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Background: Hypersensitivity reactions (HSR) to the administration of infliximab (IFX) in Inflammatory Bowel Diseases (IBD) patients are not rare and usually lead to drug discontinuation. We report data on safety and effectiveness of desensitization to IFX in patients with previous HSR., Methods: We conducted a retrospective monocentric observational study. Patients for whom a desensitization protocol to IFX was realized after a previous HSR were included. Anti-drug antibodies (ADA) and IFX trough levels at both inclusion and six months after desensitization were collected. Clinical outcomes, including recurrence of HSR were evaluated., Results: From 2005 to 2020, 27 patients (Crohn's Disease: 26 (96%) were included). Desensitization after HSR was performed after a median time of 10.4 months (2.9-33.1). Nineteen (70%) patients received immunosuppressants at time of desensitization. Eight (30%) patients presented HSR at first ( n  = 2), second ( n  = 4) or third ( n  = 2) IFX perfusion after desensitization. None led to intensive care unit transfer or death. Thirteen (48%) had clinical response at 6 months and 8 (29%) were still under IFX treatment two years after desensitization. IFX trough levels and ADA were available for 14 patients at time of desensitization. Most patients (12 out of 14) had ADA at a high level. At 6 months, among the 7 patients with long term response to IFX, 4 presented a decrease of ADA titers and 2 had a significant trough level of IFX., Conclusion: IFX desensitization in patients with IBD is a safe therapeutic alternative and represents a potential option for patients refractory to multiple biologics. What is already known? Hypersensitivity reactions to the administration of infliximab is frequent. Occurrence of hypersensitivity reaction, either immediate or delayed, usually leads to permanent drug discontinuation. What is new here? Infliximab desensitization is well tolerated with no hypersensitivity reaction recurrence in 70% of patients. Clinical success at 6 months was of 48% and around a third of patients remained under infliximab therapy two years after desensitization. Antidrug antibodies decreased and infliximab trough levels increased in these patients showing the impact of desensitization on immunogenicity. How can this study help patient care? Infliximab desensitization represents a potential option for patients refractory to multiple biologics who presented hypersensitivity reaction to the drug.

Background: In recent years, an increasing prevalence of obesity in inflammatory bowel disease (IBD) has been observed. However, only a few studies have focused on the impact of overweight and obesity on IBD-related disability., Aims: To identify the factors associated with obese and overweight patients with IBD, including IBD-related disability., Patients and Methods: In this cross-sectional study, we included 1704 consecutive patients with IBD in 42 centres affiliated with the Groupe d'Etude Therapeutique des Affections Inflammatoires du tube Digestif (GETAID) using a 4-page questionnaire. Factors associated with obesity and overweight were assessed using univariate and multivariate analyses (odds ratios (ORs) are provided with 95% confidence intervals)., Results: The prevalence rates of overweight and obesity were 24.1% and 12.2%, respectively. Multivariable analyses were stratified by age, sex, type of IBD, clinical remission and age at diagnosis of IBD. Overweight was significantly associated with male sex (OR = 0.52, 95% CI [0.39-0.68], p < 0.001), age (OR = 1.02, 95% CI [1.01-1.03], p < 0.001) and body image subscore (OR = 1.15, 95% CI [1.10-1.20], p < 0.001) (Table 2). Obesity was significantly associated with age (OR = 1.03, 95% CI [1.02-1.04], p < 0.001), joint pain subscore (OR = 1.08, 95% CI [1.02-1.14], p < 0.001) and body image subscore (OR = 1.25, 95% CI [1.19-1.32], p < 0.001) (Table 3)., Conclusion: The increasing prevalence of overweight and obesity in patients with IBD is associated with age and poorer body image. A holistic approach to IBD patient care should be encouraged to improve IBD-related disability and to prevent rheumatological and cardiovascular complications., Competing Interests: Declaration of Competing Interest Yoram Bouhnik received lecture and consulting fees from Abbvie, Biogaran, Boehringer-Ingelheim, CTMA, Ferring, Gilead, Hospira, ICON, Inception IBD, Janssen, Lilly, Mayoli Spindler, Merck, MSD, Norgine, Pfizer, Robarts Clinical Trials, Roche, Sanofi, Shire, Takeda, UCB and Vifor Pharma. This author has also stock ownership of Inception IBD, San Diego, CA, USA. Melanie Serrero has received lecture or consulting fees from Abbvie, Ferring, Amgen, Celltrion, Janssen, Ferring, Takeda and Tillotts. Jerome Filippi has received lecture and consulting fees from Abbvie, Amgen, Biogen, Ferring, HAC Pharma, Janssen, MSD, Pfizer, Sandoz and Takeda. Xavier Roblin reported a relationship with MSD, Abbvie, Amgen, Sandoz, Pfizer, Takeda and Janssen. Guillaume Bouguen received lecture fees from Abbvie, Ferring, MSD, Takeda and Pfizer and consultant fees from Takeda, Janssen. Denis Franchimont is research director of FNRS; he has received educational grants from Abbvie, Takeda, MSD, and has received honoraria fees for lectures or consultancy from Ferring, Falk, Chiesi, Abbvie, MSD, Centocor, Pfizer, Amgen, Janssen, Mundipharma, Takeda and Hospira. Guillaume Savoye has received lecture fees from Vifor Pharma, Takeda, Pfizer, HAC Pharma, Abbvie, MSD, and Ferring France. This author has also received travel accommodations from Ferring, Abbvie, and MSD France as well as a research grant from Ferring. 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. Edouard Louis has received fees for: Research Grant: Takeda, Pfizer; Educational Grant: Abbvie, Takeda, Janssen; Speaker Fees: Abbvie, Ferring, MSD, Falk, Takeda, Hospira, Janssen, Pfizer, Celgene; Advisory Board: Abbvie, Ferring, MSD, Takeda, Celgene, Hospira, Janssen; Consultant: Abbvie 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 Olivier DeWit declares counseling, boards, transport or personal fees from Abbvie, BMS, Celltrion, Ferring, Galapagos, Janssen, Mylan, Pfizer, and Takeda Lucine Vuitton has received lecture fees from Abbvie, MSD, Takeda, Ferring, Janssen and Pfizer, and research grants from MSD, Takeda and Pfizer. Nicolas Mathieu has received consulting fees from Celltrion, Mylan, MSD, Gilead, Sandoz and lecture fees from Abbvie, Amgen, Biogen, Janssen, MSD, Pfizer, Takeda 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. Catherine Le Berre has served as a consultant for Abbvie, Janssen and Gilead; reports receiving payment for lectures from AbbVie, Celltrion, Ferring, Fresenius Kabi, Galapagos, Janssen, MSD, Pfizer and Takeda. Medina Boualit has received travel accommodation from Abbvie, Janssen Takeda and Pfizer. Lucile Boivineau has received consulting fees from Abbvie and Tillotts. Mathurin Fumery has received lecture and consulting fees from Abbvie, MSD, Boehringer, Pfizer, Takeda, Janssen and Ferring. Ludovic Caillo received board and lecture fees from Abbvie, Janssen, Pfizer, Takeda, Amgen 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. Maria Nachury has received lecture and consulting fees from Abbvie, Adacyte, Amgen, Arena, Biogen, CTMA, Ferring, Gilead, Janssen, Mayoli Spindler, MSD, Pfizer, Takeda, Viatris 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 © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Introduction: Extraintestinal manifestations (EIMs) of inflammatory bowel disease (IBD) are challenging clinical situation. No prospective study assessed remission risk factors of EIMs. The aim of this study was to prospectively investigate the epidemiology, risk factors of EIM occurrence, and EIM remission in a large IBD cohort., Methods: We conducted a cross-sectional study in 30 French referral centers. Between May 2021 and June 2021, all consecutive patients attending to hospital appointment were systematically invited to fill out a questionnaire., Results: A total of 1,971 consecutive patients with IBD were analyzed. There were 1,056 women (53.8%), and the median age of patients was 41 years (31-54). The median disease duration was 11 years (1-18). Overall, 544 (27.6%) had at least 1 EIM. In 20.2% of cases, patients had multiple EIMs. The most frequent EIMs were rheumatological (19%) and dermatological (10%) manifestations. Immunosuppressant treatment (odds ratio [OR] = 2.56; P < 0.001) was a risk factor of EIM, while the Montreal A3 classification (OR = 0.61, P = 0.023) and male gender (OR = 0.61, P < 0.001) were associated with a lower risk of EIM occurrence. IBD current clinical remission (OR = 2.42; P < 0.001) and smoking cessation (OR = 2.98; P < 0.001) were associated factors of EIM remission. Conversely, age at IBD diagnosis (OR = 0.98; P < 0.018) was associated with a lower risk of EIM remission., Discussion: One quarter of patients had at least 1 EIM. Beyond factors associated with the presence of EIMs, patients with IBD current clinical remission and smoking cessation are more likely to achieve EIM remission, while increasing age at IBD diagnosis is associated with decreased chance of remission., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background: Little is known about the prognosis of colorectal cancer associated with inflammatory bowel disease (CRC-IBD) in a real-world cohort in France., Methods: We conducted a retrospective observational study including all patients presenting CRC-IBD in a French tertiary center., Results: Among 6510 patients, the rate of CRC was 0.8% with a median delay of 19.5 years after IBD diagnosis (median age 46 years, ulcerative colitis 59%, initially localized tumor 69%). There was a previous exposure to immunosuppressants (IS) in 57% and anti-TNF in 29% of the cases. A RAS mutation was observed in only 13% of metastatic patients. OS of the whole cohort was 45 months. OS and PFS of synchronous metastatic patients was 20.4 months and 8.5 months respectively. Among the patients with localized tumor those previously exposed to IS had a better PFS (39 months vs 23 months; p = 0.05) and OS (74 vs 44 months; p = 0.03). The IBD relapse rate was 4%. No unexpected chemotherapy side-effect was observed CONCLUSIONS: OS of CRC-IBD is poor in metastatic patients although IBD is not associated with under-exposure or increased toxicity to chemotherapy. Previous IS exposure may be associated with a better prognosis., Competing Interests: Conflict of interest MA received grant supports from Innate Pharma, Janssen, Takeda, Genentech/Roche, and honoraria for teaching activities or consultancy from Abbvie, Amgen, Biogen, Boehringer-Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Ferring, Genentech, Gilead, IQVIA, Janssen, Novartis, Pfizer, Roche, Takeda, Tillots. T.A. presented conferences for Shire, Ipsen, Amgen, BMS, Servier, Pfizer, Roche Sanofi and meeting grants for Ipsen, Novartis, Roche and Hospira. He also obtained research grant from Novartis and Innate Pharma. N.H. received honoraria for consultancy from Janssen and Takeda. M.L.T.M. received honoraria from Abbvie and Janssen. J.M.G. has been a speaker and/advisory board member for Abbvie, Amgen, Celltrion, Takeda, Janssen and Sanofi Genzyme. N.L. has been a speaker for Sanofi. J.L.C., J.L., M.A., L.M., C.B., N.A., B.P., and H.C. have no conflict of interest to declare., (Copyright © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Patients with inflammatory bowel disease (IBD) may have a modified immune response to SARS-CoV-2. The objectives were to evaluate the prevalence of COVID-19 in patients treated with infliximab or vedolizumab, to analyze the factors associated with the infection, the impact of treatments and trough levels., Methods: Patients with IBD treated with intravenous biologics in 14 French centers were included between March and June 2020 and followed-up for 6 months. Blood samples were collected for serologies and trough levels. The analysis of factors associated with COVID-19 was conducted in a matched 1:1 case-control sub-study with positive patients., Results: In total, 1026 patients were included (74.9% infliximab). Over the follow-up period, 420 patients reported the occurrence of COVID-19 symptoms; 342 had been tested of whom 18 were positive. At the end of follow-up, 38 patients had a positive serology. Considering both nasal tests and serologies together, 46 patients (4.5%) had been infected. The risk of COVID-19 was related neither to the use of treatments (whatever the trough levels) nor to disease activity. Infections were more frequent when using public transport or living in flats in urban areas., Conclusions: The prevalence rate of COVID-19 in this IBD population treated with intravenous infliximab or vedolizumab was the same as the one in the French population before the start of the vaccination campaign. The risk was increased by urban living and was not influenced by disease activity or biologics. Sanitary barrier measures remain the best way to protect against SARS-CoV-2 in patients with IBD in biological therapy., Competing Interests: SN declares counseling, boards, transports or fees from Abbvie, Biogen, HAC-pharma, Janssen, MSD, Novartis, Pfizer, Takeda, Tillots, BMS, Amgen, Galapagos and Fresenius. Prof. Bouguen received lecture fees from Abbvie, Ferring, MSD, Takeda and Pfizer and consultant fees from Takeda, Janssen. MA reports consulting or lecture fees from AbbVie, Amgen, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Ferring, Genentech, Gilead, IQVIA, Janssen, Novartis, Pfizer, Roche, Takeda, and Tillots; and grant support from Innate Pharma, Janssen, Takeda, and Genentech/Roche. MS has received lecture or consulting fees from Abbvie, Ferring, Amgen, Celltrion, Janssen, Ferring, Takeda and Tillotts. LC received board and lecture fees from Abbvie, Janssen, Pfizer, Takeda, Amgen. CR has received payment for lectures from Abbvie, Biogen and Galapagos. PB has received payment for lectures from Abbvie, Pfizer, Tillotts, Fresenius Kabi and Gilead. DL declares counseling, boards, transports or fees from Abbvie, Biogaran, Biogen, Ferring, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, Prometheus, Roche, Takeda. LP-B has served as a consultant for Abbvie, Alimentiv, Alma Bio Therapeutics, Amgen, Applied Molecular Transport, Arena, Biogen, BMS, Celltrion, CONNECT Biopharm, Cytoki Pharma, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer Bio, GSK, HAC-Pharma, IAG Image Analysis, Index Pharmaceuticals, Inotrem, Janssen, Lilly, Medac, Mopac, Morphic, MSD, Norgine, Novartis, OM Pharma, ONO Pharma, OSE Immunotherapeutics, Pandion Therapeutics, Par’Immune, Pfizer, Prometheus, Protagonist, Roche, Sandoz, Takeda, Theravance, Thermo Fisher, Tigenix, Tillots, Viatris, Vifor, Ysopia, Abivax; has received payment for lectures from Galapagos, AbbVie, Janssen, Genentech, Ferring, Tillots, Celltrion, Takeda, Pfizer, Sandoz, Biogen, MSD, Amgen, Vifor, Arena, Lilly, Gilead, Viatris, Medac, Sanofi; reports grant support from Takeda, Fresenius Kabi, Celltrion; has received meeting support fees from Galapagos, AbbVie, Janssen, Genentech, Ferring, Tillots, Celltrion, Takeda, Pfizer, Gossamer Bio, Sandoz, MSD, Amgen, Lilly, Gilead, Thermo Fisher, Medac, CONNECT Biopharm. AM has received payment for lectures from Galapagos. CT-P has reveived lecture fees from Ferring, Janssen, Mayoly spindler, Norgine, Abbvie, MSD, and Takeda. AB declares lecture or consulting fees from Abbvie, Amgen, Celltrion, Ferring, Fresenius Kabi, Galapagos, Gilead, Janssen, MSD, OSE Immunotherapeutics, Pfizer, Roche, Takeda, and Tillotts. CLB has served as a consultant for Abbvie, Janssen and Gilead; has received payment for lectures from Abbvie, Amgen, Celltrion, Ferring, Fresenius Kabi, Galapagos, Janssen, Lilly, MSD, Pfizer, and Takeda; reports grant support from Abbvie and Takeda; has received meeting support fees from Abbvie, Ferring, Fresenius Kabi, Galapagos, Janssen, Lilly, Pfizer, Sandoz, and Takeda. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lelong, Josien, Coste-Burel, Rimbert, Bressollette-Bodin, Nancey, Bouguen, Allez, Serrero, Caillo, Rouillon, Blanc, Laharie, Olivier, Peyrin-Biroulet, Dib, De Maissin, Montuclard, Trang-Poisson, Vavasseur, Gallot, Berthome, Braudeau, Chevreuil, Bourreille and Le Berre.)

Background: The objective of this non-interventional, observational prospective cohort study (CONNECT-IBD) was to assess the use of CT-P13 (Inflectra®) in the treatment of patients with Crohn's disease (CD) and ulcerative colitis (UC) in the context of treatment with reference infliximab (IFX; Remicade®)., Methods: Patients (recruited April 2015 to October 2018) at 150 sites across 13 European countries were followed for up to 2 years. Primary outcomes were safety, population characteristics, and drug utilization patterns. Secondary outcomes included clinical assessment of disease activity. Data were analyzed descriptively., Results: Overall, 2543 patients (CD, n  = 1676; UC, n  = 867) were included. In the CT-P13 cohort ( n  = 1522), median disease duration was 63 (0-579) months and 30% of patients were IFX naïve; median duration of prior IFX treatment was 5 months. During the observation period, median duration of drug exposure was 14 (0-28) months. 41% of patients reported 912 all-causality treatment-emergent adverse events (TEAEs); 24% experienced treatment-related TEAEs. Most TEAEs were of mild-to-moderate severity. Treatment-emergent serious adverse events were reported by 17% of patients., Conclusion: Safety information for CT-P13 in this large study was consistent with the known safety profile for IFX and did not alter the established benefit-risk profile of CT-P13.

Background and Aim: Pneumocystis jirovecii pneumonia [PJP] is a very rare, potentially life-threatening pulmonary fungal infection that occurs in immunocompromised individuals including patients with inflammatory bowel disease [IBD]. Our aim was to describe immunosuppressive treatment exposure as well as the outcome in IBD patients with PJP., Methods: PJP cases were retrospectively collected through the COllaborative Network For Exceptionally Rare case reports of the European Crohn's and Colitis Organisation. Clinical data were provided through a case report form., Results: In all, 18 PJP episodes were reported in 17 IBD patients [10 ulcerative colitis and seven Crohn's disease]. The median age at PJP diagnosis was 55 years (interquartile range [IQR], 40-68 years]. Two PJP [11.1%] occurred in patients on triple immunosuppression, 10 patients [55.6%] had double immunosuppressive treatment, four patients [22.2%] had monotherapy and two PJP occurred in absence of immunosuppressive treatment [one in a human immunodeficiency virus patient and one in a patient with a history of autologous stem cell transplantation]. Immunosuppressive therapies included steroids [n = 12], thiopurines [n = 10], infliximab [n = 4], ciclosporin [n = 2], methotrexate [n = 1], and tacrolimus [n = 1]. None of the patients diagnosed with PJP had received prophylaxis. All patients were treated by trimethoprim/sulphamethoxazole or atovaquone and an intensive care unit [ICU] stay was required in seven cases. Two patients [aged 71 and 32 years] died, and one patient had a recurrent episode 16 months after initial treatment. Evolution was favourable for the others., Conclusion: This case series reporting potentially fatal PJP highlights the need for adjusted prophylactic therapy in patients with IBD on immunosuppressive therapy., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Lympho-epithelial interactions between intestinal T resident memory cells (Trm) and the epithelium have been associated with inflammatory bowel disease (IBD) activity. We developed ex vivo autologous organoid-mucosal T cell cocultures to functionally assess lymphoepithelial interactions in Crohn's Disease (CD) patients compared to controls. We demonstrate the direct epithelial cell death induced by autologous mucosal T cells in CD patients but not in controls. These findings were positively correlated with T cell infiltration of the organoids. This potential was inhibited by limiting lympho-epithelial interactions through CD103 and NKG2D blocking antibodies. These data directly demonstrate for the first time the direct deleterious effect of mucosal T cells on the epithelium of CD patients. Such ex-vivo models are promising techniques to unravel the pathophysiology of these diseases and the potential mode of action of current and future therapies., Competing Interests: MA received grant supports from Innate Pharma, Janssen, Takeda, Genentech/Roche, and honoraria for teaching activities or consultancy from Abbvie, Amgen, Biogen, Boehringer-Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Ferring, Genentech, Gilead, IQVIA, Janssen, Novartis, Pfizer, Roche, Takeda, Tillots. NH received honorarium for consultancy from Janssen and Takeda. M-LT-M received honoraria from Abbvie and Janssen. J-MG has been a speaker and/advisory board member for Abbvie, Amgen, Celltrion, Takeda, Janssen and Sanofi Genzyme. SH, JB, HB, KP, LC, MB, VC, BG, CG, DH, JB, HC, LM, CB, AT and LLB have no conflict of interest to declare. MN, JM are employed by Genentech and CB by Institut Roche. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest., (Copyright © 2022 Hammoudi, Hamoudi, Bonnereau, Bottois, Pérez, Bezault, Hassid, Chardiny, Grand, Gergaud, Bonnet, Chedouba, Tran Minh, Gornet, Baudry, Corte, Maggiori, Toubert, McBride, Brochier, Neighbors, Le Bourhis and Allez.)

Background & Aims: End points to determine the efficacy and safety of medical therapies for Crohn's disease (CD) and ulcerative colitis (UC) are evolving. Given the heterogeneity in current outcome measures, harmonizing end points in a core outcome set for randomized controlled trials is a priority for drug development in inflammatory bowel disease., Methods: Candidate outcome domains and outcome measures were generated from systematic literature reviews and patient engagement surveys and interviews. An iterative Delphi process was conducted to establish consensus: panelists anonymously voted on items using a 9-point Likert scale, and feedback was incorporated between rounds to refine statements. Consensus meetings were held to ratify the outcome domains and core outcome measures. Stakeholders were recruited internationally, and included gastroenterologists, colorectal surgeons, methodologists, and clinical trialists., Results: A total of 235 patients and 53 experts participated. Patient-reported outcomes, quality of life, endoscopy, biomarkers, and safety were considered core domains; histopathology was an additional domain for UC. In CD, there was consensus to use the 2-item patient-reported outcome (ie, abdominal pain and stool frequency), Crohn's Disease Activity Index, Simple Endoscopic Score for Crohn's Disease, C-reactive protein, fecal calprotectin, and co-primary end points of symptomatic remission and endoscopic response. In UC, there was consensus to use the 9-point Mayo Clinic Score, fecal urgency, Robarts Histopathology Index or Geboes Score, fecal calprotectin, and a composite primary end point including both symptomatic and endoscopic remission. Safety outcomes should be reported using the Medical Dictionary for Regulatory Activities., Conclusions: This multidisciplinary collaboration involving patients and clinical experts has produced the first core outcome set that can be applied to randomized controlled trials of CD and UC., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Inflammatory bowel diseases (IBDs) are characterized by chronic inflammation and tissue damages in limited segments of the digestive tract. Pathogenesis in the tissue and mucosal inflammation probably differs according to disease location. Our aim was to further analyze transcriptomic profiles in different locations of IBD, differentiating ulcerative colitis (UC), colonic Crohn's disease (CD), ileal CD, and pouchitis, with respect to normal colonic and ileal mucosa. We thus performed a meta-analysis focusing on specific transcriptomic signatures of ileal and colonic diseases., Methods: We identified 5 cohorts with available transcriptomic data in ileal or colonic samples from active IBD and non-IBD control samples. The meta-analysis was performed on 1047 samples. In each cohort separately, we compared gene expression in CD ileitis and normal ileum; in CD colitis, UC, and normal colon; and finally in pouchitis and normal ileum., Results: We identified specific markers of ileal (FOLH1, CA2) and colonic (REG3A) inflammation and showed that, with disease, some cells from the ileum start to express colonic markers. We confirmed by immunohistochemistry that these markers were specifically present in ileal or colonic diseases. We highlighted that, overall, colonic CD resembles UC and is distinct from ileal CD, which is in turn closer to pouchitis., Conclusions: We demonstrated that ileal and colonic diseases exhibit specific signatures, independent of their initial clinical classification. This supports molecular, rather than clinical, disease stratification, and may be used to design drugs specifically targeting ileal or colonic diseases., (© 2021 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Extraintestinal manifestations occur frequently in patients with inflammatory bowel disease (IBD) and remain a diagnostic and therapeutic challenge. The aim of the Endpoints for Extraintestinal Manifestations in Inflammatory Bowel Disease Trials (EXTRA) initiative was to achieve international expert consensus on how to assess these manifestations in IBD trials. A systematic literature review was done to identify methods to diagnose extraintestinal manifestations in patients with IBD and measure treatment outcomes. A consensus meeting involving a panel of 41 attendees, including gastroenterologists and referral specialists, was held on March 31, 2021, as part of an International Organization for the Study of Inflammatory Bowel Diseases initiative. The panel agreed that a specialist's expertise is needed to confirm the diagnosis of extraintestinal manifestations before the inclusion of a patient in IBD trials, except for axial spondyloarthritis, for which typical symptoms and MRI can be sufficient. Easy-to-measure endpoints were identified to assess the response of extraintestinal manifestations to treatment without needing specialist involvement. For uveitis, peripheral spondyloarthritis, and arthralgia, endpoint measurements need specialist expertise. The timing of endpoint measurements was discussed for individual extraintestinal manifestations. The EXTRA consensus proposes guidelines on how to thoroughly evaluate extraintestinal manifestations within IBD trials, and recommends that these guidelines are implemented in future trials to enable prospective assessment of these manifestations and comparison between studies., Competing Interests: Declaration of interests LGu reports consulting fees from AbbVie. RP reports consulting fees from AbbVie, Abbott, Alimentiv (formerly Robarts Clinical Trials), Amgen, Arena Pharmaceuticals, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly, Ferring, Galapagos, Genentech, Gilead Sciences, GlaxoSmithKline, Janssen, Merck, Mylan, Oppilan Pandion, Pharma, Pandion Pharma, Pfizer, Progenity, Protagonist Therapeutics, Roche, Satisfai Health, Sandoz, Schering-Plough, Shire, Sublimity Therapeutics, Theravance Biopharma, Union Chimique Belge, and Takeda Pharmaceuticals; and research support from AbbVie, Ferring, Janssen, Pfizer, and Takeda. WJS reports research grants from AbbVie, Abivax, Arena Pharmaceuticals, Boehringer Ingelheim, Celgene, Genentech, Gilead Sciences, GlaxoSmithKline, Janssen, Lilly, Pfizer, Prometheus Biosciences, Seres Therapeutics, Shire, Takeda, and Theravance Biopharma; consulting fees from AbbVie, Abivax, Admirx, Alfasigma, Alimentiv Alivio Therapeutics, Allakos, Amgen, Applied Molecular Transport, Arena Pharmaceuticals, Bausch Health (Salix), Beigene, Bellatrix Pharmaceuticals, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Myers Squibb, Celgene, Celltrion, Cellularity, Cosmo Pharmaceuticals, Escalier Biosciences, Equillium, Forbion, Genentech/Roche, Gilead Sciences, Glenmark Pharmaceuticals, Gossamer Bio, Immunic (Vital Therapies), Index Pharmaceuticals, Intact Therapeutics, Janssen, Kyverna Therapeutics, Landos Biopharma, Lilly, Oppilan Pharma, Otsuka, Pandion Therapeutics, Pfizer, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonists Therapeutics, Provention Bio, Reistone Biopharma, Seres Therapeutics, Shanghai Pharma Biotherapeutics, Shire, Shoreline Biosciences, Sublimity Therapeutics, Surrozen, Takeda, Theravance Biopharma, Thetis Pharmaceuticals, Tillotts Pharma, UCB, Vendata Biosciences, Ventyx Biosciences, Vimalan Biosciences, Vivelix Pharmaceuticals, Vivreon Biosciences, and Zealand Pharma; and stock or stock options from Allakos, BeiGene, Gossamer Bio, Oppilan Pharma, Prometheus Biosciences, Prometheus Laboratories, Progenity, Shoreline Biosciences, Ventyx Biosciences, Vimalan Biosciences, and Vivreon Biosciences. MAl has served as a speaker, consultant, and advisory board member for Amgen, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Ferring, Genentech IQVIA, Janssen, Novartis, Pfizer, Roche, Takeda, and Tillotts. ANA has served as an advisory board member for AbbVie, Gilead Sciences, Sun Pharma, and Ikena Therapeutics, and is supported by research funding from the Chleck Family Foundation, Crohn's and Colitis Foundation, and the National Institutes of Health. PGK reports speaking and consultancy honoraria from AbbVie, Janssen, Ferring, Pfizer, Takeda, and Novartis, and scientific grants from Pfizer and Takeda. IEK has served as an advisory board member for AbbVie, Astelas, Genesis, Janssen, Merck Sharp & Dohme, Pharmacosmos, Pfizer, Shire, and Takeda; as a speaker for AbbVie, Astelas, Genesis, Janssen, Merck Sharp & Dohme, and Takeda; and has received research support from AbbVie, Ferring, and Vifor Pharma. PLL has served as a speaker and advisory board member for AbbVie, Amgen, Arena Pharmaceuticals, Fresenius Kabi, Genetech, Gilead Sciences, Janssen, Merck, Mylan, Pharmacosmos, Pfizer, Roche, Takeda, Tillots, and Viatris; and has received unrestricted research grants from AbbVie, Takeda, and Pfizer. JOL reports honoraria for developing and delivering the Cornerstones Health Best of DDW program; funding from AbbVie, Celgene, Gilead Sciences, Janssen, Pfizer, Takeda, and Tillots; additional research support from AbbVie, Gilead Sciences, Pfizer, Shire, and Takeda; consultancy fees from AbbVie, Allergan (Warner Chilcott), Atlantic Healthcare, Bristol Myers Squibb, Celgene, Celtrion, Ferring, Gilead Sciences, GlaxoSmithKline, Janssen, Lilly, Merck Sharp & Dohme, Napp, Norgine, Pfizer, Shire, Takeda, and Vifor Pharma, and speaking fees and travel support from AbbVie, Allergan (Warner Chilcott), Ferring, Janssen, Merck Sharp & Dohme, Napp, Norgine, Pfizer, Shire, Tillotts, and Takeda. FM has served as a speaker for, and has received honoraria from, AbbVie, Biogen, Falk, Ferring, Hospira, Janssen, Laboratorios Vitoria, Lilly, Merck Sharp & Dohme, Pfizer, Takeda, Sandoz, UCB, and Vifor Pharma. GJM has served as advisory board member for AbbVie, Celgene, Celtrion, Ferring, Genesis, Hospira, Janssen, Millennium Pharmaceuticals, Merck Sharp & Dohme, Mylan, Pharmacosmos, Pfizer, Takeda, and Vianex; has served as a speaker for AbbVie, Angelini, Falk Pharma, Ferring, Galenica, Cenesis, Hospira, Janssen, Merck Sharp & Dohme, Omega Pharma, Takeda, and Vianex; has served as a consultant for Merck Sharp & Dohme and Takeda; and has received research support from AbbVie, Galenica, Genesis, Menarini Group, and Merck Sharp & Dohme. SCN reports research grants and speaker honoraria from Takeda, Ferring, AbbVie, Janssen, and Tillotts. JP has received research grants from AbbVie and Pfizer; speaker's fees from AbbVie, Ferring, Janssen, Pfizer, and Takeda; and has been a consultant for AbbVie, Arena Pharmaceuticals, Boehringer Ingelheim, Celgene, Celltrion, Ferring, Genentech, GlaxoSmithKline, Janssen, Origo, Pandion, Pfizer, Progenity, Alimentiv (formerly Robarts Clinical Trials), Roche, Takeda, Theravance, and Wassermann. GR has consulted for AbbVie, Augurix, Bristol Myers Squibb, Boehringer, Calypso, Celgene, Falk, Ferring, Fisher, Genentech, Gilead Sciences, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Phadia, Roche, UCB, Takeda, Tillotts, Vifor Pharma, Vital Solutions, and Zeller; has received speaker's honoraria from AstraZeneca, AbbVie, Falk, Janssen, Merck Sharp & Dohme, Pfizer, Phadia, Takeda, Tillotts, UCB, Vifor Pharma, and Zeller; and has received educational grants and research grants from AbbVie, Ardeypharm, Augurix, Calypso, FALK, Flamentera, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Takeda, Tillotts, UCB, and Zeller. FS has served as a speaker and consultant for AbbVie, Amgen, Ferring, Janssen, Pfizer, Sandoz, Takeda, and UCB. AD has served as a speaker, consultant, and advisory board member for Merck Sharp & Dohme, AbbVie, Janssen, Roche/Genentech, Ferring, Tillotts, Vifor Pharma, Pharmacosmos, Pfizer, Celltrion, Takeda, Boehringer Ingelheim, Amgen, Sandoz, Bristol Myers Squibb/Celgene, Otsuka, Biogen, Gilead/Galapagos, Fresenius Kabi, and Arena Pharmaceuticals. BES reports consulting fees from 4D Pharma, AbbVie, Allergan, Amgen, Arena Pharmaceuticals, AstraZeneca, Boehringer Ingelheim, Boston Pharmaceuticals, Capella Biosciences, Celgene, Celltrion Healthcare, EnGene, Ferring, Genentech, Gilead Sciences, Hoffmann-La Roche, Immunic, Ironwood Pharmaceuticals, Janssen, Lilly, Lyndra, MedImmune, Morphic Therapeutic, Oppilan Pharma, OSE Immunotherapeutics, Otsuka, Palatin Technologies, Pfizer, Progenity, Prometheus Laboratories, RedHill Biopharma, Rheos Medicines, Seres Therapeutics, Shire, Synergy Pharmaceuticals, Takeda, Target PharmaSolutions, Theravance Biopharma R&D, TiGenix, and Vivelix Pharmaceuticals; honoraria for speaking in continuing medical education programmes from Takeda, Janssen, Lilly, Gilead Sciences, Pfizer, and Genentech; and research funding from Celgene, Pfizer, Takeda, Theravance Biopharma R&D, and Janssen. SD has served as a speaker, consultant, and advisory board member for Schering-Plough, Abbott (AbbVie) Laboratories, Merck & Co, UCB Pharma, Ferring, Cellerix, Millennium Takeda, Nycomed, Pharmacosmos, Actelion, A Wasserman, Genentech, Grunenthal, Pfizer, AstraZeneca, Novo Nordisk, Cosmo Pharmaceuticals, Vifor Pharma, and Johnson & Johnson. LP-B has served as a speaker, consultant, and advisory board member for Merck, AbbVie, Janssen, Genentech, Mitsubishi, Ferring, Norgine, Tillotts, Vifor Pharma, Hospira/Pfizer, Celltrion, Takeda, Biogaran, Boehringer Ingelheim, Lilly, HAC Pharma, Index Pharmaceuticals, Amgen, Sandoz, Forward Pharma, Celgene, Biogen, Lycera, Samsung Bioepis, and Theravance. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Due to the potential role of the gut microbiota and bile acids in the pathogenesis of both inflammatory bowel disease (IBD) and sporadic colorectal cancer, we aimed to determine whether these factors were associated with colorectal cancer in IBD patients. 215 IBD patients and 51 non-IBD control subjects were enrolled from 10 French IBD centers between September 2011 and July 2018. Fecal samples were processed for bacterial 16S rRNA gene sequencing and bile acid profiling. Demographic, clinical, endoscopic, and histological outcomes were recorded. Characteristics of IBD patients included: median age: 41.6 (IQR 22); disease duration 13.2 (13.1); 47% female; 21.9% primary sclerosing cholangitis; 109 patients with Crohn's disease (CD); 106 patients with ulcerative colitis (UC). The prevalence of cancer was 2.8% (6/215: 1 CD; 5 UC), high-grade dysplasia 3.7% (8/215) and low-grade dysplasia 7.9% (17/215). Lachnospira was decreased in IBD patients with cancer, while Agathobacter was decreased and Escherichia-Shigella increased in UC patients with any neoplasia. Bile acids were not associated with cancer or neoplasia. Unsupervised clustering identified three gut microbiota clusters in IBD patients associated with bile acid composition and clinical features, including a higher risk of neoplasia in UC in two clusters when compared to the third (relative risk (RR) 4.07 (95% CI 1.6-10.3, P < .01) and 3.56 (95% CI 1.4-9.2, P < .01)). In this multicentre observational study, a limited number of taxa were associated with neoplasia and exploratory microbiota clusters co-associated with clinical features, including neoplasia risk in UC. Given the very small number of cancers, the robustness of these findings will require assessment and validation in future studies.

Background: Hydrocortisone premedication reduces the risk of antibodies to infliximab [ATIs] formation in patients receiving infliximab [IFX] therapy for inflammatory bowel disease [IBD]., Aim: We aimed to determine the safety of hydrocortisone premedication withdrawal in IBD patients with sustained clinical response on maintenance therapy with IFX., Methods: We performed an observational prospective pharmacoclinical study in a tertiary referral centre, including all consecutive IBD outpatients with no previous IFX infusion reaction and in clinical remission on maintenance IFX [alone or in combination therapy] for at least 6 months. This cohort was followed for 1 year after discontinuation of hydrocortisone premedication., Results: Among the 268 IBD outpatients, 95 patients met the inclusion criteria [mean age 38 years; 64% male; 80% Crohn's disease; 45% combination therapy]. The median IFX duration was 5 years [0.54-14] with a mean infused dose of 533 mg [200-1000] and a mean interval duration of 7.9 weeks [4-10]. None of the patients developed permanent ATIs or infusion-related reaction at 1 year. Four patients developed transient ATIs without loss of clinical response. There was no significant variation of infliximab serum trough levels [5.5 µg/mL vs 5.9 µg/mL] measured at the time of the three IFX infusions before and after hydrocortisone withdrawal. Loss of response rate to IFX was 18% at 1 year., Conclusions: Hydrocortisone discontinuation is safe in IBD patients with sustained clinical remission on maintenance therapy with IFX. Our data suggest that routine premedication with hydrocortisone is unnecessary in patients in prolonged remission under IFX maintenance therapy., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Aim: The inflammatory bowel disease [IBD]-disk is a 10-item self-questionnaire that is used to assess IBD-related disability. The aim of the present study was to evaluate this tool in the assessment of IBD daily-life burden., Methods: A 1-week cross-sectional study was conducted in 42 centres affiliated in France and Belgium. Patients were asked to complete the IBD-disk [best score: 0, worst score: 100] and a visual analogue scale [VAS] of IBD daily-life burden [best score: 0, worst score: 10]. Analyses included internal consistency, correlation analysis, and diagnostic performance assessment., Results: Among the 2011 IBD outpatients who responded to the survey [67.8% of the patients had Crohn's disease], 49.9% were in clinical remission. The IBD-disk completion rate was 73.8%. The final analysis was conducted in this population [n = 1455 patients]. The mean IBD-disk score and IBD daily-life burden VAS were 39.0 ± 23.2 and 5.2 ± 2.9, respectively. The IBD-disk score was well correlated with the IBD daily-life burden VAS [r = 0.67; p <0.001]. At an optimal IBD-disk cut-off of 40, the area under the receiver operating characteristic curve [AUROC] for high IBD daily-life burden [VAS >5] was 0.81 (95% confidence interval [CI]: 0.79-0.83; p <0.001)., Conclusions: In a large cohort of patients, the IBD-disk score was well correlated with IBD daily-life burden, and it could be used in clinical practice., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The burden of inflammatory bowel disease (IBD) is rising worldwide. The goal of IBD treatment is to achieve clinical and endoscopic remission but also prevent disability., Aims: To identify the predictive factors of disability in a large population of patients with IBD., Patients and Methods: We conducted a cross-sectional survey in 42 tertiary centres in France and Belgium. A self-administered questionnaire was designed to explore patients and their IBD characteristics. IBD-disk is a validated tool to measure disability in patients with IBD. The IBD-disk score was then calculated for each patient. Based on a previous study, an overall IBD-disk score ≥40 was associated with moderate-to-severe disability., Results: Among the 2011 patients, 1700 were analysed, including 746 (44%) in self-reported clinical remission and 752 (44.2%) declaring clinical activity. The patient global assessment of global remission was missing in 200 (11.8%) of 1700 patients. Moderate-to-severe disability was significantly increased in patients with BMI >25 kg/m 2 (OR = 1.66; 95% CI [1.29-2.14]), in those having perception of need for a psychotherapist (OR = 2.24; 95% CI [1.79-3.05]) and social worker (OR = 1.54; 95% CI [1.08-2.21]). Conversely, male gender (OR = 0.83; 95% CI [0.69-0.99]), ulcerative colitis (OR = 0.69; 95% CI [0.53-0.92]), self-reported clinical remission (OR = 0.59; 95% CI [0.46-0.77]) and employed or student occupational status (OR = 0.69; 95% CI [0.52-0.92]) were inversely correlated with disability. Overall, 257 (34.5%) patients who declared being in clinical remission had disability., Conclusion: Determinants of IBD-related disability include IBD-related factors but also psychological and social factors. This highlights the importance of a multidisciplinary team in the management of patients with IBD., (© 2021 John Wiley & Sons Ltd.)

Background: Patients' experience with healthcare professionals could influence their clinical outcomes., Aims: To assess inflammatory bowel disease (IBD) patients' experience with their disease, their treatment and their relationship with their physician., Methods: A one-week cross-sectional study was conducted in 42 IBD centres. 2011 consecutive outpatients with IBD completed an anonymous self-report questionnaire assessing their experience with and knowledge of IBD., Results: A quantitative assessment of the doctor-patient relationship revealed that patients' knowledge of IBD and IBD treatment ranged from 7.4 to 8.3 out of 10. In addition to IBD physicians, other sources of information about IBD and current treatment mainly included the internet (80% and 63%, respectively) and general practitioners (61% and 54%). Knowledge about education programmes (28%) was poor, resulting in a lack of willingness to further use these resources (25%). Concerns about IBD treatment were raised in 76% of patients, mostly related to the fear of adverse events (47%) and a lack of efficacy (33%). The need of alternative healthcare professionals was reported by 89% of the sample., Conclusion: In a large cohort of patients, we highlighted gaps in the management of patients with IBD regarding the need for higher-quality information and the implementation of alternative healthcare professionals., (Copyright © 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Better patient knowledge on inflammatory bowel disease [IBD] could improve outcome and quality of life. The aim of this study was to assess if an education programme improves IBD patients' skills as regards their disease., Methods: The GETAID group conducted a prospective multicentre randomised controlled study. IBD patients were included at diagnosis, or after a significant event in the disease course. Patients were randomised between 'educated' or control groups for 6 months. Education was performed by trained health care professionals. A psycho-pedagogic score [ECIPE] was evaluated by a 'blinded' physician at baseline and after 6 and 12 months [M6 and M12]. The primary endpoint was the increase of ECIPE score at M6 of more than 20%., Results: A total of 263 patients were included in 19 centres (male:40%; median age:30.8; Crohn's disease [CD]:73%). Of these, 133 patients were randomised into the educated group and 130 into the control group. The median relative increase in ECIPE score at M6 was higher in the educated group as compared with the control group (16.7% [0-42.1%] vs 7% [0-18.8%], respectively, p = 0.0008). The primary endpoint was met in 46% vs 24% of the patients in the educated and control groups, respectively [p = 0.0003]. A total of 92 patients met the primary endpoint. In multivariate analysis, predictors of an increase of at least 20% of the ECIPE score were randomisation in the educated group (odds ratio [OR] = 2.59) and no previous surgery [OR = 1.92]., Conclusions: These findings support the set-up of education programmes in centres involved in the management of IBD patients., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Patients who receive infliximab (IFX) combined with a thiopurine, for inflammatory bowel disease, have a better clinical response and less frequent immunization towards IFX than those treated with IFX alone. The benefits of combination therapy must be weighed against the risks of infection and cancer. We studied the association between the duration of combination therapy and the risk of treatment failure by two year from initiation., Methods: Participants had Crohn's disease or ulcerative colitis and were in clinical and biological remission, 6 months after initiation of combination therapy. The risk of subsequent treatment failure (i.e., undetectable trough IFX levels and/or clinical relapse followed by surgical treatment or switch of maintenance treatment) was estimated using Kaplan-Meier method and adjusted Hazard Ratios (aHRs), in patients whohadreceived 6 to 11 months vs. 12 months or more of combination therapy. We performed a similar analysis in which the follow-up was started at discontinuation of the immunosuppressant., Results: Among 139 patients (48% women; median age 31.1), with a median follow-up of 18.9 months, we observed 26 treatment failures (including 15 patients with undetectable trough IFX levels). After adjustment for gender and type of immunomodulator, a shorter duration of combination therapy was not associated with a higher risk of treatment failure (aHR=0.42; 95% confidence interval (95%CI): 0.13-1.40; p=0.16). When the follow-up was started at discontinuation of the immunosuppressant, a combination therapy of 6-11 months was associated with a numerically lower risk of treatment failure as compared with a longer combination therapy (HR=0.12; 95%CI: 0.01-1.05; p=0.055)., Conclusion: Our results do not show any benefit for continuation of combination therapy for more than 12 months after achieving clinical remission in IBD patients., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Background: The prevalence of inflammatory bowel diseases (IBD) is high in women of childbearing age. Achieving clinical remission from conception to delivery using current medications is a major issue in IBD., Aims: To assess maternal and neonatal complications and management of vedolizumab or ustekinumab) in pregnant women with IBD receiving these agents., Methods: We performed a retrospective cohort study among GETAID centres including women with IBD who received ustekinumab or vedolizumab during pregnancy or within the 2 months before conception and compared outcomes to women exposed to anti-TNF treatment during pregnancy., Results: Seventy-three pregnancies in 68 women with IBD were analysed: 29 on ustekinumab resulting in 26 (90%) live births, two (7%) spontaneous abortions and one (3%) elective termination; 44 on vedolizumab resulting in 38 (86%) live births, five (11%) spontaneous abortions and one (3%) medical interruption. The control group included 88 pregnancies exposed to anti-TNF in 76 women with IBD. The median age at conception, the proportion of women who smoked or in clinical activity at conception was comparable between groups. Only the proportion of patients exposed to >2 anti-TNF agents was significantly increased among the ustekinumab and vedolizumab groups compared to control group (22% and 10% vs 3%, P < 0.005). Rates of prematurity, spontaneous abortion, congenital malformations and maternal complications were comparable between groups., Conclusion: We report 73 pregnancies in patients receiving vedolizumab or ustekinumab without a negative signal on maternal or neonatal outcomes. Further prospective studies are needed on the outcomes of pregnancies with new biologic drugs., (© 2020 John Wiley & Sons Ltd.)

The management of IBD has been highly affected in the context of the COVID-19 pandemic, with restriction of hospitalisations and unprecedented redeployment of health care resources. Hospital admissions of IBD patients should be limited to reduce the risks of coronavirus transmission. However, delaying hospitalisation of IBD patients with severe or complicated disease may increase the risk of poor outcomes. Delaying surgery in some cases may increase the risk of disease progression, postoperative morbidity, and disease complications. IBD patients who are infected with SARS-CoV-2 may have a higher risk of poor outcomes than the general population, potentially related to concomitant medications, especially corticosteroids. There is no evidence today that IBD patients with COVID-19 have worse outcomes if they receive immunosuppressant medications including thiopurines, biologics, and novel small molecules. This article summarises recommendations by the international membership of IOIBD regarding hospitalisations of IBD patients, either for active or complicated IBD or for severe COVID-19, and for management of IBD patients according to SARS-CoV-2 infectious status., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Whether therapeutic drug monitoring (TDM) of infliximab should be implemented in daily practice is an ongoing controversy., Aims: To assess the real-world use of TDM in an observational multicentre cohort study with consecutive patients with inflammatory bowel disease (IBD) treated with CT-P13., Methods: Between September 2015 and December 2016, 364 patients with IBD were treated with CT-P13 in 13 gastroenterology departments and were followed up for 54 weeks. Disease activity, CT-P13 trough concentration and anti-CT-P13 antibody (ACA) were recorded., Results: Steroid-free clinical remission rates at week 54 were 67.0% and 56.4% in patients with CD and UC, respectively. CT-P13 trough concentrations were measured in 70.7% of the patients. The mean CT-P13 trough concentration was 4.2±4.3μg/mL. The presence of ACA was observed in 53 (15.9%) patients. CT-P13 trough concentration was collected in a proactive approach in 62.8% of cases and in a reactive approach in 37.2%. Among patients who submitted to TDM, CT-P13 therapy was optimized in 88.7% of the reactive group and in 22.5% of the proactive group (P<0.001)., Conclusion: In a real-world cohort of patients with IBD treated with CT-P13, more than two-thirds of the patients underwent TDM. CT-P13 optimization was much less common in the proactive approach than in the reactive approach., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Inflammatory bowel disease (IBD) is characterized by uncontrolled inflammation in the gastrointestinal tract. The underlying pathobiology of IBD includes an increase in infiltrating gut-homing lymphocytes. Although lymphocyte homing is typically a tightly regulated and stepwise process involving multiple integrins and adhesion molecules expressed on endothelial cells, the distinct roles of integrin-expressing immune cells is not fully understood in the pathology of IBD. In this review, we detail the involvement of integrins expressed on specific lymphocyte subsets in the pathogenesis of IBD and discuss the current status of approved and investigational integrin-targeted therapies., (© 2019 The Authors. Medicinal Research Reviews Published by Wiley Periodicals, Inc.)

Objectives: Vedolizumab (VDZ) blocks α4β7 integrin and is licenced for the treatment of IBD. It has been associated with mild SpA-related features, including sacroiliitis and synovitis. Herein we report a series of cases demonstrating the emergence of severe SpA-associated enthesitis/osteitis following successful IBD therapy with VDZ., Methods: We evaluated 11 VDZ-treated patients with IBD across seven centres who developed severe active SpA and/or enthesopathy, with the aim of characterizing the VDZ-associated SpA or entheseal flares. Imaging features demonstrating particularly severe disease were recorded., Results: De novo SpA developed in 9 of 11 patients and flare of known SpA in 2 patients, with 4 patients requiring hospitalization due to disease severity. Available data showed that one of seven cases were HLA-B27 positive. The median time from VDZ initiation to flare was 12 weeks, with IBD well controlled in 7 of 10 patients (no data for 1 patient) at flare. Severe SpA enthesitis/osteitis was evident on MRI or US, including acute sacroiliitis (n = 5), extensive vertebral osteitis (n = 1), peri-facetal oedema (n = 1) and isolated peripheral enthesitis (n = 3). Due to arthritis severity, VDZ was discontinued in 9 of 11 patients and a change in therapy, including alternative anti-TNF, was initiated., Conclusion: Severe SpA, predominantly HLA-B27 negative, with osteitis/enthesitis may occur under successful VDZ treatment for IBD, including in subjects with prior anti-TNF therapy for intestinal disease., (© The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Complete cytoreductive surgery (CCRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) is a validated treatment in selected patients with peritoneal metastases (PM) of intestinal origin. There is an increased risk of Colorectal Cancer (CRC) and Small Bowel Adenocarcinoma (SBA) in Inflammatory Bowel Disease (IBD). The feasibility and benefit of that surgical approach in IBD patients is unknown., Methods: IBD patients with operated PM complicating CRC or SBA were extracted from a French national multicenter prospective database of patients who underwent surgery for PM in HIPEC expert centers from 1995 to 2016. IBD patients who underwent CCRS plus HIPEC were compared with a cohort of 234 patients who had the same surgery for sporadic colon cancer., Results: 14 patients (male 57%, median age 40 years, 12 Crohn's disease) with CRC (n = 7) and SBA (n = 7) were included. CCRS followed by HIPEC (oxaliplatin 72.7%) was performed in 11 cases (median peritoneal cancer index 7; range 1-30). The control group had the same characteristics except an older age at HIPEC (56.52 vs 45.74; p = 0.003). Overall survival (HR = 4.47; 90% CI, 1.91 to 10.49), Relapse Free Survival (HR = 2.31; 90% CI, 1.17 to 4.56) and Peritoneal Recurrence Free Survival (HR = 3.30; 90% CI, 1.59 to 6.85) were significantly lower in IBD patients. Six of the 11 patients presented major surgical morbidity with no impact on post-operative treatment., Conclusion: CCRS followed by HIPEC is less effective in IBD patients with resectable PM complicating CRC or SBA. More careful selection of those patients is needed., (Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Colonoscopy with pan-chromoendoscopy (CE) is superior to standard colonoscopy in detecting neoplasia in patients with IBD. Performing random biopsies in unsuspicious mucosa after CE remains controversial., Methods: Consecutive patients with IBD who underwent surveillance colonoscopy using CE were prospectively included. The standardised procedure used CE, performed targeted biopsies or endoscopic resection on suspicious lesions and then quadrant random biopsies every 10 cm. A panel of five expert pathologists reviewed histological slides with dysplasia. Logistic regression model was used to evidence the factors associated with neoplasia in any or in random biopsies., Results: 1000 colonoscopes were performed in 1000 patients (495 UC, 505 Crohn's colitis). In 82 patients, neoplasia was detected from targeted biopsies or removed lesions, and among them dysplasia was detected also by random biopsies in 7 patients. Importantly, in 12 additional patients dysplasia was only detected by random biopsies. Overall, 140 neoplastic sites were found in 94 patients, 112 (80%) from targeted biopsies or removed lesions and 28 (20%) by random biopsies. The yield of neoplasia by random biopsies only was 0.2% per-biopsy (68/31 865), 1.2% per-colonoscopy (12/1000) but 12.8% per-patient with neoplasia (12/94). Dysplasia detected by random biopsies was associated with a personal history of neoplasia, a tubular appearing colon and the presence of primary sclerosing cholangitis (PSC)., Conclusions: Despite their low yield, random biopsies should be performed in association with CE in patients with IBD with a personal history of neoplasia, concomitant PSC or a tubular colon during colonoscopy., Trial Registration Number: IRB 001508, Paris 7 University., Competing Interests: Competing interests: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background: The effectiveness of vedolizumab as a treatment for extraintestinal manifestations (EIM) is questionable due to its gut-specificity., Aim: To assess effectiveness of vedolizumab for EIM in patients with inflammatory bowel disease (IBD) in a large real-life experience cohort., Methods: Between June and December 2014, 173 patients with Crohn's disease and 121 with ulcerative colitis were treated with vedolizumab. Patients were followed until week 54. EIM activity was assessed at weeks 0, 6, 14, 22, 30 and 54 by using a 3-step scale: complete remission, partial response and no response., Results: At baseline, 49 (16.7%) patients had EIMs of which 47 had inflammatory arthralgia/arthritis, four had cutaneous lesions and two had both rheumatologic and skin EIM. At week 54, 21 (44.7%) patients had complete remission for inflammatory arthralgia/arthritis and three (75%) for cutaneous EIM. In multivariate analysis, complete remission of inflammatory arthralgia/arthritis was associated with clinical remission of IBD (OR = 1.89, IC95% [1.05-3.41], P = .03) and recent onset of inflammatory arthralgia/arthritis (OR = 1.99, IC95% [1.12-3.52], P = .02). During the follow-up period, 34 (13.8%) patients without any EIM at baseline, developed incident cases of inflammatory arthralgia/arthritis consisting mostly of peripheral arthralgia without evidence of arthritis and 14 (4.8%) incident cases of paradoxical skin manifestation., Conclusion: Vedolizumab therapy is commonly associated with improvement in EIM. This was associated with quiescent IBD and recent EIM. However, paradoxical skin manifestation and inflammatory arthralgia/arthritis may occur upon vedolizumab therapy., (© 2017 John Wiley & Sons Ltd.)

Introduction: Autoimmune cytopenias (AIC) including autoimmune hemolytic anemia (AIHA) and immunologic thrombocytopenia (ITP) are rare immunologic disorders, scarcely reported in inflammatory bowel diseases (IBD). We conducted a multicentric retrospective study, including a case-control analysis, that aimed to describe the characteristics and outcomes of patients affected by AIC and IBD., Method: Forty cases were recruited from 4 IBD centers and 2 AIC tertiary centers. Controls were recruited from the MICISTA registry., Results: From the MICISTA registry, incidences were estimated at 4.1/100,000 patient-years and 12.5/100,000 patient-years after IBD diagnosis for AIHA and ITP, respectively. All AIHA patients (n=14) had colonic involvement (13/14 with UC), whereas CD (52%) and UC (48%) diagnoses were evenly distributed among ITP patients. Compared to control IBD patients, cases were characterized by a higher frequency of extra-intestinal manifestations (37.5% vs 17%, p<0.001) and by the presence of IBD severity's hallmark. AIHA and IBD ran mainly in parallel, and 12 out of 14 AIHA were warm AIHA. In isolated cases, rituximab and infliximab were efficient to treat IBD and AIC, respectively. IBD surgery may induce AIC remission in some cases., Conclusion: Although low, incidence of AIC appears higher in IBD patients compared to the general population. The association seems to be mainly non-fortuitous, especially for colitis-associated AIHA., (Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background & Aims: Phase 3 trials have shown the efficacy of vedolizumab, which binds to integrin α4β7, in patients with Crohn's disease (CD) or ulcerative colitis (UC). We investigated the effectiveness and safety of vedolizumab in patients who failed anti-tumor necrosis factor therapy., Methods: From June through December 2014, there were 173 patients with CD and 121 patients with UC who were included in a multicenter nominative compassionate early access program granted by French regulatory agencies. This program provided patients with access to vedolizumab before it was authorized for marketing. Vedolizumab (300 mg) was administered intravenously at weeks 0, 2, and 6, and then every 8 weeks. Disease activity was assessed using the Harvey-Bradshaw Index for CD and the partial Mayo Clinic score for UC. We report results obtained after the 14-week induction phase., Results: Among the 294 patients treated with vedolizumab (mean age, 39.5 ± 14.0 y; mean disease duration, 10.8 ± 7.6 y; concomitant steroids, 44% of cases), 276 completed the induction period, however, 18 discontinued vedolizumab because of a lack of response (n = 14), infusion-related reaction (n = 2), or infections (n = 2). At week 14, 31% of patients with CD were in steroid-free clinical remission and 51% had a response; among patients with UC, 36% were in steroid-free clinical remission and 50% had a response. No deaths were reported. Severe adverse events occurred in 24 patients (8.2%), including 15 (5.1%) that led to vedolizumab discontinuation (1 case of pulmonary tuberculosis and 1 rectal adenocarcinoma)., Conclusions: In a cohort of patients with CD or UC who failed previous anti-tumor necrosis factor therapy, approximately one third of patients achieved steroid-free clinical remission after 14 weeks of induction therapy with vedolizumab. This agent had an acceptable safety profile in these patients., (Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.)

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.)

Inflammatory bowel diseases (IBD) are associated with an increased risk of gastrointestinal cancers depending on the specific type of IBD, the extent of the disease and its location. Patients with IBD and extensive colonic involvement are at increased risk of colorectal cancer whereas patients with Crohn disease have an increased risk for small-bowel and anal carcinoma. These cancers preferentially develop on sites of longstanding inflammation. In regards to colon cancer, several key pathogenic events are involved, including chromosomal instability, microsatellite instability and hypermethylation. The risk for colon cancer in IBD patients correlates with longer disease duration, presence of sclerosing cholangitis, pancolitis, family history of colorectal cancer, early onset of the disease and severity of bowel inflammation. Identification of increased colorectal cancer risk in individual IBD patients has led to formal surveillance guidelines. Conversely, although an increased risk for other types of cancer has been well identified, no specific formal screening recommendations exist. Consequently, the role of the radiologist is crucial to alert the referring gastroenterologist when a patient with IBD presents with unusual imaging findings at either computed tomography (CT) or magnetic resonance (MR) imaging. This review provides an update on demographics, molecular, clinical and histopathological features of gastrointestinal cancers in IBD patients including colorectal carcinoma, small bowel adenocarcinoma, neuroendocrine tumors and anal carcinoma, along with a special emphasis on the current role of CT and MR imaging., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background and Aims: Data on the efficacy and safety of seasonal influenza vaccines in patients with inflammatory bowel disease (IBD) remain scarce. The aim of the study was to evaluate the impact of immunosuppressive (IS) therapeutics on serological response to 2-year influenza vaccination in IBD adults., Methods: A multicentre prospective study performed in 255 IBD adults (18-64 years) receiving the trivalent influenza vaccine in the years 2009-2010 and 2010-2011. Haemagglutination inhibition (HI) titres were assessed before and 3 weeks and 6 months after vaccination., Results: At inclusion, 31 patients were receiving no IS treatment (Group A), 77 were receiving IS treatment without anti-TNF (Group B) and 117 were receiving anti-tumour necrosis factor (TNF) treatment with or without IS treatment (Group C). Three weeks after the first vaccination, rates of seroprotection were 77, 75 and 66% for strain A/H1N12007 (p = 0.35), 77, 68 and 52% for strain A/H3N2 (p = 0.014) and 97, 96 and 95% for strain B (p = 0.99) in Groups A, B and C, respectively. Seroconversion rates for A/H1N12007 (67, 64 and 54%; p = 0.28), A/H3N2 (63, 50 and 41%; p = 0.074) and strain B (63, 76 and 60%; p = 0.078) were not significantly different among treatment groups. At 6 months after vaccination, seroprotection rates were lower in Group C compared with Groups A and B. Comparable results were observed for the second year of vaccination. No impact on Harvey-Bradshaw and Mayo scores was detected., Conclusions: Influenza vaccine yielded high seroprotection rates in IBD patients. Persistence of seroprotection was lower in patients with anti-TNF treatment. ClinicalTrials.gov, number NCT01022749., (Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Inflammatory bowel diseases (IBD) are associated with an increased risk of gastrointestinal cancers and more specifically in sites affected by chronic inflammation. However, patients with IBD have also an increased risk for developing a variety of extra-intestinal cancers. In this regard, hepatobiliary cancers, such as cholangiocarcinoma, are more frequently observed in IBD patients because of a high prevalence of primary sclerosing cholangitis, which is considered as a favoring condition. Extra-intestinal lymphomas, mostly non-Hodgkin lymphomas, and skin cancers are also observed with an increased incidence in IBD patients by comparison with that in patients without IBD. This review provides an update on demographics, risk factors and clinical features of extra-intestinal malignancies, including cholangiocarcinoma, hepatocellular carcinoma and lymphoma, that occur in patients with IBD along with a special emphasis on the multidetector row computed tomography and magnetic resonance imaging features of these uncommon conditions., (Copyright © 2015 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.)

Purpose of Review: The treatment of inflammatory bowel disease (IBD) in the modern area has improved with more biological agents available. Although the efficacy of these drugs has been demonstrated, concerns about their safety profile have been raised, and new data have emerged in the past year., Recent Findings: New data regarding the safety profile of anti-TNF were published over the last year, with a better identification of patients at risk of infection, and specific recommendations for the prevention of infections. There is a mild increase in malignancy in patients receiving anti-TNF, mainly lymphoma and skin cancer, which seems mainly attributable to combination with thiopurines. Specific recommendations for management of pregnancy were published., Summary: Biological treatments are effective and safe in the treatment of IBD, provided that the recommendations for their use and monitoring are followed.

Background: The safety of anti-tumour necrosis factor (TNF) agents during pregnancy is a major concern for child-bearing women and physicians., Aim: To assess the impact of anti-TNF therapy on adverse pregnancy and foetal outcomes in women with inflammatory bowel disease (IBD)., Methods: Pregnancies occurring during anti-TNF treatment or less than 3 months after its cessation in IBD patients followed in GETAID centres were recorded from January 2009 to December 2010. Ninety-nine pregnancies in women without anti-TNF treatment were identified from the CESAME registry. We compared pregnancy and neonatal outcomes by a case-control study., Results: In the 124 IBD patients followed, 133 pregnancies were reported. At the conception time, 23% of patients had active disease. Eighty-eight per cent (n = 117) of the 133 pregnancies followed until delivery resulted in 118 liveborns (one twin pregnancy). Complications were observed in 47 (35%) women and 24 (20%) newborns. In multivariate analysis, factors associated with pregnancy complications were: current smoking (P = 0.004), a B2 (stenotic) phenotype in CD women (P = 0.004), occurrence of a flare during pregnancy (P = 0.006) and a past history of complicated pregnancy (P = 0.007). Current smoking was the only factor associated with severe (i.e. potentially lethal) pregnancy complications (P = 0.02). Having IBD for more than 10 years prior to conception was associated with newborn complications (P = 0.007). No difference was found with the control group for any of the pregnancy and neonatal outcomes., Conclusion: In our series, the safety profile of anti-TNF therapy during pregnancy and the neonatal period appears similar to control group of IBD women not treated with anti-TNF therapy., (© 2014 John Wiley & Sons Ltd.)

Reports of autoimmune diseases, including psoriasis- and dermatitis-like skin reactions with anti-tumor necrosis factor-α (TNF-α), are increasing, likely a reflection of the growing use of these agents. This paradoxical phenomenon can no longer be considered rare, with some studies providing incidence estimates of greater than 10%. This paradoxical inflammation has been reported in patients receiving treatment with anti-TNF-α agents for a variety of inflammatory conditions, including inflammatory bowel disease, psoriasis and rheumatoid arthritis and appears to be a class effect. Moreover, there have recently been reports of autoimmune arthralgia occurring in patients receiving anti-TNF-α agents. Further studies are necessary to determine the true incidence of this phenomenon and to identify those patients most likely to be at risk., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background & Aims: There is an unclear risk of colonic high-grade dysplasia (HGD) and colorectal cancer (CRC) among patients with inflammatory bowel disease (IBD) treated with immunosuppressants. We analyzed data on CRC development among patients with IBD enrolled in the observational cohort Cancers et Surrisque Associé aux Maladies Inflammatoires Intestinales En France (CESAME)., Methods: We followed and collected data from 19,486 patients with IBD (60.3% with Crohn's disease, 30.1% receiving thiopurine therapy) enrolled in CESAME from May 2004 and June 2005, and followed them until December 2007. When the study began, 2841 patients (14.6%) were characterized as having long-standing extensive colitis (ie, >10 years and involving ≥50% of the colon). Early lesions (HGD and CRC) were defined as those diagnosed within 10 years after diagnosis of IBD., Results: Thirty-seven patients developed CRC during the follow-up period, and 20 developed colorectal HGD. The standardized incidence ratios of CRC were 2.2 for all IBD patients (95% confidence interval [CI]: 1.5-3.0; P < .0001), 7.0 for patients with long-standing extensive colitis (95% CI: 4.4-10.5; P < .001), and 1.1 for patients without long-standing extensive colitis (95% CI: 0.6-1.8; P = .84). Among patients with long-standing extensive colitis, the multivariate adjusted hazard ratio for colorectal HGD and cancer was 0.28 for those who received thiopurines compared with those who never received thiopurine therapy (95% CI: 0.1-0.9; P = .03). Twenty-two patients developed early lesions; 7 of these were related to IBD, based on histologic analysis., Conclusions: Patients with IBD and long-standing extensive colitis are at increased risk for CRC, although the risk is lower among patients receiving thiopurine therapy. Patients without long-standing extensive colitis have a risk for CRC similar to that of the general population, but they can develop IBD-related lesions within 10 years after diagnosis of IBD., (Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.)

In patients suffering from reflux esophagitis, the severity of the lesions helps to predict the prognosis and adapt treatment. We herein review the data which suggest that endoscopy also has a prognostic value in inflammatory bowel disease. In the 1990s, the general opinion, based on a few studies, was that assessing endoscopic lesions was not critical for the management of inflammatory bowel disease. The more recent therapeutic strategies using less steroids but purine analogs and anti-TNF antibodies have led to a higher chance of mucosal healing (MH), and there is growing evidence that reaching healing of lesions is of good prognostic value both in ulcerative colitis and Crohn's disease. There is a lower risk of hospitalization and of surgery in patients with MH than in those without healing. There is also a (moderately) lower risk of relapse after stopping treatments in patients with MH than in those with persistent lesions. The risk of cancer (on a long-term basis) also seems be lower in patients with controlled inflammatory lesions than in subjects with persistent inflammation. There are still many unanswered questions, the major one being what is the best treatment choice when MH is not reached?

Background: Infliximab is effective for the treatment of refractory inflammatory bowel disease (IBD). Nevertheless, up to 40% of patients lose response to infliximab over time. The aim was to assess the clinical value of measuring infliximab trough levels and antibodies to infliximab (ATI) concentrations in IBD patients who lost response to infliximab therapy., Methods: We retrospectively studied records of IBD patients who lost response to infliximab therapy. We first assessed clinical responses of different therapeutic strategies that were applied when patients lost response to infliximab and then we looked at the correlation between clinical response and infliximab trough levels and ATI concentrations., Results: Seventy-six IBD patients were included. 31/76 patients (41%) continued infliximab therapy without any modification, 39 patients (51%) had an intensification of infliximab therapy, five patients (7%) had switched to adalimumab therapy, and one patient (1%) underwent surgery. Clinical response was observed in 27 patients (69%) with an intensification of infliximab therapy. There was no significant difference in mean infliximab trough level at inclusion in patients who responded to intensification of infliximab therapy (3.3 ± 4.1 μg/mL) as compared with patients who did not respond (2.3 ± 2.2 μg/mL, P = 0.85). In all, 16/76 patients (22.4%) presented detectable ATI in the serum. Ten ATI-positive patients had an intensification of infliximab therapy and six (60%) demonstrated a clinical response. After intensification of infliximab therapy the ATI concentration decreased in five patients., Conclusions: In patients with IBD who lose response to infliximab, clinical improvement may occur upon intensification of infliximab therapy, irrespective of infliximab serum concentration or presence of ATI., (Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.)

Over the past years, mucosal healing has emerged as a major therapeutic goal in clinical trials in inflammatory bowel diseases. Accumulating evidence indicates that mucosal healing may change the natural course of the disease by decreasing the need for surgery and reducing hospitalization rates in both ulcerative colitis and Crohn's disease. Mucosal healing may also prevent the development of long-term disease complications, such as bowel damage in Crohn's disease and colorectal cancer in ulcerative colitis. Histologic healing may be the ultimate therapeutic goal in ulcerative colitis, whereas its impact on the course of Crohn's disease is unknown. Complete mucosal healing may be required before considering drug withdrawal. Targeting early Crohn's disease is more effective than approaches aimed at healing mucosa in longstanding disease. Several questions remain to be answered: should mucosal healing be systematically used in clinical practice? Should we optimize therapies to achieve mucosal healing? What is the degree of intestinal healing that is required to change the disease course? Large prospective studies addressing these issues are needed., (Copyright © 2011 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Background & Aims: Psoriasiform and eczematiform lesions are associated with anti-tumor necrosis factor (TNF)-α therapies. We assessed clinical characteristics, risk factors, and outcomes of skin disease in patients with inflammatory bowel diseases that presented with psoriasiform and eczematiform lesions induced by anti-TNF-α agents., Methods: We studied 85 patients (69 with Crohn's disease, 15 with ulcerative colitis, and 1 with indeterminate colitis; 62 women) with inflammatory skin lesions (62 psoriasiform and 23 eczematiform lesions)., Results: Twenty-four patients had a history of inflammatory skin lesions and 15 had a familial history of inflammatory skin disease. Locations of eczematiform lesions varied whereas scalp and flexural varieties were mostly psoriasiform. Skin lesions emerged but inflammatory bowel disease was quiescent in 69 patients following treatment with any type of anti-TNF-α agent (60 with infliximab, 20 with adalimumab, and 5 with certolizumab). Topical therapy resulted in partial or total remission in 41 patients. Patients with psoriasiform lesions that were resistant to topical therapy and that changed anti-TNF-α therapies once or twice developed recurring lesions. Overall, uncontrolled skin lesions caused 29 patients to stop taking TNF-α inhibitors., Conclusions: Inflammatory skin lesions following therapy with TNF-α inhibitors occurred most frequently among women and patients with a personal or familial history of inflammatory skin disease; lesions did not correlate with intestinal disease activity. Recurring and intense skin lesions caused 34% of patients in this study to discontinue use of anti-TNF-α agents., (Copyright © 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.)

The first ECCO pathogenesis workshop focused on anti-TNF therapy failures in inflammatory bowel diseases (IBDs). The overall objective was to better understand and explore primary non response and loss of response to anti-TNF agents in IBD. The outcome of this workshop is presented into two parts. This first section addresses definitions, frequency and pharmacological aspects of anti-TNF therapy failure, including pharmacokinetics of anti-TNF monoclonal antibodies and immune and non-immune mediated clearance of anti-TNF mAbs. The second section concerns the biological roles of TNF and TNF antagonists, including mechanisms of action of anti-TNF agents, and discuss hypothesis regarding their failures and phenomenon of paradoxical inflammation, including the potential role of TNF independent inflammatory pathways., (Copyright © 2010 European Crohn's and Colitis Organisation. All rights reserved.)

This second section of the first ECCO pathogenesis workshop on anti-TNF therapy failures in inflammatory bowel diseases addresses the biological roles of TNFα and the effects and mechanisms of action of TNFα antagonists. Mechanisms underlying their failure, including induction of TNF-independent inflammatory pathways and phenomena of paradoxical inflammation are discussed., (Copyright © 2010 European Crohn's and Colitis Organisation. All rights reserved.)

Endoscopy provides a direct evaluation of mucosal lesions in inflammatory bowel disease (IBD), permitting the description of elementary lesions, their surface extent and severity. The severity of mucosal lesions directly reflects disease activity and may help to identify an aggressive behavior of the disease. Several studies have recently pointed out the potential role of endoscopy in the prediction of IBD outcome. Indeed, severe endoscopic lesions in Crohn's disease (CD) patients, defined by deep and extensive ulcerations on at least one part of the colon, are associated with an increased risk of penetrating complication and surgery. Severe endoscopic lesions during severe attacks of ulcerative colitis (UC) are associated with an increased risk of colectomy in the short and long term. Severity of postoperative recurrence in CD may help to predict the risk of clinical relapse and need for further surgery. Achievement of mucosal healing, which can be obtained by administration of several types of drugs, is associated with a better outcome, less surgery and hospitalization. This review focuses on the assessment of endoscopic severity in CD and UC and on the impact of endoscopic severity on disease outcome. More specifically, we discuss how endoscopy can be used at different stages of IBD to predict the disease course and/or to adapt treatment strategies.

Background and Aim: Limited data suggests that pseudomembranes are uncommon in patients with inflammatory bowel disease (IBD) and C. difficile associated disease (CDAD), but the reason for this is unknown. We aimed to evaluate the rate of pseudomembranes in this population, identify predictive factors for pseudomembranes' presence and assess its clinical impact., Methods: This was a sub-study of a retrospective European Crohn's & Colitis Organization (ECCO) multi-center study on the outcome of hospitalized IBD patients with C. difficile. The present study included only patients who underwent lower endoscopy during hospitalization, and compared demographic and clinical parameters in the group of patients with discernable pseudomembranes versus those without., Results: Out of 155 patients in the original cohort, 93 patients underwent lower endoscopy and constituted the study population. Endoscopic pseudomembranes were found in 12 (13%) of these patients. Patients with pseudomembranes presented more commonly with fever (p=0.02) compared to patients without pseudomembranes. No difference between the two groups was found with respect to the use of immunosuppressant drugs, background demographics or disease characteristics. Neither was there a difference between the group with or without pseudomembranes in the frequency of severe adverse clinical outcome or in the duration of hospitalization. On multi-variate analysis the presence of fever remained independently associated with the finding of pseudomembranes (OR 6, 95% CI 1.2-32, p=0.03)., Conclusions: This study documents that hospitalized IBD patients with CDAD have low rate of endoscopic pseudomembranes, which is not accounted for by the use of immunosuppressant drugs. IBD patients with CDAD and discernable pseudomembranes more commonly present with fever, but their clinical outcome is similar to patients without pseudomembranes., (Copyright © 2009 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Background: Anti TNF-alpha agents are used successfully for several autoimmune diseases, including IBD and psoriasis. An emerging challenge is the increasing incidence of anti TNF-alpha induced psoriasis. A total of 120 cases have been currently reported, of whom 18 patients were treated with biological agents for IBD., Objectives: To analyse all cases of anti TNF-alpha induced psoriasis in patients with IBD in the literature and to investigate potential mechanisms of action., Methods: A literature review was performed in the PubMed, Medline, Cochrane and EMBASE databases, with simple analysis of demographic data, drug administration and psoriasis onset. Risk and incidence patient/year/duration (pyd) was calculated., Results: A total of 18 patients with IBD treated by anti TNF-alpha agents developed drug-induced psoriasis of which, 17 patients developed with infliximab, one with adalimumab. The most frequent time of onset is between 3rd and 4th infusion of infliximab. Withdrawal of infliximab led to regression of lesions in 16 patients. In six patients, infliximab was reintroduced with no further recurrence of psoriasis., Conclusions: Although anti TNF-alpha induced psoriasis is extremely rare, understanding the mechanism will be a key step towards better realizing the role played by TNF-alpha and its pharmacological inhibitors in immune-mediated diseases.