologic for a flare. Being on IFX, having associated spondylitis and carrying two HLA-DQ A1*05 alleles, were related to the appearance of paradoxical reactions (psoriasis, arthritis, suppurative hidradenitis and systemic erythematosus lupus) that let to treatment interruption.Our results support some of the published data from other groups, and offer a new point of view suggesting that a combination of genetic and clinical factors can guide our treatment decisions. We would need prospective studies, with bigger simple sizes, to confirm our results.SummaryWe present a retrospective study of Inflammatory Bowel Disease (IBD) patients. Our aim was to evaluate the influence of HLA-DQ A1*05, along with other clinical and therapeutic factors, in biological treatment discontinuation due to loss of response or adverse events.Ethical considerationsInformed consent to participate in our database was obtained from all patients. The study was approved by the institutional ethics committee of the hospital on 2021. The study complies with the principles of Good Clinical Practice and the Helsinki Declaration.Conflict of interestMaría Rocío Davis González declares educational activities sponsored by MSD, Ferring, Abbvie, Janssen and Takeda.Maria Pilar Ballester is supported by a Río Hortega award (CM19/00011), Instituto de Salud Carlos III (Spanish Ministry of Science and innovation).Carles Suria declares educational activities and research projects sponsored by Ferring, Abbvie, Janssen and AztraZeneca.David Marti-Aguado is recipient of a Río Hortega award (CM19/00212), Instituto de Salud Carlos III (Spanish Ministry of Science and innovation).Miguel Mínguez Pérez has served as a speaker, a consultant, and advisory member for or has received research funding from MSD, Abbvie, Pfizer, Janssen, Shire Pharmaceuticals, Allergan.Marta Maia Bosca-Watts declares educational activities, research projects, scientific meetings and advisory boards sponsored by MSD, Ferring, Abbvie, Janssen, Biogen and Takeda.The other authors declare no financial disclosures or conflicts of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:13 [ 0 => array:3 [ "identificador" => "xres1995885" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1712427" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1995884" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1712426" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Materials and methods" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Study design and patient population" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Data collection and follow-up" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Definitions" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Genotypic analysis" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Statistical analysis" ] ] ] 6 => array:3 [ "identificador" => "sec0040" "titulo" => "Results" "secciones" => array:7 [ 0 => array:2 [ "identificador" => "sec0045" "titulo" => "Study population" ] 1 => array:2 [ "identificador" => "sec0050" "titulo" => "Patients characteristics according to HLA-DQA1*05" ] 2 => array:2 [ "identificador" => "sec0055" "titulo" => "Biological regimens" ] 3 => array:2 [ "identificador" => "sec0060" "titulo" => "Motivation for biological treatment discontinuation" ] 4 => array:2 [ "identificador" => "sec0065" "titulo" => "Risk factors for treatment discontinuation" ] 5 => array:2 [ "identificador" => "sec0070" "titulo" => "Cause and time-to-treatment interruption" ] 6 => array:2 [ "identificador" => "sec0075" "titulo" => "Treatment discontinuation according to the biological regimen" ] ] ] 7 => array:2 [ "identificador" => "sec0080" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0085" "titulo" => "Summary" ] 9 => array:2 [ "identificador" => "sec0090" "titulo" => "Ethical considerations" ] 10 => array:2 [ "identificador" => "sec0095" "titulo" => "Conflict of interest" ] 11 => array:2 [ "identificador" => "xack698220" "titulo" => "Acknowledgments" ] 12 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2022-08-04" "fechaAceptado" => "2022-10-18" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1712427" "palabras" => array:5 [ 0 => "Inflammatory bowel disease" 1 => "HLA-DQ A1*05" 2 => "Biological drugs" 3 => "Secondary loss of response" 4 => "Adverse events" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1712426" "palabras" => array:5 [ 0 => "Enfermedad inflamatoria intestinal" 1 => "HLA-DQA1*05" 2 => "Biológicos" 3 => "Pérdida secundaria de respuesta" 4 => "Efectos adversos" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "BackgroundLoss-of-response and adverse events (AE) to biologics have been linked to HLA-DQA1*05 allele. However, the clinical factors or biologic used may influence treatment duration. Our objective was to evaluate the influence of clinical and therapeutic factors, along with HLA, in biological treatment discontinuation. MethodsA retrospective study of consecutive IBD patients treated with biologics between 2007 and 2011 was performed. Main outcome was treatment discontinuation due to primary non-response (PNR), secondary loss of response (SLR) or AE. HLA-DQA1 genotyping was done in all patients. Regression analyses were used to assess risk factors of treatment discontinuation. ResultsOne hundred fifty patients (61% male) with 312 biologic treatments were included. 147 (47%) were discontinued with a cumulative probability of 30%, 41% and 56% at 1, 2 and 5 years. The use of infliximab (p=0.006) and articular manifestations (p<0.05) were associated with treatment discontinuation. Considering cause of withdrawal, Ulcerative Colitis (UC) had a higher proportion of PNR (HR=4.99; 95% CI=1.71–14.63; p=0.003), SLR was higher if biologics had been indicated due to disease flare (HR=2.32; 95% CI=1.05–5.09; p=0.037) while AE were greater with infliximab (HR=2.46; 95% CI=1.48–4.08; p<0.001) or spondylitis (HR=2.46; 95% CI=1.78–6.89; p<0.001). According to the biological drug, HLA-DQA1*05 with adalimumab showed more SLR in cases with Crohn's disease (HR=3.49; 95% CI=1.39–8,78; p=0.008) or without concomitant immunomodulator (HR=2.8; 95% CI=1.1–6.93; p=0.026). ConclusionsHLA-DQ A1*05 was relevant in SLR of IBD patients treated with adalimumab without immunosupression. In patients treated with other biologics, clinical factors were more important for treatment interruption, mainly extensive UC or extraintestinal manifestations and having indicated the biologic for flare." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "IntroducciónEstudios previos han observado una asociación entre el HLA-DQA1*05 y la pérdida de respuesta a biológicos y el desarrollo de efectos adversos (EA). Hay factores clínicos y biológicos que podrían influir en la duración del tratamiento. El objetivo del estudio fue evaluar la influencia del HLA, de factores clínicos y terapéuticos en la interrupción del tratamiento biológico. MétodosSe realizó un estudio retrospectivo de pacientes con enfermedad inflamatoria intestinal (EII) tratados con biológicos entre 2007 y 2011. Los principales eventos analizados fueron la suspensión del tratamiento por fallo de respuesta primaria (PRP), secundaria (PRS) o EA. Se realizó un tipaje del HLA-DQA1*05 y se evaluaron los factores de riesgo de interrupción del tratamiento mediante un análisis de regresión logística. ResultadosSe incluyeron 150 pacientes y 312 tratamientos, de los cuales se suspendieron 147 (47%) en el seguimiento. El infliximab (p=0,006) y las manifestaciones articulares (p<0,05) se relacionaron con la interrupción del tratamiento. La colitis ulcerosa (CU) presentó mayor PRP (HR: 4,99; IC 95%: 1,71-14,63; p=0,003), el brote como indicación de tratamiento se asoció a más PRS (HR: 2,32; IC 95%: 1,05-5,09; p=0,037); el uso de infliximab (HR: 2,46; IC 95%: 1,48-4,08; p<0,001) y la espondilitis (HR: 2,46; IC 95%: 1,78-6,89; p<0,001) a la suspensión por EA. El HLA-DQA1*05 fue un factor de riesgo de PRS en los pacientes tratados con adalimumab (ADA) con enfermedad de Crohn (HR: 3,49; IC 95%: 1,39-8,78; p=0,008) o con EII sin inmunosupresor asociado (HR: 2,8; IC 95%: 1,1-6,93; p=0,026). ConclusionesEl HLA-DQA1*05 se asoció al cese del tratamiento con ADA por PRS en los pacientes con EII sin inmunosupresor asociado. Respecto a otros biológicos, la suspensión se debió más a factores como la CU, las manifestaciones articulares y la indicación para remisión de brote intestinal." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:3 [ "etiqueta" => "d" "nota" => "Co-first authors." "identificador" => "fn0005" ] ] "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:1 [ 0 => array:4 [ "apendice" => "The following are the supplementary data to this article:<elsevierMultimedia ident="upi0005"></elsevierMultimedia>" "etiqueta" => "Appendix A" "titulo" => "Supplementary data" "identificador" => "sec0105" ] ] ] ] "multimedia" => array:6 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1979 "Ancho" => 2508 "Tamanyo" => 237632 ] ] "descripcion" => array:1 [ "en" => "Flowchart of study population." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1934 "Ancho" => 1675 "Tamanyo" => 179084 ] ] "descripcion" => array:1 [ "en" => "(A) Secondary loss of response in IBD patients treated with adalimumab without immune-modulator. (B) Secondary loss of response in CD patients treated with adalimumab." ] ] 2 => 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:2 [ "leyenda" => "Abbreviations: EIMs, extraintestinal manifestations; IMM, immune-modulator." "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-with-role" title="\n \t\t\t\t\ttable-head\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Variables \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="6" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Total treatments (n=312)</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Discontinuation (n=147) \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">No discontinuation (n=165) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Univariable</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Multivariable</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">OR (95% CI) \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">p-Value \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">OR (95% CI) \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">p-Value \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="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Type of disease</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">Crohn's disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">99 (67) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">120 (73) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ulcerative 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">48 (33) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">45 (27) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.773 (0.5–1.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.300 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td-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">HLA DQ A1*05, 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">63 (43) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">60 (36) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.313 (0.8–2.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.241 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.331 (0.8–2.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.263 \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">Both alleles HLA DQ A1*05, 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">26 (18) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18 (11) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.755 (0.9–3.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.086 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td-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">EIMs, 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">95 (65) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">94 (57) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.380 (0.9–2.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.167 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Peripheral arthropathy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">63 (43) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">52 (32) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.630 (1.03–2.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.038 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.677 (1.02–2.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.039 \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">Spondylitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">19 (13) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.750 (1.7–13.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.085 (1.4–11.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.009 \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">Sacroilitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16 (11) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.916 (1.6–15.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.002 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.062 (1.5–16.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.007 \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">Cutaneous \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">33 (22) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">28 (17) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.416 (0.8–2.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.223 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Stomatitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24 (16) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">26 (16) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.043 (0.6–1.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.891 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ophthalmic \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 (4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.826 (0.7–4.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.220 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cholangitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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><td class="td" title="\n \t\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><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Thrombosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14 (10) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.825 (0.8–4.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.170 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td-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">Disease duration (yr), 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">10 (38) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14 (47) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.003 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Indication of treatment, n (%)</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Disease flare \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">123 (84) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">131 (79) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.330 (0.7–2.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.332 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Maintenance of remission \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14 (9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.539 (0.2–1.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.190 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Extraintestinal manifestations \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 (5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.744 (0.7–4.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.233 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Prevention of recurrence \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 (4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.631 (0.2–2.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.467 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Perianal disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1(1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.219 (0.03–1.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.219 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td-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">AntiTNF exposure, 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">126 (86) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">120 (73) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.250 (1.3–4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.005 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Naive, 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">64 (44) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">68 (41) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.100 (0.7–1.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.678 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Concomitant IMM, 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">57 (39) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">60 (36) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.108 (0.7–1.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.660 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Biologic exposure, n (%)</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" 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">73 (50) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">61 (37) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.682 (1.1–2.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.024 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.960 (1.2–3.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.006 \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 " align="char" 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">53 (36) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">59 (36) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.013 (0.6–1.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.956 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" 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">10 (7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16 (10) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.680 (0.3–1.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.356 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" 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">11 (8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">29 (18) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.379 (0.2–0.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.008 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3316854.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Risk factors for treatment discontinuation." ] ] 3 => 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:2 [ "leyenda" => "Abbreviations: EIMS, extraintestinal manifestations; IMM, immune-modulator." "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-with-role" title="\n \t\t\t\t\ttable-head\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Variables \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="6" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Crohn's disease (n=219)</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Discontinuation (n=99) \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">No discontinuation (n=120) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Univariable</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Multivariable</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">OR (95% CI) \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">p-Value \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">OR (95% CI) \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">p-Value \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HLA DQ A1*05, 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">51 (52) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">44 (37) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.835 (1.1–3.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.027 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.392 (0.9–2.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.141 \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">Both alleles HLA DQ A1*05, 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">19 (19) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (10) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.138 (1.0–4.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.052 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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">L1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">21 (18) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.414 (0.2–1.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.041 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">L2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 (9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.639 (0.2–1.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.393 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">L3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">63 (64) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">68 (57) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.338 (0.8–2.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.295 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">L4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22 (22) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20 (17) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.429 (0.7–2.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.299 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Behavior, 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">B1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">33 (33) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">43 (36) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.895 (0.5–1.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.699 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">B2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">77 (78) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">89 (74) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.219 (0.7–2.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.535 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">B3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">59 (60) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">58 (48) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.577 (0.9–2.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.096 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td-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">EIMs, 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">66 (67) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">67 (56) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.582 (0.9–2.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.102 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Peripheral arthropathy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (47) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">39 (33) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.803 (1.0–3.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.035 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.463 (1.0–2.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.072 \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">Spondylitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14 (14) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">19.600 (2.5–151.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.707 (1.9–7.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \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">Sacroilitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (10) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.258 (1.0–10.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.042 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.059 (1.4–6.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.003 \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">Cutaneous \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">31 (31) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22 (18) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.031 (1.1–3.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.026 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.168 (0.1–1.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.544 \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">Stomatitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 (15) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18 (15) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.012 (0.5–2.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.975 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ophthalmic \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (11) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.018 (0.8–5.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.157 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cholangitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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><td class="td" title="\n \t\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><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td></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">Thrombosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13 (13) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.116 (0.8–5.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.106 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td-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">Perianal disease, 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">48 (49) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">62 (52) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.880 (0.5–1.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.639 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Indication of treatment, n (%)</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Disease flare \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">82 (83) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">90 (75) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.608 (0.8–3.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.160 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Maintenance of remission \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13 (11) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.347 (0.1–1.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.062 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Extraintestinal manifestations \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.022 (0.6–6.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.222 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Prevention of recurrence \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 (6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.680 (0.2–2.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.758 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Perianal disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.235 (0.02–2.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.225 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td-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">Harvey-Bradshaw Index, 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">5 (4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.166 (1.0–1.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.007 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Calprotectin (μg/g), median (IRQ) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">289 (1072) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">250 (1171) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.000 (1.0–1.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.685 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SESCD, median (IRQ) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 (8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.013 (0.9–1.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.515 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Rutgeerts score, 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">4 (2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.468 (0.9–2.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.053 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">AntiTNF exposure, 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">83 (84) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">89 (74) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.807 (0.9–3.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.083 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Naive, 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">40 (40) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">50 (42) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.949 (0.6–1.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.850 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Concomitant IMM, 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">39 (39) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">38 (32) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.403 (0.8–2.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.233 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Biologic exposure, 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">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">49 (50) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">40 (33) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.960 (1.1–3.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.015 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.671 (1.1–2.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.014 \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">34 (34) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">49 (41) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.758 (0.4–1.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.324 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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">6 (6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 (3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.871 (0.5–6.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.353 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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">10 (10) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">27 (23) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.387 (0.2–0.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.015 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3316853.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Risk factors for treatment discontinuation in CD patients." ] ] 4 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "Abbreviations: EIMs, extraintestinal manifestations; IMM, immune-modulator." "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-with-role" title="\n \t\t\t\t\ttable-head\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Variables \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="4" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Ulcerative colitis (n=93)</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Discontinuation (n=48) \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">No discontinuation (n=45) \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">OR (95% CI) \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">p-Value \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HLA DQ A1*05, 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">12 (25) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16 (36) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.604 (0.2–1.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.267 \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">Both alleles HLA DQ A1*05, 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">7 (15) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 (13) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.110 (0.3–3.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.862 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Extension, 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">E1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.933 (0.3–29.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.618 \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">E2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (19) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 (13) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.500 (0.5–4.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.478 \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">E3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">38 (79) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">38 (84) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.700 (0.2–2.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.510 \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="5" 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">EIMs, 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">29 (60) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">27 (60) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.018 (0.4–2.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.967 \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">Peripheral arthropathy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17 (35) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13 (29) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.350 (0.6–3.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.501 \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">Spondylitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (10) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 (9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.192 (0.3–4.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.000 \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">Sacroilitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 (13) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.143 (1.0–1.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.027 \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">Cutaneous \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 (13) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.283 (0.05–1.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.150 \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">Stomatitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (19) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (18) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.067 (0.4–3.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.904 \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">Ophthalmic \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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><td class="td" title="\n \t\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><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cholangitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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><td class="td" title="\n \t\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><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Thrombosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1(2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.936 (0.06–15.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.000 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Indication of treatment, n (%)</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Disease flare \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">41 (85) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">41 (91) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.571 (0.2–2.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.395 \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">Maintenance of remission \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.933 (0.3–29.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.618 \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">Extraintestinal manifestations \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.273 (0.3–6.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.000 \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">Prevention of recurrence \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">—- \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Perianal disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">—- \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">— \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></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, mean (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (–) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.697 (0.9–3.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.118 \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">Calprotectin (μg/g), median (IRQ) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">591 (1209) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">158 (1768) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.000 (1.0–1.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.714 \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">Mayo endoscopic score, 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">1 (–) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.155 (0.5–2.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.748 \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">AntiTNF exposure, 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">43 (90) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">31 (69) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.884 (1.3–11.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.013 \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">Naive, 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">24 (50) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18 (40) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.500 (0.7–3.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.333 \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">Concomitant IMM, 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">18 (38) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22 (49) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.627 (0.3–1.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.268 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Biologic exposure, 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">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">24 (50) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">21 (47) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.143 (0.5–2.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.748 \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">19 (40) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (22) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.293 (0.9–5.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.071 \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">4 (8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 (27) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.250 (0.07–0.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.019 \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 (2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.457 (0.04–5.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.609 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3316852.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Risk factors for treatment discontinuation in UC." ] ] 5 => array:5 [ "identificador" => "upi0005" "tipo" => "MULTIMEDIAECOMPONENTE" "mostrarFloat" => false "mostrarDisplay" => true "Ecomponente" => array:2 [ "fichero" => "mmc1.doc" "ficheroTamanyo" => 27045 ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:31 [ 0 => array:3 [ "identificador" => "bib0160" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Enfermedad inflamatoria intestinal. 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Biological treatment interruption in inflammatory bowel disease: Motivation and predictive factors

Interrupción del tratamiento biológico en la enfermedad inflamatoria intestinal: causas y factores predictores

María Rocío Davis Gonzáleza,d, María Pilar Ballestera,b,d,

Corresponding author

mapibafe@gmail.com

Corresponding author.

, Eva Romero-Gonzáleza, Ana María Sánchez-Pardoa, David Marti-Aguadoa, Joan Toscaa, Carles Suriaa, Rosario Antón Ausejoa, Isabel Pascual Morenoa, María Dolores Planelles Silvestrec, Miguel Mínguez Péreza, Marta Maia Bosca-Wattsa

a IBD Unit, Digestive Disease Medicine, University of Valencia, University Clinic Hospital of Valencia, Spain

b Instituto de Investigación Sanitaria INCLIVA, Spain

c Histocompatibility Laboratory, Transfusion Center of Valencian Community, Valencia, Spain

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          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">&#40;A&#41; Secondary loss of response in IBD patients treated with adalimumab without immune-modulator&#46; &#40;B&#41; Secondary loss of response in CD patients treated with adalimumab&#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">IBD is a chronic disease whose treatment is sometimes complex because there is no established marker to indicate which treatments will work better on each patient&#46; In the past years&#44; studies have been performed to determine response-related factors&#44; with recent interest in genetic predisposition to explain loss of response&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">1</span></a> Development of antiTNF-&#945; antibodies &#40;immunogenicity&#41; has been related to the loss-of-response to antiTNF drugs and to the development of side effects&#46;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">2&#8211;5</span></a> Based on this&#44; some authors link response to biologics and tolerance to having the HLA-DQ A1&#42;05 allele&#44; and have therefore proposed determining this allele to decide what to prescribe&#46;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">2&#44;3&#44;5</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Besides genetics&#44; other factors such as the amount of inflammation may influence response to biologic treatment and&#44; therefore&#44; treatment duration&#46; This depends on disease extension&#44;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">6</span></a> flare severity&#44;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">1</span></a> having perianal disease<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">7</span></a> or extraintestinal symptoms&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">1</span></a> The type of biologic that is used<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">8</span></a> and co-treatments<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">9&#44;10</span></a> also play an important role in therapeutic response&#44; as well as side effects that may lead to treatment interruption&#46; Nevertheless&#44; the interaction of genetic&#44; clinical and therapeutic factors on the risk of treatment interruption has not been widely studied&#44; and even less with the most recent biological drugs&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Our hypothesis was that biological treatment discontinuation depends not only on HLA-DQA1&#42;05&#44; but also&#44; and more importantly&#44; on clinical and therapeutic factors in real-life-practice&#46; Our objective was to evaluate the influence of clinical and therapeutic factors&#44; along with HLA&#44; in biological treatment discontinuation&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Materials and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Study design and patient population</span><p id="par0020" class="elsevierStylePara elsevierViewall">An observational&#44; retrospective with prospectively gathered data&#44; single-center&#44; cohort study was performed&#46; All consecutive patients with IBD diagnosis&#44; followed in the IBD Unit of the Clinic University Hospital of Valencia&#44; Spain&#44; from 2007 until 2011 were screened for eligibility&#46; Inclusion criteria were&#58; firm IBD diagnosis&#44; age &#62;18 years and&#44; at least&#44; a single exposure to biological drugs &#40;infliximab -IFX-&#44; adalimumab -ADA-&#44; vedolizumab -VDZ- or ustekinumab -USTE-&#41;&#46; Patients with irregular follow-up or non-adherent according to medical criteria&#44; were excluded&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Data collection and follow-up</span><p id="par0025" class="elsevierStylePara elsevierViewall">Data were collected from our single-center ENEIDA registry&#46; The ENEIDA Registry is a prospectively maintained database of IBD patients of the Spanish Crohn&#39;s and Colitis Work Group &#40;GETECCU&#41;&#44; initiated in 2006&#46; This registry includes demographic&#44; clinical&#44; endoscopic and therapeutic data&#46; Patients were followed from date of diagnosis until date of death&#44; last visit or study closure in December 2020&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Variables included when biological drug initiation were&#58; age&#44; sex&#44; IBD type&#44; phenotypic expression of the disease&#44; extraintestinal manifestations&#44; complications&#44; type of biological treatment&#44; previous biological treatments &#40;or na&#239;ve&#41;&#44; concomitant immune-modulators and disease duration&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Treatment discontinuation as the main outcome was recorded at any time during follow-up&#44; including motivation for withdrawal and duration of treatment&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Definitions</span><p id="par0040" class="elsevierStylePara elsevierViewall">Diagnosis of IBD was made by local gastroenterologists based on standard clinical&#44; endoscopic&#44; and pathological criteria according to the European Crohn&#39;s and Colitis Organization &#40;ECCO&#41; consensus guidelines&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">11</span></a> Disease extent was determined with ileocolonoscopy and classified according to the Montreal classification&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">12</span></a> The maximum extent of disease at any time since diagnosis until biological treatment initiation was assigned for each patient&#46; The extraintestinal manifestations taken into account were peripheral arthropathy&#44; ankylosing spondylitis&#44; sacroilitis&#44; cutaneous &#40;erythema nodosum or pyoderma gangrenosum&#41;&#44; aphthous stomatitis&#44; ophthalmic &#40;iritis or episcleritis&#41;&#44; primary sclerosing cholangitis and thrombosis&#46; Complications considered were megacolon&#44; major acute hemorrhage defined as hematochezia or melena with hemodynamic instability &#40;hypotension or orthostatic change in vital signs&#41; and&#47;or an acute decrease in hemoglobin concentration of at least 2<span class="elsevierStyleHsp" style=""></span>mg&#47;dL compared with baseline&#44; bowel perforation or intra-abdominal abscesses&#46; Irregular follow-up was considered when the patient did not attend two consecutive appointments&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Biological treatment regimen for IBD was the same in all patients&#44; based on Spanish-developed guidelines&#44; which is in agreement with ECCO guidelines&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">13&#44;14</span></a> Patients were regularly monitored at the IBD Unit and intensification of treatment was performed taking into account both symptoms and drug levels&#46; Medication exposure was defined as the administration of&#44; at least&#44; one dose of an IBD-related drug&#46; Disease activity at the time of biological drug initiation was assessed based on the Harvey&#8211;Bradshaw index<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">15</span></a> or partial Mayo score&#44;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">16</span></a> calprotectin levels and&#47;or endoscopy activity evaluated with endoscopic SESCD&#44;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">17</span></a> Mayo score<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">16</span></a> or Rutgeerts<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">18</span></a> when available&#46; Treatment discontinuation included the interruption of medication due to primary non-response &#40;PNR&#41;&#44; secondary loss of response &#40;SLR&#41; or adverse events &#40;AE&#41;&#46; PNR was considered when lack of response during the first 16 weeks after initiation of biological drug&#44; despite intensification or modifications in concomitant drugs&#44; led to the suspension of treatment&#46; SLR was taken into account when the appearance of symptoms or intestinal inflammation assessed by an elevated calprotectin or activity on endoscopy&#44; led to the suspension of treatment throughout follow-up&#46; AE were categorized into immune-mediated &#40;infusion reactions&#44; flu-like syndrome&#44; chronic hypersensitivity and paradoxical reactions&#41;&#44; infections&#44; neoplasms&#44; hematological toxicity and others &#40;including those unspecific or not described but that had a temporary association with the drug and remitted when it was discontinued&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">19</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Genotypic analysis</span><p id="par0050" class="elsevierStylePara elsevierViewall">HLA-DQA1 low and high-resolution genotyping was performed by polymerase chain reaction with sequence-specific primers according to the method described by Olerup et al&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">20</span></a> Genomic DNA was isolated from nucleated cells by Magtration&#174; technology&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">21</span></a> Each PCR reaction was performed on about 80<span class="elsevierStyleHsp" style=""></span>ng of extracted DNA&#44; using 0&#46;15 units of Taq DNA polymerase &#40;AmpliTaq&#174; DNA Polymerase&#44; Applied Biosystems&#44; The Netherlands&#41;&#44; and Olerup commercial primers &#40;Olerup SSP AB&#44; Stockholm&#44; Sweden&#41;&#44; according to the manufacturer&#39;s instructions&#46; PCR was carried out in a final volume of 10<span class="elsevierStyleHsp" style=""></span>&#956;L in a GeneAmp PCR System 9700 &#40;Applied Biosystems&#44; The Netherlands&#41;&#46; An initial denaturizing step at 94<span class="elsevierStyleHsp" style=""></span>&#176;C for 2<span class="elsevierStyleHsp" style=""></span>min was followed by 10 two-temperature cycles &#40;94<span class="elsevierStyleHsp" style=""></span>&#176;C for 10<span class="elsevierStyleHsp" style=""></span>s and 65<span class="elsevierStyleHsp" style=""></span>&#176;C for 60<span class="elsevierStyleHsp" style=""></span>s&#41; and 20 three-temperature cycles &#40;94<span class="elsevierStyleHsp" style=""></span>&#176;C for 10<span class="elsevierStyleHsp" style=""></span>s&#44; 61<span class="elsevierStyleHsp" style=""></span>&#176;C for 50<span class="elsevierStyleHsp" style=""></span>s and 72<span class="elsevierStyleHsp" style=""></span>&#176;C for 30<span class="elsevierStyleHsp" style=""></span>s&#41;&#46; Detection of amplified alleles was carried out by agarose gel electrophoresis&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Statistical analysis</span><p id="par0055" class="elsevierStylePara elsevierViewall">Qualitative variables were expressed as frequencies &#40;&#37;&#41; and quantitative variables as mean and standard deviation &#40;SD&#41; or median and interquartile range &#40;IQR&#41;&#46; Univariate analysis was performed to compare genetic factors&#44; demographic variables&#44; phenotypic expression&#44; extraintestinal manifestations&#44; complications&#44; concomitant treatments and type of biological drugs with treatment discontinuation&#46; Comparison between groups was made using the <span class="elsevierStyleItalic">t</span>-test or Mann&#8211;Whitney U test for continuous data and the chi-square test or Fisher&#39;s test for categorical data&#44; as required&#46; Measures of association between qualitative variables were reported as odds ratio &#40;OR&#41; with 95&#37; confidence intervals &#40;95&#37; CI&#41;&#46; Time-to-treatment discontinuation was calculated with the Kaplan&#8211;Meier curve from the date of biological treatment initiation to the date of biological drug withdrawal&#44; death or study closure&#44; whichever came first&#46; Cox proportional hazard regression was used to evaluate the independent contribution of each factor on time-to-treatment interruption&#46; These results were expressed as hazard ratios &#40;HR&#41; with respective 95&#37; CI&#46; All statistical tests were two-sided&#46; A <span class="elsevierStyleItalic">p</span> value of &#60;0&#46;05 was considered statistically significant&#46; Covariates showing a clinical and statistical significance or participating as a confounding factor for the variable of interest were included in the multivariable models&#46; All analyses were performed with the SPSS V22&#46;0 software package&#46;</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Results</span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Study population</span><p id="par0060" class="elsevierStylePara elsevierViewall">We had determined HLA-DQ A1&#42;05 on 457 consecutive patients of which 150 were eligible because they were on biologics &#40;108 CD and 42 UC&#44; <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#58; 91 &#40;61&#37;&#41; males and 59 &#40;39&#37;&#41; females&#46; The median age at IBD diagnosis was 26 in CD patients and 28 in UC patients&#46; Mean follow-up from date of diagnosis was 21 &#40;SD 7&#41; years&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Patients characteristics according to HLA-DQA1&#42;05</span><p id="par0065" class="elsevierStylePara elsevierViewall">Prevalence of HLA-DQA1&#42;05 was 40&#37; &#40;95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>32&#8211;48&#41; in the total population &#40;14&#37; with two HLA DQ-A1&#42;05 alleles&#41;&#44; with a prevalence of 38&#37; &#40;95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>23&#8211;53&#41; in UC and 41&#37; &#40;95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>31&#8211;50&#41; in CD &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;766&#41;&#46; A higher proportion of extensive UC &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;8&#59; 95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;4&#8211;2&#46;5&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;033&#41; and a tendency to present more CD with perianal involvement &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;059&#41; were observed in cases with positive HLA-DQA1&#42;05 &#40;<a class="elsevierStyleCrossRef" href="#sec0105">Supplementary Table 1</a>&#41;&#46; There were no significant differences in follow-up between patients with or without positive HLA-DQA1&#42;05 &#40;22<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8 vs&#46; 20<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;073&#41;&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Biological regimens</span><p id="par0070" class="elsevierStylePara elsevierViewall">A total of 312 biological treatments were administered &#40;219 in CD and 93 in UC&#41; during follow-up&#46; Median number of biological drugs received by patient was 2 &#40;IQR 1&#8211;3&#41;&#44; in both CD and UC patients&#46; A higher proportion of na&#239;ve patients received IFX with respect to non-na&#239;ve &#40;63&#37; vs&#46; 29&#37;&#59; OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#46;170&#59; 95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#46;6&#8211;6&#46;7&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; while more non-na&#239;ve patients were treated with ADA &#40;41&#37; vs&#46; 30&#37;&#59; OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;615&#59; 95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;381&#8211;0&#46;991&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;045&#41;&#44; VDZ &#40;13&#37; vs&#46; 2&#37;&#59; OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;100&#59; 95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;023&#8211;0&#46;431&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; or USTE &#40;18&#37; vs&#46; 6&#37;&#59; OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;298&#59; 95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;133&#8211;0&#46;671&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;002&#41;&#44; both in CD and UC&#46; Similarly&#44; associated immune-modulator &#40;IMM&#41; treatment was more frequent in patients that received IFX &#40;51&#37; vs&#46; 39&#37;&#59; OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;684&#59; 95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;060&#8211;2&#46;677&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;027&#41; while no significant differences were observed with ADA &#40;33&#37; vs&#46; 38&#37;&#59; OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;787&#59; 95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;485&#8211;1&#46;275&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;333&#41;&#44; VDZ &#40;8&#37; vs&#46; 9&#37;&#59; OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;873&#59; 95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;376&#8211;2&#46;026&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;751&#41; or USTE &#40;9&#37; vs&#46; 15&#37;&#59; OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;594&#59; 95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;285&#8211;1&#46;240&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;162&#41;&#46; The main indication for a biological drug was disease flare&#44; and this group of patients had a significantly higher probability of receiving IFX &#40;89&#37; vs&#46; 76&#37;&#59; OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#46;567&#59; 95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;357&#8211;4&#46;855&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;003&#41; and lower of ADA &#40;72&#37; vs&#46; 87&#37;&#59; OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;408&#59; 95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;228&#8211;0&#46;728&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;002&#41;&#46; Biological treatments according to genotypic analysis is described in <a class="elsevierStyleCrossRef" href="#sec0105">Supplementary Table 2</a>&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Motivation for biological treatment discontinuation</span><p id="par0075" class="elsevierStylePara elsevierViewall">Of the 312 biological drugs&#44; 147 &#40;47&#37;&#41; were discontinued during study follow-up&#46; The cumulative probability of treatment discontinuation was 30&#37;&#44; 41&#37; and 56&#37; at 1&#44; 2 and 5 years of biological treatment initiation&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">The reasons for treatment discontinuation were loss of response and AE in 79 &#40;25&#37;&#41; and 68 &#40;22&#37;&#41; of biologic treatment&#44; respectively&#44; without significant differences in patients with and without positive HLA-DQA1&#42;05 &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;241&#41;&#46; Mean time for biological treatment discontinuation was significantly lower in patients with SLR &#40;22 &#8211;95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>17&#8211;27 &#8211; vs&#46; 59 &#8211; 95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>50&#8211;68 &#8211; months&#59; log rank<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>22&#46;554&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; or AE &#40;23 &#8211; 95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>16&#8211;30 &#8211; vs&#46; 59 &#8211; 95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>50&#8211;68 &#8211; months&#59; log rank<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>42&#46;753&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Risk factors for treatment discontinuation</span><p id="par0085" class="elsevierStylePara elsevierViewall">Risk factors for treatment discontinuation are shown in <a class="elsevierStyleCrossRefs" href="#tbl0005">Tables 1&#8211;3</a>&#44; for all the cases&#44; patients with CD and patients with UC&#44; respectively&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">Anti-TNF therapy was associated with treatment discontinuation &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#46;250&#59; 95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;266&#8211;3&#46;999&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;005&#41;&#44; mainly with IFX &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;682&#59; 95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;070&#8211;2&#46;643&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;024&#41;&#46; Shorter disease duration at the time of biological treatment initiation was associated with higher treatment interruption &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;931&#59; 95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;903&#8211;0&#46;961&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; Some of the extraintestinal manifestations were also associated with biological drug discontinuation&#44; including peripheral arthropathy &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;630&#59; 95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;026&#8211;2&#46;590&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;038&#41;&#59; ankylosing spondylitis &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#46;750&#59; 95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;726&#8211;13&#46;070&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; or sacroilitis &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#46;916&#59; 95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;605&#8211;15&#46;062&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;002&#41;&#46; Multivariable analysis including significant factors of the univariable analyses and HLA-DQ A1&#42;05 kept IFX therapy&#44; disease duration and extraintestinal manifestations as significant factors of treatment discontinuation while HLA-DQA1&#42;05 did not show significant influence &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">In patients with CD&#44; HLA-DQA1&#42;05 positive had a higher risk of treatment discontinuation in univariable analyses &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;027&#41;&#46; Treatment discontinuation was also associated with IFX and several extraintestinal manifestations &#40;peripheral arthropathy&#44; ankylosing spondylitis&#44; sacroilitis and cutaneous manifestations&#41;&#46; Multivariable analysis kept IFX therapy&#44; spondylitis and sacroileitis as significant factors of treatment discontinuation&#44; but no HLA-DQ &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Cause and time-to-treatment interruption</span><p id="par0100" class="elsevierStylePara elsevierViewall">A higher proportion of PNR was seen in patients with UC than with CD &#40;HR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#46;998&#59; 95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;707&#8211;14&#46;629&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;003&#41;&#44; mainly associated with extensive colitis &#40;HR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#46;680&#59; 95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;334&#8211;10&#46;150&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;012&#41;&#46; Only disease flare as indication of biological treatment was associated to shorter time-to-discontinuation due to SLR &#40;HR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#46;315&#59; 95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;051&#8211;5&#46;099&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;037&#41; while HLA-DQA1&#42;05 did not show significant influence &#40;HR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;231&#59; 95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;757&#8211;2&#46;005&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;400&#41;&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">A higher risk of AE was observed in patients with two alleles of HLA-DQA1&#42;05 &#40;46&#37; vs&#46; 25&#37;&#59; OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#46;551&#59; 95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;325&#8211;4&#46;911&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;004&#41;&#44; spondylitis &#40;46&#37; vs&#46; 26&#37;&#59; OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#46;403&#59; 95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;032&#8211;5&#46;594&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;037&#41; or on anti-TNF therapy &#40;32&#37; vs&#46; 11&#37;&#59; OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#46;987&#59; 95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;742&#8211;9&#46;125&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; Among anti-TNF drugs&#44; mainly IFX was associated to AE &#40;37&#37; vs&#46; 21&#37;&#59; OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#46;197&#59; 95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;326&#8211;3&#46;639&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;002&#41;&#44; most commonly immune-mediated &#40;27&#37; vs&#46; 12&#37;&#59; OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#46;746&#59; 95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;516&#8211;4&#46;976&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; and specially the paradoxical ones &#40;14&#37; vs&#46; 5&#37;&#59; OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#46;368&#59; 95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;194&#8211;9&#46;506&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;028&#41;&#46; Time-to-discontinuation of biological treatment due to AE was shorter with IFX therapy &#40;HR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#46;459&#59; 95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;482&#8211;4&#46;080&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; or spondylitis &#40;49 vs&#46; 112 months&#59; HR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#46;459&#59; 95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;778&#8211;6&#46;896&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; while two alleles of HLA-DQA1&#42;05 did not show significant influence &#40;HR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;619&#59; 95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;904&#8211;2&#46;898&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;105&#41; in the multivariable cox-proportional analyses&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Treatment discontinuation according to the biological regimen</span><p id="par0110" class="elsevierStylePara elsevierViewall">Focusing on ADA treatment&#44; cases with HLA-DQA1&#42;05 showed shorter time-to-treatment withdrawal due to SLR &#40;HR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#46;255&#59; 95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;070&#8211;4&#46;754&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;033&#41;&#46; This influence of HLA-DQA1&#42;05 on time-to discontinuation of ADA therapy was only seen in patients without concomitant IMM treatment &#40;HR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#46;803&#59; 95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;134&#8211;6&#46;926&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;026&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>A&#41; or with CD &#40;HR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#46;492&#59; 95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;388&#8211;8&#46;783&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;008&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>B&#41; but it was not present in patients with IMM &#40;HR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;483&#59; 95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;397&#8211;5&#46;537&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;557&#41; or with UC &#40;HR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;781&#59; 95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;157&#8211;3&#46;895&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;763&#41;&#46; Multivariable cox proportional regression analyses maintained HLA-DQA1&#42;05 &#40;HR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#46;484&#59; 95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;171&#8211;5&#46;273&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;018&#41; and disease flare as indication for ADA &#40;HR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#46;728&#59; 95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;355&#8211;16&#46;502&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;015&#41; as independent predictors of SLR&#46; No significant influence of HLA-DQA1&#42;05 was seen with IFX &#40;HR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;855&#59; 95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;399&#8211;1&#46;885&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;698&#41;&#44; USTE &#40;HR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;001&#59; 95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;222&#8211;4&#46;507&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;999&#41; or VDZ &#40;HR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;591&#59; 95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;066&#8211;5&#46;291&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;638&#41; on time-to discontinuation due to SLR&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Discussion</span><p id="par0115" class="elsevierStylePara elsevierViewall">Treatment of IBD must be personalized&#46; In order to give or interrupt treatment&#44; several aspects must be regarded&#58; genetics&#44; type of IBD&#44; phenotype of disease&#44; extraintestinal manifestations&#44; indication of treatment and the inflammatory burden&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">1</span></a> About one third of the patients do not respond to AntiTNF-&#945; induction &#40;20&#8211;40&#37; of CD and 30&#8211;40&#37; UC patients&#41;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">22</span></a> and another third of the patients lose response during maintenance treatment &#40;CD shows an annual SLR to IFX of 13&#37;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">23</span></a> and of 20&#37; with ADA<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">24</span></a>&#41;&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Several studies have demonstrated that HLA-DQA1&#42;05 is related to the development of antibodies against antiTNF drugs and to the SLR to antiTNF&#44;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">2&#8211;5</span></a> which could be something to keep in mind when starting biologics&#46; In clinical practice&#44; being able to maintain treatment&#44; despite immunogenicity&#44; certain AE&#44; or a loss of response&#44; is a goal that can be solved with treatment modifications such as intensifications or adding IMM&#46; We are frequently treating young patients that will need to be on biologics &#40;intermittently or continuously&#41; all their life&#44; so maintenance is crucial&#44; which is why we decided to use treatment discontinuation as the main outcome of our study&#46; In concrete&#44; we focused our analysis on the &#8220;negative&#8221; reasons for stopping treatment &#40;loss of response or side effects&#41;&#44; not those that were based on interrupting due to remission or the patient&#39;s will to stop&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">In 2020&#44; Sazonovs et al&#46;&#44; published a study in which they had included 1240 CD na&#239;ve patients treated with IFX or ADA for a flare&#59; they demonstrated that having one allele of HLA-DQ A1&#42;05 conferred a double risk of developing anti-TNF antibodies&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">5</span></a> That same year&#44; Wilson et al&#46; published the results of a retrospective study of 262 CD patients treated with IFX in which they had evaluated the relationship between HLA-DQA1&#42;05 and developing anti-TNF antibodies&#46; 79&#37; of the people that had at least one HLA-DQA1&#42;05 allele developed anti-TNF antibodies&#44; with a significantly higher risk than patients without the allele&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">4</span></a> Rodriguez-Alonso et al&#46;&#44; carried out a retrospective study of 64 patients treated with IFX&#44; who had been controlled until SLR&#46; The multivariable analysis showed that having HLA-DQ A1&#42;05 was the only factor associated to SLR&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">2</span></a> In two retrospective studies with small samples of patients &#40;53 and 20 patients&#41;&#44; the same group observed that HLA-DQ A1&#42;05 was only significant in SLR of patients on ADA&#44;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">3</span></a> and not on USTE&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">25</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">In our study&#44; we observed that HLA-DQ A1&#42;05 was related to a more frequent and earlier treatment withdrawal due to SLR in CD patients on ADA without IMM&#46; Patients with combotherapy of ADA and IMM did not show this difference&#44; probably due to a reduction in immunogenicity&#44; as the mentioned studies suggested&#46; Similar to studies such as Camps et al&#46;&#8217;s&#44;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">3</span></a> we observed the effect of this allele only in CD patients&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">We also looked into the relationship of HLA and clinical factors&#46; Extensive colitis has a higher inflammatory burden and is related to an increased risk of colectomy due to biological treatment failure&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">6</span></a> In agreement with previous results&#44; we observed that extensive colitis was significantly associated with treatment interruption due to PNR&#46; Similarly&#44; indicating biologics for a flare of the disease was significantly associated with SLR&#44; probably associated with more activity than when treatment is prescribed for remission maintenance or to prevent postoperative recurrence&#46; At the same time&#44; all of the UC patients that had at least one HLA-DQ A1&#42;05 allele had extensive colitis and a statistically significant higher Mayo score &#40;<a class="elsevierStyleCrossRef" href="#sec0105">Supplementary Tables 1 and 2</a>&#41;&#44; suggesting that in UC population&#44; HLA-DQ A1&#42;05 may be associated with more active and extensive colitis&#44; which was recently also observed in Nowak&#39;s pediatric population&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">26</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">With respect to the number of treatments the patient has received in relation to loss of response&#44; ADA has previously demonstrated efficacy and safety in UC and CD na&#239;ve and not-na&#239;ve to biologics&#44;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">8</span></a> although a considerably higher remission rate has been observed in patients who had not received IFX before being on ADA&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">27</span></a> We did not observe general differences in SLR according to being na&#239;ve or not&#46; The IFX group had a higher proportion of na&#239;ve patients&#44; whereas the ADA group had a similar distribution of na&#239;ve vs&#46; not na&#239;ve patients&#44; with an important number of patients who had failed with IFX &#40;generally SLR&#41;&#46; Since the ADA group is where we obtained a relationship between the HLA-DQA1&#42;05 and an increased SLR&#44; genetics might be more relevant in non-na&#239;ve patients to set a daily-practice habit of associating IMM in second-line anti-TNF who are HLA-DQA1&#42;05 positive&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">Several studies have observed fewer infusion reactions&#44; with less anti-IFX antibody formation&#44; combining IFX and azathioprine&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">10</span></a> Studies with ADA are less clear&#44; although a better response to induction treatment when combined with an IMM has been shown&#46;<a class="elsevierStyleCrossRefs" href="#bib0290"><span class="elsevierStyleSup">27&#44;28</span></a> When immunosuppression was analyzed with respect to PNR and SLR in both groups together &#40;IFX and ADA&#41;&#44; no differences were observed&#46; However&#44; a significantly earlier SLR was found in HLA-DQA1&#42;05 positive patients treated with ADA alone&#44; which was lost when an IMM was associated&#46; As we previously mentioned on na&#239;ve and non-na&#239;ve patients treated with ADA&#44; this might suggest that combotherapy with ADA and an IMM is probably especially useful in patients with this allele&#44; to avoid early SLR&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">The SUSTAIN study showed that loss of response with USTE was related to a high Harvey Bradshaw baseline index&#44; and unrelated to concomitant IMM&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">29</span></a> We had 40 patients who had been on USTE&#46; In line with what has been published&#44;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">25</span></a> we did not find any relationship between having HLA-DQA1&#42;05&#44; SLR and USTE&#44; regardless of them being na&#239;ve or not&#44; or being on concomitant IMM&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">Amiot et al&#46; demonstrated that one third of the patients treated with VDZ had SLR&#44; especially CD patients&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">30</span></a> We have not found any study addressing the relationship between HLA-DQA1&#42;05 and loss of response or AE&#46; We did not observe any relationship between this allele or any of the factors we studied with SLR&#46; However&#44; the sample was small &#40;26 patients&#41; and further research is needed to confirm that HLA-DQA1&#42;05 does not influence response to VDZ&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">Paradoxical reactions are more frequent with anti-TNF but also appear with other biologics&#46; The SUSTAIN trial reported AE in 25 &#40;7&#37;&#41; of the patients treated with USTE&#44; mainly arthralgia and infections&#44; with two cases of psoriasis&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">29</span></a> With respect to VDZ&#44; a cohort study published in 2018 described skin and joint reactions&#47;side effects&#44; which included 11 psoriasis&#46; Eight of the 14 that had cutaneous reactions&#44; had also presented them with anti-TNF-&#945;&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">31</span></a> In our study&#44; IFX and spondylitis were significantly associated with treatment interruption due to AE&#46; They were also related to the development of paradoxical reactions&#44; as well as having two HLA-DQA1&#42;05 alleles&#46; Our study is in accordance with what has been published&#44; because IFX is the most immunogenic of the biologics we have included&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">19</span></a> Spondylitis is an extraintestinal manifestation with considerable genetic background&#46; Up to 75&#37; of CD patients with spondylitis are HLA-B27 positive&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">1</span></a> Spondylitis is more frequent in colonic and perianal CD&#44; and the risk of presenting it increases with disease duration and inflammatory burden&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">1</span></a> Many mechanisms have been proposed to explain why spondylitis occurs in IBD&#46; One would be the appearance of antibodies and circulating immune complexes against common epitopes in different locations&#58; colon&#44; eyes&#44; skin&#44; joints and biliary epithelium&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">1</span></a> This has not been demonstrated&#44; but it would explain the association we found between spondylitis and paradoxical reactions&#44; because they would share the same mechanism of action&#46; Genetic predisposition &#40;mainly having two HLA-DQ A1&#42;05 alleles&#41; could be the basis of both mechanisms&#46; In our study&#44; CD patients with spondylitis had a tendency to carry one HLA-DQA1&#42;05 allele &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;059&#41;&#44; with a statistically significant difference if they had two HLA-DQ A1&#42;05 alleles &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;010&#41;&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">Our study has two main strong points that should be mentioned&#58; we studied not only CD but also UC patients in whom HLA-DQ A1&#42;05 has barely been analyzed&#44; and considered not only anti-TNF&#44; but also USTE and VDZ &#40;the latter which&#44; to our knowledge&#44; has not been analyzed yet&#41;&#46; These two points will probably be useful in clinical practice&#44; a part from the reinforcement of taking HLA-DQA1&#42;05 into account when prescribing ADA without IMM&#46; In addition&#44; we have studied treatments instead of patients so that we could correctly analyze first or second&#47;third-line treatments&#46; On the other hand&#44; the limitations of the study are that&#44; although data has been prospectively gathered&#44; the analysis is retrospective&#44; and that some of the subanalysis have a small sample size &#40;for example with VDZ&#41;&#46; Despite these limitations&#44; the results are relevant because there are few studies that directly contribute to personalize medicine using HLA-DQ&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">In conclusion&#44; according to our results&#44; HLA-DQA1&#42;05 is relevant in SLR of IBD patients treated with ADA without IMM&#46; In CD and UC patients treated with other biologics &#40;IFX&#44; USTE and VDZ&#41;&#44; clinical factors associated with higher inflammatory activity were more important for treatment interruption&#44; mainly extensive UC&#44; extraintestinal manifestations and having indicated the biologic for a flare&#46; Being on IFX&#44; having associated spondylitis and carrying two HLA-DQ A1&#42;05 alleles&#44; were related to the appearance of paradoxical reactions &#40;psoriasis&#44; arthritis&#44; suppurative hidradenitis and systemic erythematosus lupus&#41; that let to treatment interruption&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">Our results support some of the published data from other groups&#44; and offer a new point of view suggesting that a combination of genetic and clinical factors can guide our treatment decisions&#46; We would need prospective studies&#44; with bigger simple sizes&#44; to confirm our results&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Summary</span><p id="par0180" class="elsevierStylePara elsevierViewall">We present a retrospective study of Inflammatory Bowel Disease &#40;IBD&#41; patients&#46; Our aim was to evaluate the influence of HLA-DQ A1&#42;05&#44; along with other clinical and therapeutic factors&#44; in biological treatment discontinuation due to loss of response or adverse events&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Ethical considerations</span><p id="par0185" class="elsevierStylePara elsevierViewall">Informed consent to participate in our database was obtained from all patients&#46; The study was approved by the institutional ethics committee of the hospital on 2021&#46; The study complies with the principles of Good Clinical Practice and the Helsinki Declaration&#46;</p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Conflict of interest</span><p id="par0190" class="elsevierStylePara elsevierViewall">Mar&#237;a Roc&#237;o Davis Gonz&#225;lez declares educational activities sponsored by MSD&#44; Ferring&#44; Abbvie&#44; Janssen and Takeda&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">Maria Pilar Ballester is supported by a R&#237;o Hortega award &#40;<span class="elsevierStyleGrantNumber" refid="gs1">CM19&#47;00011</span>&#41;&#44; <span class="elsevierStyleGrantSponsor" id="gs1">Instituto de Salud Carlos III</span> &#40;Spanish Ministry of Science and innovation&#41;&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">Carles Suria declares educational activities and research projects sponsored by Ferring&#44; Abbvie&#44; Janssen and AztraZeneca&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">David Marti-Aguado is recipient of a R&#237;o Hortega award &#40;<span class="elsevierStyleGrantNumber" refid="gs1">CM19&#47;00212</span>&#41;&#44; Instituto de Salud Carlos III &#40;Spanish Ministry of Science and innovation&#41;&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">Miguel M&#237;nguez P&#233;rez has served as a speaker&#44; a consultant&#44; and advisory member for or has received research funding from <span class="elsevierStyleGrantSponsor" id="gs2">MSD</span>&#44; <span class="elsevierStyleGrantSponsor" id="gs3">Abbvie</span>&#44; <span class="elsevierStyleGrantSponsor" id="gs4">Pfizer</span>&#44; <span class="elsevierStyleGrantSponsor" id="gs5">Janssen</span>&#44; <span class="elsevierStyleGrantSponsor" id="gs6">Shire Pharmaceuticals</span>&#44; <span class="elsevierStyleGrantSponsor" id="gs7">Allergan</span>&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">Marta Maia Bosca-Watts declares educational activities&#44; research projects&#44; scientific meetings and advisory boards sponsored by MSD&#44; Ferring&#44; Abbvie&#44; Janssen&#44; Biogen and Takeda&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">The other authors declare no financial disclosures or conflicts of interest&#46;</p></span></span>"
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              "titulo" => "Cause and time-to-treatment interruption"
            ]
            6 => array:2 [
              "identificador" => "sec0075"
              "titulo" => "Treatment discontinuation according to the biological regimen"
            ]
          ]
        ]
        7 => array:2 [
          "identificador" => "sec0080"
          "titulo" => "Discussion"
        ]
        8 => array:2 [
          "identificador" => "sec0085"
          "titulo" => "Summary"
        ]
        9 => array:2 [
          "identificador" => "sec0090"
          "titulo" => "Ethical considerations"
        ]
        10 => array:2 [
          "identificador" => "sec0095"
          "titulo" => "Conflict of interest"
        ]
        11 => array:2 [
          "identificador" => "xack698220"
          "titulo" => "Acknowledgments"
        ]
        12 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2022-08-04"
    "fechaAceptado" => "2022-10-18"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1712427"
          "palabras" => array:5 [
            0 => "Inflammatory bowel disease"
            1 => "HLA-DQ A1&#42;05"
            2 => "Biological drugs"
            3 => "Secondary loss of response"
            4 => "Adverse events"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1712426"
          "palabras" => array:5 [
            0 => "Enfermedad inflamatoria intestinal"
            1 => "HLA-DQA1&#42;05"
            2 => "Biol&#243;gicos"
            3 => "P&#233;rdida secundaria de respuesta"
            4 => "Efectos adversos"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Loss-of-response and adverse events &#40;AE&#41; to biologics have been linked to HLA-DQA1&#42;05 allele&#46; However&#44; the clinical factors or biologic used may influence treatment duration&#46; Our objective was to evaluate the influence of clinical and therapeutic factors&#44; along with HLA&#44; in biological treatment discontinuation&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A retrospective study of consecutive IBD patients treated with biologics between 2007 and 2011 was performed&#46; Main outcome was treatment discontinuation due to primary non-response &#40;PNR&#41;&#44; secondary loss of response &#40;SLR&#41; or AE&#46; HLA-DQA1 genotyping was done in all patients&#46; Regression analyses were used to assess risk factors of treatment discontinuation&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">One hundred fifty patients &#40;61&#37; male&#41; with 312 biologic treatments were included&#46; 147 &#40;47&#37;&#41; were discontinued with a cumulative probability of 30&#37;&#44; 41&#37; and 56&#37; at 1&#44; 2 and 5 years&#46; The use of infliximab &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;006&#41; and articular manifestations &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41; were associated with treatment discontinuation&#46; Considering cause of withdrawal&#44; Ulcerative Colitis &#40;UC&#41; had a higher proportion of PNR &#40;HR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#46;99&#59; 95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;71&#8211;14&#46;63&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;003&#41;&#44; SLR was higher if biologics had been indicated due to disease flare &#40;HR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#46;32&#59; 95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;05&#8211;5&#46;09&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;037&#41; while AE were greater with infliximab &#40;HR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#46;46&#59; 95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;48&#8211;4&#46;08&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; or spondylitis &#40;HR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#46;46&#59; 95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;78&#8211;6&#46;89&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; According to the biological drug&#44; HLA-DQA1&#42;05 with adalimumab showed more SLR in cases with Crohn&#39;s disease &#40;HR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#46;49&#59; 95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;39&#8211;8&#44;78&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;008&#41; or without concomitant immunomodulator &#40;HR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#46;8&#59; 95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;1&#8211;6&#46;93&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;026&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">HLA-DQ A1&#42;05 was relevant in SLR of IBD patients treated with adalimumab without immunosupression&#46; In patients treated with other biologics&#44; clinical factors were more important for treatment interruption&#44; mainly extensive UC or extraintestinal manifestations and having indicated the biologic for flare&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Background"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Methods"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
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          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusions"
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      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Estudios previos han observado una asociaci&#243;n entre el&#160;HLA-DQA1&#42;05 y la p&#233;rdida de respuesta a biol&#243;gicos y el desarrollo de efectos adversos &#40;EA&#41;&#46; Hay factores cl&#237;nicos y biol&#243;gicos que podr&#237;an influir en la duraci&#243;n del tratamiento&#46; El objetivo del estudio fue evaluar la influencia del HLA&#44; de factores cl&#237;nicos y terap&#233;uticos en la interrupci&#243;n del tratamiento biol&#243;gico&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se realiz&#243; un estudio retrospectivo de pacientes con enfermedad inflamatoria intestinal &#40;EII&#41; tratados con biol&#243;gicos entre 2007 y 2011&#46; Los principales eventos analizados fueron la suspensi&#243;n del tratamiento por fallo de respuesta primaria &#40;PRP&#41;&#44; secundaria &#40;PRS&#41; o EA&#46; Se realiz&#243; un tipaje del HLA-DQA1&#42;05 y se evaluaron los factores de riesgo de interrupci&#243;n del tratamiento mediante un an&#225;lisis de regresi&#243;n log&#237;stica&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se incluyeron 150 pacientes y 312 tratamientos&#44; de los cuales se suspendieron 147 &#40;47&#37;&#41; en el seguimiento&#46; El infliximab &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;006&#41; y las manifestaciones articulares &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41; se relacionaron con la interrupci&#243;n del tratamiento&#46; La colitis ulcerosa &#40;CU&#41; present&#243; mayor PRP &#40;HR&#58; 4&#44;99&#59; IC 95&#37;&#58; 1&#44;71-14&#44;63&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;003&#41;&#44; el brote como indicaci&#243;n de tratamiento se asoci&#243; a m&#225;s PRS &#40;HR&#58; 2&#44;32&#59; IC 95&#37;&#58; 1&#44;05-5&#44;09&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;037&#41;&#59; el uso de infliximab &#40;HR&#58; 2&#44;46&#59; IC 95&#37;&#58; 1&#44;48-4&#44;08&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; y la espondilitis &#40;HR&#58; 2&#44;46&#59; IC 95&#37;&#58; 1&#44;78-6&#44;89&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; a la suspensi&#243;n por EA&#46; El HLA-DQA1&#42;05 fue un factor de riesgo de PRS en los pacientes tratados con adalimumab &#40;ADA&#41; con enfermedad de Crohn &#40;HR&#58; 3&#44;49&#59; IC 95&#37;&#58; 1&#44;39-8&#44;78&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;008&#41; o con EII sin inmunosupresor asociado &#40;HR&#58; 2&#44;8&#59; IC 95&#37;&#58; 1&#44;1-6&#44;93&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;026&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">El HLA-DQA1&#42;05 se asoci&#243; al cese del tratamiento con ADA por PRS en los pacientes con EII sin inmunosupresor asociado&#46; Respecto a otros biol&#243;gicos&#44; la suspensi&#243;n se debi&#243; m&#225;s a factores como la CU&#44; las manifestaciones articulares y la indicaci&#243;n para remisi&#243;n de brote intestinal&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Introducci&#243;n"
          ]
          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "M&#233;todos"
          ]
          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Resultados"
          ]
          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclusiones"
          ]
        ]
      ]
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      0 => array:3 [
        "etiqueta" => "d"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Co-first authors&#46;</p>"
        "identificador" => "fn0005"
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    "apendice" => array:1 [
      0 => array:1 [
        "seccion" => array:1 [
          0 => array:4 [
            "apendice" => "<p id="par0235" class="elsevierStylePara elsevierViewall">The following are the supplementary data to this article&#58;<elsevierMultimedia ident="upi0005"></elsevierMultimedia></p>"
            "etiqueta" => "Appendix A"
            "titulo" => "Supplementary data"
            "identificador" => "sec0105"
          ]
        ]
      ]
    ]
    "multimedia" => array:6 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1979
            "Ancho" => 2508
            "Tamanyo" => 237632
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Flowchart of study population&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Figure 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 1934
            "Ancho" => 1675
            "Tamanyo" => 179084
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">&#40;A&#41; Secondary loss of response in IBD patients treated with adalimumab without immune-modulator&#46; &#40;B&#41; Secondary loss of response in CD patients treated with adalimumab&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
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        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at1"
            "detalle" => "Table "
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>&#58; EIMs&#44; extraintestinal manifestations&#59; IMM&#44; immune-modulator&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Variables&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Total treatments &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>312&#41;</th></tr><tr title="table-row"><th class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">OR &#40;95&#37; CI&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span>-Value&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">OR &#40;95&#37; CI&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Type of disease</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Crohn&#39;s disease&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">99 &#40;67&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">120 &#40;73&#41;&nbsp;\t\t\t\t\t\t\n
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                  \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>Ulcerative colitis&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Peripheral arthropathy&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Spondylitis&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Sacroilitis&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Cutaneous&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#46;416 &#40;0&#46;8&#8211;2&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \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>Stomatitis&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;891&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Ophthalmic&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Cholangitis&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Thrombosis&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#46;825 &#40;0&#46;8&#8211;4&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \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
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                  \t\t\t\t"><span class="elsevierStyleItalic">Disease duration &#40;yr&#41;&#44; median &#40;IQR&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">10 &#40;38&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t  " colspan="7" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Indication of treatment&#44; n &#40;&#37;&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Disease flare&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">131 &#40;79&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#46;330 &#40;0&#46;7&#8211;2&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \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>Maintenance of remission&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">7 &#40;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">14 &#40;9&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;539 &#40;0&#46;2&#8211;1&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;190&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \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>Extraintestinal manifestations&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">12 &#40;8&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">8 &#40;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#46;744 &#40;0&#46;7&#8211;4&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;233&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#8212;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \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>Prevention of recurrence&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">4 &#40;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">7 &#40;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;631 &#40;0&#46;2&#8211;2&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;467&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \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>Perianal disease&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">1&#40;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">5 &#40;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;219 &#40;0&#46;03&#8211;1&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;219&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="7" align="left" valign="\n
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                  \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">AntiTNF exposure&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">126 &#40;86&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">120 &#40;73&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2&#46;250 &#40;1&#46;3&#8211;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">0&#46;005</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8212;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">68 &#40;41&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;100 &#40;0&#46;7&#8211;1&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8212;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Infliximab&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t  " align="char" 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
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Vedolizumab&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">0&#46;356&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Ustekinumab&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">0&#46;379 &#40;0&#46;2&#8211;0&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  """
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                  \t\t\t\t\tvoid\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t" scope="col">Variables&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col">Discontinuation &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>99&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col">No discontinuation &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>120&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Univariable</th><th class="td" title="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">OR &#40;95&#37; CI&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">OR &#40;95&#37; CI&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">HLA DQ A1&#42;05&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">0&#46;027&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Peripheral arthropathy&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#46;803 &#40;1&#46;0&#8211;3&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">0&#46;035</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#46;463 &#40;1&#46;0&#8211;2&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;072&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Spondylitis&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">&#60;0&#46;001</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">3&#46;707 &#40;1&#46;9&#8211;7&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">&#60;0&#46;001</span>&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Sacroilitis&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">10 &#40;10&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">4 &#40;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">3&#46;258 &#40;1&#46;0&#8211;10&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">0&#46;042</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">3&#46;059 &#40;1&#46;4&#8211;6&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">0&#46;003</span>&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>Cutaneous&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">31 &#40;31&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">22 &#40;18&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2&#46;031 &#40;1&#46;1&#8211;3&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">0&#46;026</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;544&nbsp;\t\t\t\t\t\t\n
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                  \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>Stomatitis&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">15 &#40;15&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">18 &#40;15&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#46;012 &#40;0&#46;5&#8211;2&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Ophthalmic&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;157&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Cholangitis&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Thrombosis&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">13 &#40;13&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">8 &#40;7&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2&#46;116 &#40;0&#46;8&#8211;5&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;106&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="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">Perianal disease&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">48 &#40;49&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">62 &#40;52&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;880 &#40;0&#46;5&#8211;1&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;639&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#8212;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#8212;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="7" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t  " colspan="7" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Indication of treatment&#44; n &#40;&#37;&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Disease flare&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">82 &#40;83&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">90 &#40;75&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Maintenance of remission&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">13 &#40;11&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;347 &#40;0&#46;1&#8211;1&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Extraintestinal manifestations&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#8212;&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
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                  \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>Prevention of recurrence&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">4 &#40;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">7 &#40;6&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;680 &#40;0&#46;2&#8211;2&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;758&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Perianal disease&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1 &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;225&nbsp;\t\t\t\t\t\t\n
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                  \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
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                  \t\t\t\t"><span class="elsevierStyleItalic">Harvey-Bradshaw Index&#44; median &#40;IQR&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">3 &#40;6&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#46;166 &#40;1&#46;0&#8211;1&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;007&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="elsevierStyleItalic">Calprotectin &#40;&#956;g&#47;g&#41;&#44; median &#40;IRQ&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">289 &#40;1072&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">250 &#40;1171&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#46;000 &#40;1&#46;0&#8211;1&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&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
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                  \t\t\t\t"><span class="elsevierStyleItalic">SESCD&#44; median &#40;IRQ&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">7 &#40;8&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">4 &#40;8&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#46;013 &#40;0&#46;9&#8211;1&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;515&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Rutgeerts score&#44; median &#40;IQR&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">4 &#40;2&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">3 &#40;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#46;468 &#40;0&#46;9&#8211;2&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">AntiTNF exposure&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">83 &#40;84&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">89 &#40;74&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Naive&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;850&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">&#8212;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Concomitant IMM&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Ustekinumab&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Peripheral arthropathy&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Spondylitis&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Sacroilitis&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Cutaneous&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Stomatitis&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Ophthalmic&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Cholangitis&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Thrombosis&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;936 &#40;0&#46;06&#8211;15&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Indication of treatment&#44; n &#40;&#37;&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \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>Disease flare&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;571 &#40;0&#46;2&#8211;2&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;395&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Maintenance of remission&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Extraintestinal manifestations&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Prevention of recurrence&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Perianal disease&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Partial Mayo score&#44; mean &#40;SD&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Calprotectin &#40;&#956;g&#47;g&#41;&#44; median &#40;IRQ&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">AntiTNF exposure&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Concomitant IMM&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Biologic exposure&#44; n &#40;&#37;&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Adalimumab&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Vedolizumab&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Ustekinumab&nbsp;\t\t\t\t\t\t\n
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Article information

ISSN: 02105705
Original language: English

DOI:10.1016/j.gastrohep.2022.10.021

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