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Background The long-term outcome of patients after antitumour necrosis factor alpha (anti-TNF) discontinuation is not well known. Aims To assess the risk of relapse in the long-term after anti-TNF discontinuation. Methods This was an extension of the evolution after anti-TNF discontinuation in patients with inflammatory bowel disease (EVODIS) study (Crohn's disease or ulcerative colitis patients treated with anti-TNFs in whom these drugs were withdrawn after achieving clinical remission) based in the same cohort of patients whose outcome was updated. Clinical remission was defined as a Harvey-Bradshaw index ≤4 points in Crohn's disease, a partial Mayo score ≤2 in ulcerative colitis and the absence of fistula drainage despite gentle finger compression in perianal disease. Results This was an observational, retrospective, multicenter study. A total of 1055 patients were included. The median follow-up time was 34 months. The incidence rate of relapse was 12% per patient-year (95% confidence interval [CI] = 11-14). The cumulative incidence of relapse was 50% (95% CI = 47-53): 19% at one year, 31% at 2 years, 38% at 3 years, 44% at 4 years and 48% at 5 years of follow-up. Of the 60% patients retreated with the same anti-TNF after relapse, 73% regained remission. Of the 75 patients who did not respond, 48% achieved remission with other therapies. Of the 190 patients who started other therapies after relapse, 62% achieved remission with the new treatment. Conclusions A significant proportion of patients who discontinued the anti-TNF remained in remission. In case of relapse, retreatment with the same anti-TNF was usually effective. Approximately half of the patients who did not respond after retreatment achieved remission with other therapies.

COVID-19; Immunosuppression; Inflammatory bowel disease COVID-19; Immunosupressió; Malaltia inflamatòria intestinal COVID-19; Inmunosupresión; Enfermedad inflamatoria intestinal (1) Scant information is available concerning the characteristics that may favour the acquisition of COVID-19 in patients with inflammatory bowel disease (IBD). Therefore, the aim of this study was to assess these differences between infected and noninfected patients with IBD. (2) This nationwide case−control study evaluated patients with inflammatory bowel disease with COVID-19 (cases) and without COVID-19 (controls) during the period March−July 2020 included in the ENEIDA of GETECCU. (3) A total of 496 cases and 964 controls from 73 Spanish centres were included. No differences were found in the basal characteristics between cases and controls. Cases had higher comorbidity Charlson scores (24% vs. 19%; p = 0.02) and occupational risk (28% vs. 10.5%; p < 0.0001) more frequently than did controls. Lockdown was the only protective measure against COVID-19 (50% vs. 70%; p < 0.0001). No differences were found in the use of systemic steroids, immunosuppressants or biologics between cases and controls. Cases were more often treated with 5-aminosalicylates (42% vs. 34%; p = 0.003). Having a moderate Charlson score (OR: 2.7; 95%CI: 1.3−5.9), occupational risk (OR: 2.9; 95%CI: 1.8−4.4) and the use of 5-aminosalicylates (OR: 1.7; 95%CI: 1.2−2.5) were factors for COVID-19. The strict lockdown was the only protective factor (OR: 0.1; 95%CI: 0.09−0.2). (4) Comorbidities and occupational exposure are the most relevant factors for COVID-19 in patients with IBD. The risk of COVID-19 seems not to be increased by immunosuppressants or biologics, with a potential effect of 5-aminosalicylates, which should be investigated further and interpreted with caution.

Background and Aims Clinical trials and real-life studies with ustekinumab in Crohn’s disease [CD] have revealed a good efficacy and safety profile. However, these data are scarcely available in elderly patients. Therefore, we aim to assess the effectiveness and safety of ustekinumab in elderly patients with CD. Methods Elderly patients [>60 years old] from the prospectively maintained ENEIDA registry treated with ustekinumab due to CD were included. Every patient was matched with two controls under 60 years of age, according to anti-tumour necrosis factor use and smoking habit. Values for the Harvey–Bradshaw Index [HBI], endoscopic activity, C-reactive protein [CRP] and faecal calprotectin [FC] were recorded at baseline and at weeks 16, 32 and 54. Results In total, 648 patients were included, 212 of whom were elderly. Effectiveness was similar between young and elderly patients during the follow-up. Steroid-free remission was similar at week 16 [54.6 vs 51.4%, p = 0.20], 32 [53.0% vs 54.5%, p = 0.26] and 54 [57.8% vs 51.1%, p = 0.21]. Persistence of ustekinumab as maintenance therapy was similar in both age groups [log-rank test; p = 0.91]. There was no difference in the rate of adverse effects [14.2% vs 11.2%, p = 0.350], including severe infections [7.1% vs 7.3%, p = 1.00], except for the occurrence of de novo neoplasms, which was higher in older patients [0.7% vs 4.3%, p = 0.003]. Conclusions Ustekinumab is as effective in elderly patients with CD as it is in non-elderly patients. The safety profile also seems to be similar except for a higher rate of de novo neoplasms, probably related to the age of the elderly patients.

Background: A recently registered device containing 80 mg of adalimumab (ADA) allows an alternative dose escalation regimen with ADA 80 mg every other week (EOW) given as a single subcutaneous injection instead of 40 mg every week. The ADASCAL study evaluated the preferences and satisfaction of inflammatory bowel disease (IBD) patients after switching their ADA regimen from 40 mg weekly to 80 mg EOW given with a single-dose pen. Methods: In this multicentre cross-sectional study, patients in whom the ADA regimen was changed from 40 mg weekly to 80 mg EOW completed the Treatment Satisfaction Questionnaire for Medication (TSQM 1.4), a four-item questionnaire [a Likert-type 5-point scale for preferences, two closed questions for convenience and a 100-point visual analogue scale (VAS) to assess which escalated ADA regimen patients would prefer to continue] and two Health-Related Quality of Life (HRQoL) questionnaires: the generic European Quality of Life–5 Dimensions (EQ-5D) and disease-specific Spanish version of the Inflammatory Bowel Disease Questionnaire (SIBDQ-9). Results: In total, 77 patients (64 Crohn’s disease and 13 ulcerative colitis) were included. The TSQM score showed a notably high global satisfaction [83.4, standard deviation (SD) = 14.1] of patients with ADA 80 mg EOW given with a single-dose pen, with high TSQM scores for individual components: effectiveness (77.6, SD = 16.9), convenience (83.7, SD = 14.5) and side effects (86.1, SD = 23.4). Most of the patients (74%) preferred the ADA EOW regimen (59.7% had strong preference, 14.3% slight preference). ADA EOW interferes less with daily activity (59.7%) and with travel plans (81.8%). Most patients (77%) would prefer to continue with ADA EOW (mean VAS score of 84.7, SD = 24.1, where 100 indicates a preference for ADA EOW). Patients reported high HRQoL scores on both the EQ-5D (72.3, SD = 20.1) and SIBDQ-9 (75.1, SD = 14.7). Conclusion: IBD patients in whom the ADA regimen was changed from 40 mg weekly to 80 mg EOW reported a higher preference for the EOW regimen and therefore most decided to continue with a single self-injection EOW.

Background and Aims The development programm UNIFI has shown promising results of ustekinumab in ulcerative colitis [UC] treatment which should be confirmed in clinical practice. We aimed to evaluate the durability, effectiveness, and safety of ustekinumab in UC in real life. Methods Patients included in the prospectively maintained ENEIDA registry, who received at least one intravenous dose of ustekinumab due to active UC [Partial Mayo Score [PMS]>2], were included. Clinical activity and effectiveness were defined based on PMS. Short-term response was assessed at Week 16. Results A total of 95 patients were included. At Week 16, 53% of patients had response [including 35% of patients in remission]. In the multivariate analysis, elevated serum C-reactive protein was the only variable significantly associated with lower likelihood of achieving remission. Remission was achieved in 39% and 33% of patients at Weeks 24 and 52, respectively; 36% of patients discontinued the treatment with ustekinumab during a median follow-up of 31 weeks. The probability of maintaining ustekinumab treatment was 87% at Week 16, 63% at Week 56, and 59% at Week 72; primary failure was the main reason for ustekinumab discontinuation. No variable was associated with risk of discontinuation. Three patients reported adverse events; one of them had a fatal severe SARS-CoV-2 infection. Conclusions Ustekinumab is effective in both the short and the long term in real life, even in a highly refractory cohort. Higher inflammatory burden at baseline correlated with lower probability of achieving remission. Safety was consistent with the known profile of ustekinumab.

Purpose: biosimilar infliximab (CTP-13) has been recently approved for the treatment of several immune-mediated inflammatory disorders, including inflammatory bowel disease (IBD). Comparative studies between this biosimilar and original infliximab in the real clinical practice are scarce. The objective of this study was to compare short and long-term safety and efficacy of original (O) and biosimilar infliximab (B-IFX) in biologic-naive, IBD patients in the real life clinical practice. Methods: a retrospective, multicentric study was performed in five Spanish hospitals. Consecutive IBD, biologic-naive patients from an historic cohort who initiated O-IFX from January 2013 were compared with biologic-naive patients, who started treatment with B-IFX since its approval in January 2015. The evaluation of efficacy was assessed after the induction phase, at week 14 and week 54 of treatment. Time to dose escalation or treatment persistence of both O-IFX and B-IFX was also considered. The appearance of serious adverse events was recorded. Results: two hundred and thirty-nine IBD biologic-naive patients who started with O-IFX or B-IFX were included: 153 patients were diagnosed with Crohn’s disease (95 treated with O- and 58 treated with B-IFX) and 86 with ulcerative colitis (40 received O- and 46 received B-IFX). At weeks 14 and 54, both O-IFX and B-IFX groups reached a similar clinical response and remission rates. Time to dose escalation, treatment persistence and safety profile were comparable between both groups. Conclusions: this long-term real-life experience provides additional evidence of the similarity of O- and B-IFX CTP-13 in terms of efficacy and safety in IBD patients.

ObjectiveTo estimate COVID-19 infection incidence rate with severe affectation (requiring hospitalization) in patients with biological treatment due to rheumatoid arthritis (RA), psoriatic arthritis (PsA), spondyloarthritis (SpA), psoriasis (Ps), and inflammatory bowel disease (IBD) and compare it with incidence rate in the general population.MethodsRetrospective observational study based on information provided by two administrative databases. One of these two databases contains information on all patients seen in our hospital and diagnosed with COVID-19 infection between March 4th 2020 and April 26th 2020. The other database contains data from patients seen at Rheumatology, Dermatology and Digestive Departments in our hospital who are currently receiving biological therapy. We calculated the crude and age and sex adjusted incidence in both groups. To compare both groups we calculated the Incidence Rate Ratio.ResultsThere was a total of 2,182 patients with COVID-19 requiring hospitalization. Four patients out of a total of 797 patients receiving biological therapy had contracted COVID-19 and required hospital care. Crude incidence rate of COVID-19 requiring hospital care among the general population was 1.41%, and it was 0.50% among the group receiving biological therapy. Rates adjusted by age and sex in the biological group was 0.45% (CI95% 0.11-4.13). The IRR of the group receiving biological therapy compared to the general population was 0.39 (CI95% 0.14-1, p=0.049).ConclusionFindings suggest that prior use of biological therapy does not associate with severe manifestations of COVID-19, and it is likely to have a protective effect against them when compared to the general population.Key MessagesWhat is already known about this subject?Covid-19 susceptibility in patients with immune-mediated disorders and receiving treatment with biological therapy is unknown.What does this study add?Severe manifestation incidence rate in patients with immune-mediated disorders receiving biological therapy treatment is not increased when compared to the general population.Biological therapies might protect patients from presenting severe COVID-19 manifestations.How might this impact on clinical practice?These data could be used for current recommendations regarding management of patients receiving biological therapies.Mini AbstractThe objective of this study is to analyze the incidence rate of severe COVID-19 requiring hospital care for patients receiving biological therapy and to compare it to the general population. Patients treated with biological therapy have crude and adjusted incidence rates under those of the general population.Statement of Human and Animal RightsThis article does not contain any studies involving human participants or animals that were performed by the authors. For this type of study, formal consent was therefore not required.

Background and Aims Although commonly used in inflammatory bowel disease [IBD], thiopurines frequently cause intolerance, and switching to a second thiopurine has only been reported in some small series. Ours aims in this study were to evaluate the safety of switching to a second thiopurine in a large cohort, and to assess the impact of age on tolerance. Methods Adult IBD patients from the ENEIDA registry, who were switched to a second thiopurine due to adverse events [excluding malignancies and infections], were identified. At the beginning of thiopurine treatment, patients were divided by age into two groups: 18–50 and over 60 years of age. The rate and concordance of adverse events between the first and second thiopurines, treatment intolerance, and persistence with the second thiopurine were evaluated. Results A total of 1278 patients [13% over 60 years of age] were switched to a second thiopurine. At 12 months, the cumulative probability of switch intolerance was 43%, and persistence with treatment was 49%. Independent risk factors of switch intolerance were age over 60 years (odds ratio [OR] 1.49; 95% confidence interval [CI] 1.07–2.07; p = 0.017) , previous gastrointestinal toxicity [OR 1.4; 95% CI 1.11–1.78; p = 0.005], previous acute pancreatitis [OR 6.78; 95% CI 2.55–18.05; p Conclusions In a large series in clinical practice, switching to a second thiopurine proved to be a valid strategy. Tight monitoring of elderly IBD patients switching to a second thiopurine because of adverse events is recommended.

Background Patients with inflammatory bowel disease (IBD) may present extraintestinal manifestations (EIMs) that affect the joints, skin, eyes, and hepatobiliary area, among others. Aims Our aim was to analyse the prevalence and characteristics of EIMs in patients with IBD and to identify the possible risk factors associated with the development of EIMs in the largest series published to date. Methods Observational, cross-sectional study including patients from the Spanish ENEIDA registry promoted by GETECCU. We retrospectively identified all cases of EIMs in the ENEIDA registry until January 2018. Results The study included 31,077 patients, 5779 of whom had at least one EIM (global prevalence 19%; 95% CI 18.2-19.0). Among the different types of EIMs, rheumatic manifestations had a prevalence of 13% (95% CI 12.9-13.7; 63% of EIMs), with a prevalence of 5% (95% CI 4.7-5.2) for mucocutaneous manifestations, 2.1% (95% CI 1.9-2.2) for ocular manifestations, and 0.7% (95% CI 0.6-0.8) for hepatobiliary manifestations. The multivariable analysis showed that the type of IBD (Crohn's disease,p < 0.001), gender (female,p < 0.001), the need for an immunomodulator (p < 0.001) or biologic drugs (p < 0.001), a previous family history of IBD (p < 0.001), and an extensive location of IBD (p < 0.001) were risk factors for the presence of EIMs. Conclusions One-fifth of patients with IBD may have associated EIMs, with rheumatic manifestations as the most frequent (> 60% of EIMs). Female patients with severe Crohn's disease represent the group with the highest risk of developing EIMs. These patients should therefore be specially monitored and referred to the corresponding specialist when suggestive symptoms appear.

Background The effectiveness of the switch to another anti–tumor necrosis factor (anti-TNF) agent is not known. The aim of this study was to analyze the effectiveness and safety of treatment with a second and third anti-TNF drug after intolerance to or failure of a previous anti-TNF agent in inflammatory bowel disease (IBD) patients. Methods We included patients diagnosed with IBD from the ENEIDA registry who received another anti-TNF after intolerance to or failure of a prior anti-TNF agent. Results A total of 1122 patients were included. In the short term, remission was achieved in 55% of the patients with the second anti-TNF. The incidence of loss of response was 19% per patient-year with the second anti-TNF. Combination therapy (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.8–3; P < 0.0001) and ulcerative colitis vs Crohn’s disease (HR, 1.6; 95% CI, 1.1–2.1; P = 0.005) were associated with a higher probability of loss of response. Fifteen percent of the patients had adverse events, and 10% had to discontinue the second anti-TNF. Of the 71 patients who received a third anti-TNF, 55% achieved remission. The incidence of loss of response was 22% per patient-year with a third anti-TNF. Adverse events occurred in 7 patients (11%), but only 1 stopped the drug. Conclusions Approximately half of the patients who received a second anti-TNF achieved remission; nevertheless, a significant proportion of them subsequently lost response. Combination therapy and type of IBD were associated with loss of response. Remission was achieved in almost 50% of patients who received a third anti-TNF; nevertheless, a significant proportion of them subsequently lost response.

Background and Aims Primary sclerosing cholangitis [PSC] is usually associated with inflammatory bowel disease [IBD]. An increased risk of malignancies, mainly colorectal cancer [CRC] and cholangiocarcinoma [CCA], has been reported in PSC-IBD patients. Our aim was to determine the clinical characteristics and management of PSC in IBD patients, and the factors associated with malignancies. Methods PSC-IBD patients were identified from the Spanish ENEIDA registry of GETECCU. Additional data were collected using the AEG-REDCap electronic data capture tool. Results In total, 277 PSC-IBD patients were included, with an incidence rate of 61 PSC cases per 100 000 IBD patient-years, 69.7% men, 67.5% ulcerative colitis and mean age at PSC diagnosis of 40 ± 16 years. Most patients [85.2%] were treated with ursodeoxycholic acid. Liver transplantation was required in 35 patients [12.6%] after 79 months (interquartile range [IQR] 50–139). It was more common in intra- and extrahepatic PSC compared with small-duct PSC (16.3% vs 3.3%; odds ratio [OR] 5.7: 95% confidence interval [CI] = 1.7–19.3). The incidence rate of CRC since PSC diagnosis was 3.3 cases per 1000 patient-years [95% CI = 1.9–5.6]. Having symptoms of PSC at PSC diagnosis was the only factor related to an increased risk of CRC after IBD diagnosis [hazard ratio= 3.3: 95% CI = 1.1–9.9]. CCA was detected in seven patients [2.5%] with intra- and extrahepatic PSC, with median age of 42 years [IQR 39–53], and presented a lower life expectancy compared with patients without CCA and patients with or without CRC. Conclusions PSC-IBD patients with symptoms of PSC at PSC diagnosis have an increased risk of CRC. CCA was only diagnosed in patients with intra- and extrahepatic PSC and was associated with poor survival.

Aim: To evaluate outcomes of early dose optimization of golimumab in ulcerative colitis (UC) patients with inadequate response to golimumab induction treatment.Methods: This observational, multicenter, cohort study included patients with moderate-to-severe active UC and with inadequate response to subcutaneous golimumab induction doses, in whom weight-based golimumab maintenance dose (European labeling) of 50mg every 4weeks (q4wk) was optimized before week 14 to 100mg q4wk. At week 14, we assessed clinical response and remission using the partial Mayo score. In the long term we evaluate the cumulative probabilities of golimumab failure-free survival and colectomy-free survival.Results: A total of 209 patients who received golimumab induction doses were eligible. Of these, 151 patients (72.2%) weighing less than 80kg were assigned to a golimumab maintenance dose of 50mg q4wk. Twenty-four patients (15.9% [12.5% overall]), in whom scheduled doses of 50mg q4wk were optimized to 100mg q4wk before week 14, compose the study population. At week 14, 16 patients (66.7%, 95% CI 45.7-87.6) had clinical response, of these 12 were corticosteroid free. Four patients (16.7%) achieved corticosteroid-free remission. After a median follow-up of 12months (IQR 10-22), 13 patients (54.2%) maintained clinical benefit. Thirteen of 16 patients (81.2%) with clinical response at week 14 maintained clinical benefit at last follow-up. All patients avoided colectomy. In none of the patients was golimumab dose de-escalated. There were no adverse events leading to golimumab withdrawal.Conclusion: Early optimization of golimumab dose induces clinical response at week 14 in two thirds of UC patients and leads to long-term clinical benefit in over half of patients.

Background Anti-TNF treatment is effective for Crohn's disease (CD); however, some patients did not achieve remission with these drugs. Aims To evaluate the short-term effectiveness of a second anti-TNF in CD patients who did not achieve remission with the first one and to assess its durability. Methods Patients who did not achieve remission with their first anti-TNF were included. The short-term response of the second anti-TNF was assessed, the long-term response was evaluated in patients who achieved remission (Kaplan–Meier). Cox-regression was performed to identify predictors of loss of efficacy. Results In all, 118 CD patients received a second anti-TNF after primary failure of the first. The first anti-TNF was discontinued because of non-response in 54% of patients and partial response in 46%. Fifty-one percent of patients achieved remission in the short-term. The probability of remission was lower in patients for whom the drug indication was perianal disease (OR = 0.3, 95% CI = 0.1–0.7, P = 0.005). The dose was increased in 33% of patients, and 37% achieved/regained remission. The probability of maintaining remission was 76%, 68% and 64% at 12, 18 and 24 months, respectively. Conclusions Approximately half of the patients achieved remission with a second anti-TNF after primary failure of the first, this strategy was less effective in patients with perianal disease.

Resumen Objetivo Describir la incidencia a los 2 anos de nuevas enfermedades inflamatorias mediadas por inmunidad (espondiloartritis, uveitis, psoriasis) en la cohorte de pacientes con enfermedad inflamatoria intestinal (EII) del estudio AQUILES. Material y metodos Durante un periodo de 2 anos se siguieron 341 pacientes con EII (53% mujeres, edad media 40 anos) diagnosticados de enfermedad de Crohn (60,5%), colitis ulcerosa (38,1%) y colitis indeterminada (1,4%). Los nuevos diagnosticos durante el seguimiento de los pacientes se basaron en los informes de los respectivos especialistas (reumatologos, oftalmologos y dermatologos). Resultados Se establecieron 22 nuevos diagnosticos de enfermedades inflamatorias mediadas por inmunidad en 21 pacientes (incidencia acumulada: 6,5% [intervalo de confianza del 95% —IC 95%—: 3,7-9,2], tasa de incidencia: 26 casos por 10.000 pacientes-ano). La mayoria de los diagnosticos fueron nuevos casos de espondiloartritis (n = 15). La incidencia acumulada de nuevos diagnosticos de enfermedades inflamatorias mediadas por inmunidad fue similar en pacientes con enfermedad de Crohn (5,8%, IC 95%: 3,4-9,9) y en pacientes con colitis ulcerosa (7,7%, IC 95%: 4,2-13,6). En el analisis multivariable la incidencia de nuevas enfermedades inflamatorias mediadas por inmunidad se asocio a historia familiar de EII ( odds ratio = 3,6, IC 95%: 1,4-9,4) y a la presencia de manifestaciones extraintestinales de EII ( odds ratio = 1,8, IC 95%: 0,7-5,2). Conclusiones En pacientes con EII la incidencia de nuevas enfermedades inflamatorias mediadas por inmunidad a los 2 anos de seguimiento fue del 6,5%, siendo mas frecuentes en pacientes con manifestaciones extraintestinales de EII e historia familiar de EII.

Substantial proportion of Crohn’s disease (CD) patients shows no response or a limited response to treatment with infliximab (IFX) and to identify biomarkers of response would be of great clinical and economic benefit. The expression profile of five genes (S100A8-S100A9, G0S2, TNFAIP6, andIL11) reportedly predicted response to IFX and we aimed at investigating their etiologic role through genetic association analysis. Patients with active CD (350) who received at least three induction doses of IFX were included and classified according to IFX response. A tagging strategy was used to select genetic polymorphisms that cover the variability present in the chromosomal regions encoding the identified genes with altered expression. Following genotyping, differences between responders and nonresponders to IFX were observed in haplotypes of the studied regions:S100A8-S100A9(rs11205276*G/rs3014866*C/rs724781*C/rs3006488*A;P=0.05);G0S2(rs4844486*A/rs1473683*T;P=0.15);TNFAIP6(rs11677200*C/rs2342910*A/rs3755480*G/rs10432475*A;P=0.10); andIL11(rs1126760*C/rs1042506*G;P=0.07). These differences were amplified in patients with colonic and ileocolonic location for all but theTNFAIP6haplotype, which evidenced significant difference in ileal CD patients. Our results support the role of the reported expression signature as predictive of anti-TNF outcome in CD patients and suggest an etiological role of those top-five genes in the IFX response pathway.

Resumen Objetivo Determinar la prevalencia de enfermedades inflamatorias mediadas por inmunidad (EIMI) en una cohorte de pacientes con enfermedad inflamatoria intestinal (EII) reclutada en consultas hospitalarias de aparato digestivo para el estudio Aquiles, un estudio prospectivo de 2 anos de seguimiento. Material y metodos Se incluyeron pacientes de ≥ 18 anos con diagnostico previo o nuevo de EII (enfermedad de Crohn [EC], colitis ulcerosa [CU] o colitis indeterminada). Los diagnosticos se recogieron de forma transversal de la historia clinica en el momento de incorporar a cada paciente al estudio. Resultados Se incluyeron 526 pacientes (edad media 40,2 anos; 47,3% hombres, 52,7% mujeres), 300 con EC (57,0%), 218 con CU (41,4%) y 8 colitis indeterminada. Presentaron otra EIMI 71 pacientes (prevalencia: 13,5%, IC 95%: 10,8-16,7): 47 fueron espondiloartritis (prevalencia: 8,9%); 18 psoriasis (3,4%); 5 pioderma gangrenoso (1,0%) y 11 uveitis (2,1%). La prevalencia de EIMI fue mayor en pacientes con EC respecto a pacientes con CU (17,0% [IC 95%: 13,2-21,7] frente a 9,2% [IC 95%: 6,0-13,8], p = 0,011). En el analisis multivariante, las variables asociadas a la presencia de EIMI fueron el diagnostico de EC (OR = 1,8 [IC 95%: 1,1-3,2]) y un tiempo de evolucion de la EII ≥ 4 anos (OR = 2,1 [IC 95%: 1,1-4,1] en aquellos con 4-8 anos, y OR = 2,1 [IC 95%: 1,2-3,9] en los de ≥ 8 anos frente a Conclusiones En la cohorte de pacientes con EII del estudio Aquiles, el 13,5% presento otra EIMI, con una prevalencia mayor en pacientes con EC y > 4 anos de evolucion de la enfermedad.

Beclometasone dipropionate (BDP) is a relatively new topically acting oral steroid to treat mild to moderately active ulcerative colitis (UC). We estimate that 20,000 patients have received oral BDP in Spain in the last two years. Our aim was to evaluate the efficacy and safety of oral BDP in clinical practice.Retrospective and multicenter study that included 434 patients with active UC treated with BDP. The partial Mayo Clinic score (pMS, 0-9) was used to measure disease activity. Remission was defined as post-treatment pMS of 0 or 1; response as a decrease in pMS of 3 points or 2 points and30%, and failure as lack of remission or response.BDP dose was 5 mg/day in 88% of patients and mean treatment duration was 6.2 weeks. BDP achieved remission in 44.4%, response in 22.3% and failed in 33.2% of patients. Mean pMS decreased from 4.9 ± 1.3 to 2.4 ± 2.3 (p0.0001). Remission rate was higher in mild and moderate than in severe UC (p0.043) and tended to be higher in left-sided and extensive UC than in proctitis (p0.06). Failure was less frequent in patients treated for4 weeks (p0.02). Mild adverse events were reported in 7.6% of patients.BDP induces response or remission in two thirds of active UC patients, with a good safety profile. Patients with mild to moderate, left-sided or extensive UC, receiving BDP for more than 4 weeks are most likely to benefit from this treatment.

Immunomodulators are used as maintenance treatment of inflammatory bowel disease (IBD). Data regarding their possible effects in the course of pregnancy when the father is exposed at the time of conception are limited.To evaluate the outcomes of pregnancies of which the fathers were exposed to thiopurines at the time of conception. A series of male patients followed in seven IBD clinics in Madrid, Spain, was studied. Any exposure to thiopurines during the 3 months preceding conception was considered significant. Controls were pregnancies fathered by patients who either had never been treated with thiopurines or had interrupted them3 months before conception. Statistical comparisons and multivariate analysis were carried out with the generalized estimating equations model.There were 46 conceptions in the exposed group (mercaptopurine 9, azathioprine 37) and 84 in the control group. In the exposed group, there were more Crohn's patients (82.6% vs. 53.6%), the duration of the disease was longer (median: 8 vs. 5 years), fathers were slightly older (mean: 34.2 vs. 32.7 years), and there were fewer patients on mesalamine (15.2% vs. 47.6%). Otherwise, baseline characteristics were similar in both groups. There were no significant differences regarding unsuccessful pregnancies-namely, spontaneous abortions, ectopic pregnancies, anembryonic pregnancies, or fetal deaths (10.9% exposed group vs. 13.1% control group; odds ratio (OR): 0.79, confidence interval (CI): 0.22-2.85), preterm births (4.3% vs. 2.4%; OR: 1.3, CI: 0.22-7.61), low birth weight (6.5% vs. 6%; OR: 1.06, CI: 0.25-4.54), or congenital malformations (2.2% vs. 2.4%; OR: 0.82, CI: 0.08-9). No infant neoplasms were detected. The proportion of conceptions that needed1 year to be achieved was higher in the exposed group, but this was not statistically significant (15.2% vs. 8.3%; OR: 1.92, CI: 0.54-6.88). Multivariate analysis was carried out for unsuccessful pregnancies and fertility impairment, and it showed that, although mesalamine exposure confounded the effect of the exposure to thiopurines on these outcomes, this effect was still nonsignificant (respectively, OR: 0.49, CI: 0.17-1.44; OR: 2.82, CI: 0.7-11.38).Our data do not support the practice of routinely recommending to male patients that they interrupt thiopurines when wanting to conceive.

Efficacy of infliximab in Crohn's disease (CD) showed by randomized controlled trials must be confirmed in clinical practice. We aimed to evaluate efficacy and safety of infliximab in CD patients of the Madrid area, looking for clinical predictors of response.Multicenter retrospective survey of all CD patients treated with infliximab in 8 University hospitals of the Madrid area (Spain) with a minimum follow up of 14 wks.169 patients included (48%males, mean age 39 +/- 12 yrs). 64% of them had perianal disease. 82% were under immunosuppressants. 1,355 infliximab infusions administered (mean 8, range 1-30). 90% response rate and 48% remission rate were obtained with induction therapy. 73% followed maintenance treatment, and 78% of them maintained or improved the response after a mean follow up of 28 months (range 3.5-86). 24 patients lost response during the follow up, after a mean of 41 wks (range 6-248). Only the prescription of maintenance therapy was predictive factor for favourable response (p0.01). 17 infusion reactions were reported (10% of the patients, 1.2% of the infusions; only one case was severe) and were the cause of treatment withdrawal in 7 patients. Co-treatment with immunosuppressive drugs and maintenance infliximab therapy were protective factors for infusion reactions (p0.05). Other adverse events occurred in 26% of the patients, and were cause of treatment withdrawal in 7 patients.Infliximab is effective and safe for CD management but concomitant immunosuppressive drugs and maintenance treatment should be prescribed to obtain the best outcome. That confirms in a real life clinical setting the favourable results obtained in randomized clinical trials.

To determine the prevalence of immune-mediated inflammatory diseases (IMID) in a cohort of patients with inflammatory bowel disease (IBD) enrolled in hospital gastroenterology outpatients units for the AQUILES study, a prospective 2-year follow-up study.We included patients ≥18 years old with a prior or new diagnosis of IBD (Crohn disease [CD], ulcerative colitis [UC] or indeterminate colitis). Diagnoses were collected in a cross-sectional manner from the clinical records at enrollment of a new patient in the study.We included 526 patients (mean age 40.2 years; 47.3% men, 52.7% women), 300 with CD (57.0%), 218 with UC (41.4%) and 8 with indeterminate colitis. Other types of IMID were present in 71 patients (prevalence: 13.5%, 95% CI: 10.8-16.7): 47 were spondyloarthropathies (prevalence: 8.9%); 18 psoriasis (3.4%); 5 pyoderma gangrenosum (1.0%), and 11 uveitis (2.1%). The prevalence of IMID was higher in patients with CD than in those with UC (17.0% [95% CI: 13.2-21.7] vs 9.2% [95% CI: 6.0-13.8], p=0.011). In the multivariate analysis, the variables associated with the presence of IMID were diagnosis of CD (OR=1.8 [95% CI: 1.1-3.2]) and duration of IBD ≥4 years (OR=2.1 [95% CI: 1.1-4.1] in those with disease duration 4-8 years, and OR=2.1 [95% CI: 1.2-3.9] in those with ≥8 years vs.4 years).In the cohort of patients with IBD in the AQUILES study, 13.5% had another IMID, with a higher prevalence in patients with CD and4 years since disease onset.

Background Methotrexate is useful in inflammatory bowel disease (IBD), but its role is secondary because of its limited experience and a supposedly unfavorable safety profile. Aim To describe the efficacy and safety of methotrexate in a long-term real clinical practice. Methods Retrospectively reviewed records of IBD patients treated with methotrexate in eight hospitals of Madrid (Spain). Results A total of 77 patients were included (80% Crohn’s disease); 94% received methotrexate because of steroid dependency. Overall, 82% of the patients initially responded (28% remission). Eighty-eight percent of the patients followed maintenance treatment for a mean of 17 (range: 1–108) months. Forty percent of the patients lost response at a mean of 57 weeks after starting methotrexate. No statistically significant differences were found in the response rates in terms of the disease type, route of administration, or the Montreal Classification category. The mean methotrexate cumulative dose was 1108 mg (range: 25–6480). The main adverse events included 10 cases of gastrointestinal symptoms, four of myelotoxicity, and 10 of abnormal liver function tests, and led to methotrexate withdrawal in four (5%) patients. Transient elastography, performed in 46 patients, detected six additional cases with significant fibrosis and normal liver function tests. Conclusion Methotrexate is useful in inducing a response in IBD, although its efficacy decreases frequently through the follow-up. Although methotrexate seems safe in the long term, in addition to biochemical controls, a more accurate method to detect liver damage should be considered.

Hepatitis B virus (HBV) is a very common infection worldwide. Its reactivation in patients receiving immunosuppression has been widely described as being associated with significant morbidity and mortality unless anti-viral prophylaxis is administered. Treatment in inflammatory bowel disease (IBD) patients has changed in recent years and immunosuppression and biological therapies are now used more frequently than before. Although current studies have reported an incidence of hepatitis B in inflammatory bowel disease patients similar to that in the general population, associated liver damage remains an important concern in this setting. Liver dysfunction may manifest in several ways, from a subtle change in serum aminotransferase levels to fulminant liver failure and death. Patients undergoing double immunosuppression are at a higher risk, and reactivation usually occurs after more than one year of treatment. As preventive measures, all IBD patients should be screened for HBV markers at diagnosis and those who are positive for the hepatitis B surface antigen should receive antiviral prophylaxis before undergoing immunosuppression in order to avoid HBV reactivation. Tenofovir/entecavir are preferred to lamivudine as nucleos(t)ide analogues due to their better resistance profile. In patients with occult or resolved HBV, viral reactivation does not appear to be a relevant issue and regular DNA determination is recommended during immunosuppression therapy. Consensus guidelines on this topic have been published in recent years. The prevention and management of HBV infection in IBD patients is addressed in this review in order to address practical recommendations.

Aim Anti-tumor necrosis factor (TNF)-alpha agents are widely used for the treatment of both inflammatory bowel disease (IBD) and psoriasis. Psoriatic skin lesions induced by anti-TNF have been described in patients with IBD. We report a case series of psoriasis induced by anti-TNF agents in IBD patients. Methods Systematic analysis of cases of psoriasis induced by anti-TNF in an IBD patient cohort in tertiary hospitals of Madrid. Results A total of 21 of 1294 patients with IBD treated with anti-TNF-alpha agents developed drug-induced psoriasis (cumulative incidence 1.62%; 95% CI 1.06%–2.47%): 14 patients with infliximab and 7 with adalimumab; seventeen with Crohn's disease, 4 with ulcerative colitis. The onset of skin lesions varied in a wide range of time (after a mean 13 ± 8 doses). The most frequent site of skin lesions was the limbs (62%) followed by the trunk (48%) and the scalp (43%). The psoriasis phenotypes were plaque psoriasis (57%), scalp (14%), palmoplantar pustulosis (14%), pustular generalized psoriasis (5%), guttate (5%) and inverse (5%). Four patients interrupted the anti-TNF treatment, and that led to the complete regression of lesions in 1 of them. The other 17 patients were maintained on anti-TNF therapy and managed with topical steroids. Conclusion Psoriatic lesions can be induced by anti-TNF drugs. Plaque psoriasis on the extremities and trunk were the most frequent presentations in our series. Topical steroid treatment is effective in most patients. Anti-TNF discontinuance may be reserved for patients with severe psoriasis or patients without response to topical therapy.

Adalimumab Dose Escalation Is Effective for Managing Loss of Response in Ulcerative Colitis Carlos Taxonera, Eva Iglesias Flores, Fernando Munoz, Marta Calvo, Manuel Barreiro-de Acosta, David Busquets, Xavier Calvet, Antonio Rodriguez, R. Pajares, Javier P. Gisbert, Pilar Lopez-Serrano, Jose Lazaro Perez-Calle, Angel Ponferrada Diaz, Cristobal De la Coba, Fernando Bermejo, Maria Chaparro, Cristina Alba, David Olivares, Ignacio Fernandez-Blanco

Currently immunosuppressive and biological agents are used in a more extensive and earlier way in patients with inflammatory bowel disease, rheumatic or dermatologic diseases. Although these drugs have shown a significant clinical benefit, the safety of these treatments is a challenge. Hepatitis B virus (HBV) reactivations have been reported widely, even including liver failure and death, and it represents a deep concern in these patients. Current guidelines recommend to pre-emptive therapy in patients with immunosuppressants in general, but preventive measures focused in patients with corticosteroids and inflammatory diseases are scarce. Screening for HBV infection should be done at diagnosis. The patients who test positive for hepatitis B surface antigen, but do not meet criteria for antiviral treatment must receive prophylaxis before undergoing immunosuppression, including corticosteroids at higher doses than prednisone 20 mg/d during more than two weeks. Tenofovir and entecavir are preferred than lamivudine because of their better resistance profile in long-term immunosuppressant treatments. There is not a strong evidence, to make a general recommendation on the necessity of prophylaxis therapy in patients with inflammatory diseases that are taking low doses of corticosteroids in short term basis or low systemic bioavailability corticosteroids such as budesonide or beclomethasone dipropionate. In these cases regularly HBV DNA monitoring is recommended, starting early antiviral therapy if DNA levels begin to rise. In patients with occult or resolved hepatitis the risk of reactivation is much lower, and excepting for Rituximab treatment, the prophylaxis is not necessary.

(p = 0.013) during follow-up of the cohort. No statistical significance was obtained regarding the need for biological therapy or surgery. Statistically significant association between smoking and need for hospitalization was also found in CD (p = 0.004). There is also a significant association between younger age at diagnosis and biological therapy need (p = 0.022) and between B3 pattern and need for immunomodulatory therapy (p = 0.009). The B1 pattern was associated with less hospitalization (p = 0.049) and less need for surgery (p = 0.018). For UC no statistically significant association between the independent variables of the patients, disease phenotype and therapeutic needs was found. Conclusions: In our hospital area of southern Spain incidence rates are similar to other areas of southern Europe. However Greater incidence of Crohn’s disease with respect to UC is described. Crohn’s disease requires more aggressive therapy than CU (immunomodulators and surgery). An early age at diagnosis is associated with greater need for biologic therapy.

DOP071 Inflammatory bowel diseases: a new cardiovascular risk factor? L. Caillo1 *, G. Danan1, V. Georgescu2, L. Papineau1, F. Gonzalez1, J.-F. Bourgaux3, F. Guillon4, G.-P. Pageaux1, R. Altwegg1 *. 1University Hospital of St Eloi, Departement of Hepatology and Gastroenterology, Montpellier, France, 2University Hospital, Department of Medical Information, Montpellier, France, 3University Hospital, Department of Hepatology and Gastroenterology, Nimes, France, 4University Hospital of St Eloi, Department of Digestive Surgery, Montpellier, France

Inflammatory bowel disease patients are prone to immunosuppression due to effects of their medications. Physicians are recommended to assess vaccination status and overall health in all patients, prior to initiation of immunosuppressive therapy. Immunosuppressant medications in women with inflammatory bowel disease are often continued during pregnancy, which can result in newborns having an increased risk of immunosuppression at birth. While medication-induced immunosuppression in infants is transient, parents should be counselled about delaying live vaccine administration in newborns until they are immune competent. A retrospective study was done over six months at an urban multispecialty medical center to assess whether physicians are counselling pregnant immunosuppressed inflammatory bowel disease patients regarding live vaccinations in their newborns. The study revealed that only 57% of patients had documented counselling in their charts. Further studies are necessary to determine physician counselling practices of pregnant women about live vaccines. It is critical that physicians and patients are aware of the risks of immunosuppression in pregnancy and the potential impact of live vaccines upon the newborn.

M.J. Casanova1, M. Chaparro1 *, E. Domenech2, M. Barreiro-de Acosta3, F. Bermejo4, E. Iglesias5, F. Gomollon6, L. Rodrigo7, X. Calvet8, M. Esteve9, E. Garcia-Planella10, S. Garcia11, C. Taxonera12, M. Calvo13, M. Lopez14, D. Ginard15, M. Gomez16, E. Garrido17, J. Perez-Calle18, B. Beltran19, M. Piqueras20, C. Saro21, B. Botella22, C. Duenas23, A. Ponferrada24, M. Manosa2, M. Iglesias3, A. Algaba4, V. Garcia-Sanchez5, J. Mate1, J.P. Gisbert1. 1Hospital Universitario de La Princesa, IP, Gastroenterology and CIBEREHD, Madrid, Spain, 2Hospital Germans Trias i Pujol, Badalona, Spain, 3Hospital Clinico Santiago, Santiago de Compostela, Spain, 4Hospital de Fuenlabrada, Madrid, Spain, 5Hospital Reina Sofia, Cordoba, Spain, 6Hospital Clinico Lozano Blesa, Zaragoza, Spain, 7Hospital Central de Asturias, Asturias, Spain, 8Hospital Parc Tauli, Barcelona, Spain, 9Hospital Mutua de Terrassa, Terrassa, Spain, 10Hospital Santa Creu i Sant Pau, Barcelona, Spain, 11Hospital Miguel Servet, Zaragoza, Spain, 12Hospital Clinico San Carlos, Madrid, Spain, 13Hospital Puerta de Hierro, Madrid, Spain, 14Hospital de Galdakao, Galdakao, Spain, 15Hospital Son Espases, Mallorca, Spain, 16Hospital Virgen de Las Nieves, Granada, Spain, 17Hospital Ramon y Cajal, Madrid, Spain, 18Hospital Fundacion Alcorcon, Madrid, Spain, 19Hospital La Fe, Valencia, Spain, 20Consorcio Sanitario Terrassa, Terrassa, Spain, 21Hospital de Cabuenes, Gijon, Spain, 22Hospital Infanta Cristina, Madrid, Spain, 23Hospital San Pedro Alcantara, Caceres, Spain, 24Hospital Infanta Leonor, Madrid, Spain

Introduction: A significant proportion of Crohn's Disease (CD) patients have already been treated with two biologic therapies. Follow-up from current published retrospective or prospective open label studies on patients who have already received 2 biologics does not extend beyond 1 year (1-4) Methods: Our aim was to collect ‘real-life', long-term data on the tolerability and efficacy of the second biologic agent in (re)-capturing response, and to assess whether the reason for stopping the first agent impacted on the successful use of the second agent. We carried out secure data collection from 3 teaching IBD centres on CD patients currently on, or already failed a second biologic. We collected data on disease duration, distribution and behaviour, and report on the aetiology in the failure of the first biologic and the subsequent outcome of the second biologic agent. Response to biologics was assessed by Harvey Bradshaw Index or Physicians Global Assessment. Results: We collected data on 66 patients (F 46%, mean age at diagnosis: 25). The disease distribution was characterised as L1: 11%, L2:32% L3:56% L4:1% and the behaviour as B1: 41% B2: 35% B3: 24% . 17% of our cohort had perianal involvement. 36 patients have had a total of 41 resectional operations. 1st biologic: 64/66 patients had infliximab (IFX) first-line, followed by adalimumab (ADA), and 2/66 patients had ADA followed by IFX. Reasons for swapping were 1o failure in 23%, secondary-loss of response in 38%, intolerance to the first agent in 29%, and fear of hypersensitivity reaction due to previous episodic exposure to IFX in 10% (irrespective of efficacy or tolerance) 2nd biologic: 70% of patients remained on the second biologic after a median follow-up of 22 months. Reasons for discontinuing therapy were 1o failure in 35%, secondary loss of response in 25%, intolerance (or patient concerns regarding potential side-effects) in 25%, and achieving remission in 5%; no reason provided for the remainder 5%. Neither the demographics, disease characteristics nor the reason for failing the first biologic had a statistically significant bearing in predicting the initial response to and subsequent outcome of the second biologic. Conclusion: 1. We report an overall 70% retention on the second biologic at 22 months following all-cause failure of the first agent in CD patients from England and Ireland. 2. Patients responded equally well to the second biologic, irrespective of the reason for the failure of the first biologic. References: 1.Swaminath A et al, APT 2009 2. Seiderer J et al, APT 2007, Peyrin-Biroulet L et al, APT 2007, 4. Papadakis KA et al, AJG 2005.