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Background: It is unknown which maintenance therapy is the most effective option for patients admitted for an acute severe ulcerative colitis (ASUC) episode responding to intravenous steroids., Methods: We conducted a multicentre, parallel-group, open-label randomised controlled trial among 23 French centres in thiopurine and biologics-naïve adults admitted for ASUC responding to intravenous steroids. Eligible patients were randomly assigned to receive infliximab (IFX) and azathioprine (AZA) with a 7-day steroid tapering scheme (IFX+AZA arm) or AZA and conventional standardised steroid tapering regimen (AZA arm). The primary composite endpoint was treatment failure at week 52, defined as the absence of steroid-free clinical remission, the absence of endoscopic response, the use of a prohibited treatment for relapse, severe adverse event leading to treatment interruption, colectomy or death. Multiple imputation for missing data was performed., Findings: Among the 64 patients randomised (Lichtiger score 13.5±2.0; median age of 34.5 (P25-P75 26.3-50.3) years, median C reactive protein of 29.0 (12.8-96.8) mg/L at baseline): 32 were assigned to the IFX+AZA arm and 32 to the AZA arm. In the ITT population, treatment failure at week 52 was observed in 22/27 (81.5%) in the AZA arm and 16/30 (53.3%) in the IFX+AZA arm (risk ratio 3.85, 95% CI (1.15 to 12.88), p=0.03). 29 adverse events were severe, including 13 disease exacerbations, 6 severe infections without any difference between both arms., Interpretation: Combination therapy with IFX+AZA was more effective at 1 year than AZA alone to avoid treatment failure in patients with ASUC responding to intravenous steroids., Trial Registration Number: NCT02425852., Competing Interests: Competing interests: AA received consulting fees from Abbvie, Pfizer, Takeda, Tillotts Pharma, Janssen and Sandoz as well as lecture fees and travel accommodations from Abbvie, Janssen, Pfizer, Takeda, Biogen, Fresenius Kabi, Amgen and Celltrion. PS reports consulting fees from Pfizer, Astellas, Janssen, Fresenius Kabi, Takeda, Abbvie, Merck-MSD, Pilège, Lilly, Celltrion and Biocodex; and grants from Biocodex and Janssen. CS declare lecture and/or consulting fees from Abbvie, Amgen, Celltrion, Janssen, Lilly, Takeda, Tillots. PW received board membership, consultancy, or lecture fees from Abbvie, Amgen, Celltrion, Ferring, Janssen, and Takeda. LV received fees from Abbvie, Amgen, MSD, Ferring, Takeda, Pfizer, Celltrion, Janssen, Galapagos, Dr Falk. RA declares lecture fees from MSD, Abbvie, Pfizer, Takeda, and Janssen. GB received lecture fees from Abbvie, Ferring, Takeda and Pfizer and consultant fees from Takeda, Janssen, Lilly, Celltrion, Sandoz, Abbvie. MB has received lecture fees and travel accommodation from Abbvie, Fresenius Kabi, Janssen, Pfizer and Takeda. DL has received counseling, boards, transports and/or fees from Abbvie, Amgen, Biogen, Ferring, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, Prometheus, Roche, Takeda, Tillots. MA has served as a speaker, consultant, and/or advisory board member for Abbvie, Amgen, Biogen, Boehringer-Ingelheim, Celgene, Celltrion, Ferring, Galapagos, Genentech, IQVIA, Janssen, Lilly, MSD, Pfizer, Roche, Takeda, Tillotts. FG declares counseling, boards, transports and lectures fees from Abbvie, Amgen, Biogen, Celltrion, Janssen, Lilly, MSD, Pfizer, Takeda. NR has received lecture fees from AbbVie and Takeda. LP-B received consulting fees from Merck, Abbvie, Janssen, Genentech, Ferring, Norgine, Tillots, Vifor, Shire, Therakos, Pharmacosmos, Pilège, BMS, UCB-Pharma, Hospira, Celltrion, Takeda, Biogaran, Boerhinger-Ingelheim, Lilly, Pfizer and HAC-Pharma. This author also received lecture fees from Merck, Abbvie, Takeda, Janssen Cilag, Ferring, Norgine, Tillots, Vifor, Therakos, HAC-Pharma and Mitsubishi. No conflicts of interest are claimed by the remaining authors., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The exact rate of contraindications to anti-TNF therapy and physician perspectives on treatment choices facing to anti-TNF contraindication, are poorly reported., Methods: A two-week cross-sectional study was conducted in 31 centres. Physicians completed a questionnaire for a total of 1,314 consecutive outpatients with Crohn's disease, assessing each patient's potential contraindications to anti-TNF therapy, the choice of alternative therapy to anti-TNFs, and their preference in an unrestricted reimbursement setting., Results: Among the 1,293 responses to the first item, 148 (11.5%) reported 32 absolute contraindications (2.5%) and 116 relative contraindications (9.0%) to anti-TNF therapy. When asked about their preference of alternative therapies in those cases with contraindications to anti-TNF, physicians chose ustekinumab and vedolizumab, 75.6% and 23.9%, respectively. In multivariable analysis, the choice of vedolizumab was the preferred choice for patients aged > 60 years with the L2 phenotype and the absence of perianal lesions. In a hypothetical setting of unrestricted reimbursement, anti-TNFs remained physicians' preferred first-line biological therapy choice for 78.2%., Conclusion: Anti-TNF contraindications occurred in up to 11.5% of patients with Crohn's disease. Physicians' choices for alternative therapy to anti-TNF relied on ustekinumab in 75.6% and vedolizumab in 23.9% of these cases. This choice was driven mainly by phenotypical criteria and age., Competing Interests: Declaration of Competing Interest Maria Nachury has received lecture and consulting fees from Abbvie, Adacyte, Amgen, Arena, Biogen, CTMA, Ferring, Gilead, Janssen, Mayoli Spindler, MSD, Pfizer, Takeda Melanie Serrero has received lecture or consulting fees from Abbvie, Ferring, Amgen, Celltrion, Janssen, Ferring, Takeda and Tillotts. Philippe Seksik received consulting fees from Takeda, Abbvie, Merck-MSD, Biocodex, Janssen, Amgen, Astellas and Pfizer, grants from Biocodex and travel accommodation from Merck-MSD, Takeda and Amgen. Charlotte Gagniere received transport fees from Takeda Arnaud Bourreille received counselling, boards or transport fees from Abbvie, Janssen, Ferring, MSD, Novartis, Pfizer, Takeda and Tillotts Pharma. Stéphane Nahon reported a relationship with Janssen, Pfizer, Takeda, MSD, Gilead, Ferring Marion Simon reported a relationship with Abbvie, Mylan, Takeda and Amgen Lucas Guillo has received lecture and consulting fees from Abbvie Xavier Roblin reported a relationship with MSD, Pfizer, Celltrion, Abbvie, Amgen, Takeda, Janssen, Ferring, Theradiag. Anthony Buisson has received research funding from Pfizer, lecture fees from Abbvie, Ferring, Hospira, MSD, Janssen, Sanofi-Aventis, Takeda and Vifor Pharma and consulting fees from Abbvie, Biogen, Janssen, Pfizer and Takeda. Stephane Nancey has received consulting fees from Merck, Abbvie, Takeda, Ferring, Norgine, Vifor Pharma, Novartis, Janssen Cilag, Hospira, Takeda and HAC Pharma Vered Abitbol has received lecture fees from Amgen, Biogen, Mylan, Sandoz, Pfizer, Takeda, Janssen, Tillots, Gilead, Ferring Jean-Marie Reimund has received consulting fees from Hospira and Pfizer. This author has also received lectures fees from Abbvie, Biocodex, Ferring, Janssen Cilag, Pfizer and Takeda, as well as travel accommodations from Ferring, Abbvie, MSD, Janssen Cilag, Pfizer, Hospira and Takeda Lucine Vuitton has received lecture fees from Abbvie, MSD, Takeda, Ferring, Janssen, Amgen, Gilead, Celltrion and Pfizer, and research grants from MSD, Takeda and Pfizer. Laurent Peyrin-Biroulet has received consulting fees from Merck, Abbvie, Janssen, Genentech, Ferring, Norgine, Tillots, Vifor, Shire, Therakos, Pharmacosmos, Pilège, BMS, UCB-Pharma, Hospira, Celltrion, Takeda, Biogaran, Boerhinger-Ingelheim, Lilly, Pfizer, and HAC-Pharma. This author has also received lecture fees from Merck, Abbvie, Takeda, Janssen Cilag, Ferring, Norgine, Tillots, Vifor, Therakos, HAC-Pharma, and Mitsubishi. Cyrielle Gilletta received lecture fees from Abbvie, Takeda, Pfizer and Janssen and consulting fees from Abbvie, Janssen and Takeda. Matthieu Allez has received honoraria from Novo Nordisk, MSD, Abbvie, Ferring, Genentech, Janssen, Pfizer, GSK, Hospira, UCB, Novartis, Takeda, Mayolo-Spindler. Stephanie Viennot has received consulting fees from Abbvie, MSD, Takeda, Vifor Pharma and Ferring. Claire Painchart has received travel accommodation from Abbvie, Janssen, Biogene, Fresenius Kabi, Takeda and Pfizer. Mathurin Fumery has received lecture and consulting fees from Abbvie, MSD, Boehringer, Pfizer, Takeda, Janssen and Ferring. David Laharie has received counseling, boards, transports and/or fees from Abbvie, Biogaran, Biogen, Ferring, HAC-pharma, Janssen, MSD, Novartis, Pfizer, Prometheus, Roche, Takeda, Theradiag, Tillots. Aurelien Amiot has received consulting fees from Abbvie, Hospira, Takeda, Gilead and Biocodex as well as lecture fees and travel accommodations from Abbvie, Janssen, Biocodex, Hospira, Ferring, Takeda and MSD. This author has also received advisory board fees from Gilead, Takeda and Abbvie. No conflicts of interest are claimed by the remaining authors., (Copyright © 2022 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Introduction: New therapeutic options for patients with Crohn's disease (CD) with perianal lesions failing anti-tumor necrosis factor (TNF) agents are needed. We aimed to assess the effectiveness of ustekinumab in perianal CD (pCD) and predictors of clinical success in a real-life multicenter cohort., Methods: We conducted a national multicenter retrospective cohort study in patients with either active or inactive pCD who received ustekinumab. In patients with active pCD at treatment initiation, the success of ustekinumab was defined by clinical success at 6 months assessed by the physician's judgment without additional medical or surgical treatment for pCD. Univariate and multivariable logistic regression analyses were performed to identify predictors of success. In patients with inactive pCD at ustekinumab initiation, the pCD recurrence-free survival was calculated using the Kaplan-Meier method., Results: Two hundred seven patients were included, the mean age was 37.7 years, the mean duration of CD was 14.3 years, and the mean number of prior perianal surgeries was 2.8. Two hundred five (99%) patients had previously been exposed to at least 1 anti-TNF and 58 (28%) to vedolizumab. The median follow-up time was 48 weeks; 56/207 (27%) patients discontinued therapy after a median time of 43 weeks. In patients with active pCD, success was reached in 57/148 (38.5%) patients. Among patients with setons at initiation, 29/88 (33%) had a successful removal. The absence of optimization was associated with treatment success (P = 0.044, odds ratio 2.74; 95% confidence interval: 0.96-7.82). In multivariable analysis, the number of prior anti-TNF agents (≥3) was borderline significant (P = 0.056, odds ratio 0.4; 95% confidence interval: 0.15-1.08). In patients with inactive pCD at initiation, the probability of recurrence-free survival was 86.2% and 75.1% at weeks 26 and 52, respectively., Discussion: Ustekinumab appears as a potential effective therapeutic option in perianal refractory CD. Further prospective studies are warranted.

Background: The management of Crohn's disease patients with perianal lesions and anti-TNF failure is challenging., Aims: To assess the effectiveness of vedolizumab in perianal Crohn's disease and the predictors of success in a real-life cohort., Methods: We conducted a nationwide multicentre cohort study in patients with perianal Crohn's disease who received vedolizumab. In patients with active perianal Crohn's disease, the success of vedolizumab was defined by clinical success (no draining fistula at clinical examination and no anal ulcers for primary lesions) at 6 months without medical or surgical treatment for perianal Crohn's disease. Logistic regression analyses were performed to identify predictors of success. In patients with inactive perianal Crohn's disease, recurrence was defined by the occurrence of lesions and/or the need for medical or surgical treatments., Results: One hundred and fifty-one patients were included. Among them 102 patients had active perianal disease, 33 (32.4%) males, mean age 39.8 years, mean Crohn's disease duration 14.6 years; 101 (99%) had received at least one anti-TNF. The median follow-up time was 52 weeks. Sixty-eight per cent of patients discontinued therapy after a median time of 33 weeks. Vedolizumab success was reached in 23/102 (22.5%). Among patients with setons at initiation, 9/61(15%) had a successful removal. In multivariable analysis, factors associated with success were the number of prior biologic agents (≥3, odds ratio, OR: 0.20, 95% CI 0.04-0.98) and no antibiotics at initiation (OR: 4.76, 95% CI 1.25-18.19). In 49 patients with inactive perianal Crohn's disease, perianal disease recurred in 15/49 (30.6%), 11/49 (22.4%) needed dedicated treatments. Median time to recurrence was 22 weeks., Conclusions: We identified a low rate of success of vedolizumab in patients with active perianal Crohn's disease, and nearly one third of patients with inactive perianal Crohn's disease had perianal recurrence. Further evaluation is warranted in prospective studies., (© 2020 John Wiley & Sons Ltd.)

Aim: to describe the characteristics of incident cases of tuberculosis [TB] despite negative TB screening tests, in patients with inflammatory bowel disease [IBD] undergoing anti-TNF treatment, and to identify the risk factors involved., Methods: A retrospective descriptive study was conducted at GETAID centers on all IBD patients undergoing anti-TNF treatment who developed TB even though their initial screening test results were negative. The following data were collected using a standardized anonymous questionnaire: IBD, and TB characteristics and evolution, initial screening methods and results, and time before anti-TNF treatment was restarted., Results: A total of 44 IBD patients [including 23 men; median age 37 years] were identified at 20 French and Swiss centers at which TB screening was performed [before starting anti-TNF treatment] based on Tuberculin Skin Tests [n = 25], Interferon Gamma Release Assays [n = 12], or both [n = 7]. The median interval from the start of anti-TNF treatment to TB diagnosis was 14.5 months (interquartile range [IQR] 25-75: 4.9-43.3). Pulmonary TB involvement was observed in 25 [57%] patients, and 40 [91%] had at least one extrapulmonary location. One TB patient died as the result of cardiac tamponade. Mycobacterium tuberculosis exposure was thought to be a possible cause of TB in 14 cases [32%]: 7 patients [including 6 health care workers] were exposed to occupational risks, and 7 had travelled to endemic countries. Biotherapy was restarted on 27 patients after a median period of 11.2 months [IQR 25-75: 4.4-15.2] after TB diagnosis without any recurrence of the infection., Conclusion: Tuberculosis can occur in IBD patients undergoing anti-TNF treatment, even if their initial screening results were negative. In the present population, TB was mostly extrapulmonary and disseminated. TB screening tests should be repeated on people exposed to occupational risks and/or travelers to endemic countries. Restarting anti-TNF treatment seems to be safe., (Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Methotrexate is proposed for the treatment of inflammatory disorders such as rheumatoid arthritis, psoriasis and Crohn's disease. The liver toxicity of methotrexate has been investigated and prolonged treatment can induce liver fibrosis. Moreover, alcohol consumption, diabetes and obesity are associated with liver fibrosis in patients treated with this drug. Therefore, liver fibrosis associated with methotrexate could be due to associated factors instead of methotrexate itself. Recommendations to monitor and diagnose methotrexate induced liver damage vary depending on the disease. Frequent evaluation of liver fibrosis with liver biopsy is recommended during therapy, especially in patients treated for psoriasis. Noninvasive methods, such as the FibroScan, could be useful for the assessment of liver fibrosis associated with methotrexate and hence, need further evaluation.