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Background and Aims: The accumulation of multiple randomized controlled trials in the field of inflammatory bowel diseases provides an opportunity to compare treatment effects between phase 2 and 3 trials. We aimed to determine whether treatment effects observed in phase 3 investigating biologics and small molecule drugs differed from those in their preceding phase 2 trial., Methods: We first performed a review of phase 2 and phase 3 trials enrolling ulcerative colitis (UC) or Crohn's disease (CD) patients. We compared the percent overall success for key endpoints between phases (several phase 3 could be matched to a single phase 2 trial). Then, we compared the percent overall success in the matched phase 2 and 3 trials (ratio 1:1), and performed sensitivity analysis., Results: We identified 14 phase 2 (8 CD; 6 UC) and 24 phase 3 (13 CD; 11 UC) trials. In CD, the different analyses suggest that the percentage of overall success of clinical remission and clinical response was significantly higher in phase 2 than in phase 3 trials. In UC, the analyses suggest collectively that the percent of treatment effect seemed similar for clinical remission, clinical response and histologic outcomes between phases but with a lower percentage of overall success in phase 2 than in phase 3 trials for endoscopic endpoints., Conclusions: In UC, we observed a similar percentage of treatment effect for clinical and histologic outcomes between phase 2 and 3 trials but not for endoscopic outcomes. Whereas in CD, we showed a failure to reproduce similar results between phases. These results may help sponsors in the design of future drug development programs., (© 2023 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Background and Aims: There is a need to evaluate the benefit-risk ratio of current therapies in inflammatory bowel disease (IBD) patients to provide the best quality of care. The primary objective of I-CARE (IBD Cancer and serious infections in Europe) was to assess prospectively safety concerns in IBD, with specific focus on the risk of cancer/lymphoma and serious infections in patients treated with anti-tumor necrosis factor and other biologic monotherapy as well as in combination with immunomodulators., Methods: I-CARE was designed as a European prospective longitudinal observational multicenter cohort study to include patients with a diagnosis of Crohn's disease, ulcerative colitis, or IBD unclassified established at least 3 months prior to enrollment., Results: A total of 10,206 patients were enrolled between March 2016 and April 2019, including 6169 (60.4%) patients with Crohn's disease, 3853 (37.8%) with ulcerative colitis, and 184 (1.8%) with a diagnosis of IBD unclassified. Thirty-two percent of patients were receiving azathioprine/thiopurines, 4.6% 6-mercaptopurine, and 3.2% methotrexate at study entry. At inclusion, 47.3% of patients were treated with an anti-tumor necrosis factor agent, 8.8% with vedolizumab, and 3.4% with ustekinumab. Roughly one-quarter of patients (26.8%) underwent prior IBD-related surgery. Sixty-six percent of patients had been previously treated with systemic steroids. Three percent of patients had a medical history of cancer prior to inclusion and 1.1% had a history of colonic, esophageal, or uterine cervix high-grade dysplasia., Conclusions: I-CARE is an ongoing investigator-initiated observational European prospective cohort study that will provide unique information on the long-term benefits and risks of biological therapies in IBD patients. (EudraCT, Number: 2014-004728-23; ClinicalTrials.gov, Number: NCT02377258)., (Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Faecal incontinence (FI) is a disabling condition in patients with inflammatory bowel disease (IBD). The diagnosis of FI is not easy as patients are reluctant to report this embarrassing symptom. The objectives of this study were to characterize the prevalence of FI in IBD patients using available scoring systems, and to identify associated risk factors., Methods: A FI clinic was implemented in routine practice between January 2020 and April 2021. FI was defined as a Wexner score ≥5. Factors associated with FI were analyzed., Results: A total of 319 consecutive patients with IBD were included. The prevalence of FI was 16.4% (53/319). Age >45 years at inclusion (Odd ratio (OR)=3.33, Confidence interval (CI) 95% 1.40-7.94), diarrhea (three stools at least per day) (OR=2.94, CI 95% 1.16-7.45), stool consistency according to the Bristol stool chart (OR=2.23, CI 95% 1.00-4.99), and abdominal pain (OR=2.24, CI 95% 1.10-4.53) were independently associated with FI in a multivariate model analysis., Conclusions: Approximately one fifth of IBD patients reported FI in this real-world cohort, using an available scoring system. Increased age, diarrhea, stool consistency according to the Bristol stool chart, and abdominal pain were associated with FI. A systematic screening of FI would allow a better management of this disabling condition., Competing Interests: Declaration of Competing Interest S Kurt declares no conflict of interest. B Caron has received lecture and/or consulting fees from Abbvie, Amgen, Celltrion, Janssen, Takeda. C Gouynou has received lecture fees from Janssen and Takeda. P Netter declares no conflict of interest. S Danese has served as a speaker, consultant, and advisory board member for Schering-Plough, AbbVie, Actelion, Alphawasserman, AstraZeneca, Cellerix, Cosmo Pharmaceuticals, Ferring, Genentech, Grunenthal, Johnson and Johnson, Millenium Takeda, MSD, NikkisoEurope GmbH, Novo Nordisk, Nycomed, Pfizer, Pharmacosmos, UCB Pharma and Vifor. CJ Vaizey has served as a speaker and consultant for Medtronic, advisory board member and speaker for Acelity, consultant for Renew Medical. SD Wexner has received royalties for intellectual property license from Intuitive, Karl Storz, and Medtronic and Consulting fees for consulting by Medtronic, Stryker, Intuitive, Astellas, Olympus, ARC Medical Devices, and Takeda. C Baumann declares no conflict of interest. L Peyrin-Biroulet has served as a speaker, consultant and advisory board member for Merck, Abbvie, Janssen, Genentech, Mitsubishi, Ferring, Norgine, Tillots, Vifor, Hospira/Pfizer, Celltrion, Takeda, Biogaran, Boerhinger-Ingelheim, Lilly, HAC- Pharma, Index Pharmaceuticals, Amgen, Sandoz, For- ward Pharma GmbH, Celgene, Biogen, Lycera, Samsung Bioepis, Theravance., (Copyright © 2022. Published by Elsevier Ltd.)

Background and Aims: Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), and human immunodeficiency virus (HIV) both impact innate and adaptive immunity in the intestinal mucosa. As it is a rare situation, the intersection between HIV and IBD remains unclear, especially the impact of HIV infection on the course of IBD, and the drug safety profile is unknown., Methods: We conducted a multicenter retrospective cohort study between January 2019 and August 2020. All adult patients with IBD and concomitant HIV infection were included. Each IBD patient with HIV was matched to two HIV-uninfected IBD patients., Results: Overall, 195 patients with IBD were included, including 65 HIV-infected patients and 130 without HIV infection. Of the 65 infected patients, 22 (33.8%) required immunosuppressants and 31 (47.7%) biologics. In the HIV-infected group, the need for immunosuppressants (p = 0.034 for CD and p = 0.012 for UC) and biologics (p = 0.004 for CD and p = 0.008 for UC) was significantly lower. The disease course, using a severity composite criterion, was not significantly different between the two groups for CD (hazard ration (HR) = 1.3 [0.7; 2.4], p = 0.45) and UC (HR, 1.1 [0.5; 2.7], p = 0.767). The overall drug safety profile was statistically similar between the two groups., Conclusion: Although HIV-infected patients receive less treatments, the course of their IBD did not differ than uninfected, suggesting that HIV infection might attenuate IBD. The drug safety profile is reassuring, allowing physician to treat these patients according to current recommendations., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: The diagnosis of iron deficiency is based on ferritin and transferrin saturation (TfS) in inflammatory bowel disease (IBD) patients, yet guideline thresholds are not evidence-based. Soluble transferrin receptor (sTfR) is one of the best noninvasive tests in patients with inflammation., Aims: To evaluate the accuracy of ferritin and/or TfS for diagnosing iron deficiency in IBD and identify the optimal thresholds of these parameters using sTfR as reference., Methods: Two hundred and two patients (2072 samples) receiving at least one infusion of biologic (vedolizumab or infliximab) were included., Results: In ulcerative colitis patients with C-reactive protein (CRP) <10 mg/L, optimal iron deficiency diagnostic performances were observed with ferritin and TfS thresholds of 65 µg/L (sensitivity of 0.78 and specificity of 0.76) and 16% (sensitivity of 0.79 and specificity of 0.90), respectively. For ulcerative colitis patients with CRP > 10 mg/L, the thresholds with the best diagnostic performance were 80 µg/L (sensitivity of 0.75 and a specificity of 0.82) for ferritin and 11% for TfS (sensitivity of 0.75 and a specificity of 0.82). There was no added value for combined ferritin and TfS. No ferritin or TfS threshold had good diagnostic performance in Crohn's disease patients (AUC for ferritin was 0.65 (95% CI 0.55-0.75) and the AUC for TfS was 0.70 (95% CI 0.61-0.78)., Conclusion: Ferritin and TfS are reliable parameters for iron deficiency diagnosis only in ulcerative colitis patients, at thresholds different from current guidelines. In Crohn's disease patients, sTfR should be used given the poor diagnostic performance of ferritin and TfS., (© 2020 John Wiley & Sons Ltd.)

Background: Primary sclerosing cholangitis (PSC) is a major concern in inflammatory bowel disease (IBD)., Aims: Evaluating the use of magnetic resonance cholangiography (MRC) as a screening tool for PSC in IBD patients., Methods: A single-center cohort study investigating systematic MRC to assess PSC in IBD patients with (cohort 1) and without (cohort 2) liver function tests (LFTs) abnormality, combined with a retrospective analysis of MRCs in a control group of non-IBD patients with abnormal LFTs (cohort 3)., Results: In total, 420 patients (cohort 1: n = 203, cohort 2: n = 30, cohort 3: n = 187) underwent imaging. MRC was classified 'abnormal' in 49/203 (24.1%) patients in cohort 1, in 1/30 (3.3%) patients in cohort 2, and in 66/187 (35.3%) patients in cohort 3 (p < 0.004 for all comparisons). PSC was diagnosed in 20/203 (9.9%) patients in cohort 1, in 1/30 (3.3%) patients in cohort 2, and in 13/187 (7.0%) patients in cohort 3 (p = 0.44). Gamma-glutamyl transpeptidase was the only independent factor predicting the diagnosis of PSC in IBD (OR 1.8, 95% CI 1.3-2.5, p = 0.001)., Conclusions: MRC revealed PSC in one tenth of IBD patients with abnormal LFTs and should be systematically performed in IBD patients with abnormal LFTs, especially if gamma-glutamyl transpeptidase level is elevated., (Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background and Aims: The vaccination rate against hepatitis B virus (HBV) is low in inflammatory bowel disease (IBD) patients. The Consensus from the European Crohn's and Colitis Organisation on opportunistic infections recommends testing all IBD patients for HBV at diagnosis and vaccinating all HBV-negative patients. We compared the efficacy of HBV vaccine between IBD patients and healthy controls and investigated the impact of immunosuppressive therapy on vaccine response in IBD patients., Materials and Methods: IBD patients and healthy adult workers were vaccinated against HBV following a standard protocol (at 0, 1, and 6 months; Engerix B). The efficacy of vaccination was evaluated at 8 months by a titer of antibodies against hepatitis B surface antigen (anti-HBs)., Results: Among 164 participants (96 with IBD and 68 healthy workers), the level of anti-HBs was greater than 10 IU/l in 80.2 and 94.1% (P=0.0115) of IBD patients and healthy controls, respectively, and anti-HBs levels greater than 100 IU/l were seen in 45.8 versus 77.9% (P<0.0001) of IBD patients and healthy controls, respectively. The median level of anti-HBs was significantly higher in healthy controls (497.0±386.2) than in IBD patients (253.9±34.5) (P<0.0001). None of the baseline characteristics of IBD patients, including immunomodulators and antitumor necrosis factor therapy, influenced the vaccine response. In the multivariate analysis, ileal disease was the only factor associated with a lower response to the vaccine (odds ratio=3.2; 95% confidence interval=1.0-9.7; P=0.049)., Conclusion: The response rate to HBV vaccination is significantly lower in IBD patients than in the general population. Immunosuppressive therapy for IBD did not influence the vaccine response.

Background and Aims: We investigated the beliefs and behaviours about tobacco among inflammatory bowel disease (IBD) patients., Materials and Methods: A questionnaire of 18 items was developed and administered to all consecutive patients followed for IBD at Nancy University Hospital from October 2012 to March 2013., Results: Two hundred and thirty-one patients participated in the survey [Crohn's disease (CD)=171, ulcerative colitis (UC)=60]. Among IBD patients who were smokers at diagnosis, 10.5% of CD patients versus 14.3% of UC patients believed that tobacco could have triggered their IBD; about half the CD smokers at diagnosis were not aware that smoking might promote their disease. Three quarters of smokers after diagnosis knew that tobacco was not beneficial for their CD, whereas all UC were aware that smoking had a beneficial effect on their disease course. About half of the CD patients had stopped smoking during a flare-up. Four former smokers with UC (21.1%) resumed smoking during a relapse. Nearly 90% of IBD current smokers wished to quit smoking. About half the IBD patients were aware of the relation between smoking and IBD, and the Internet was a source for 24.3% of these patients., Conclusion: The majority of IBD patients are unaware of the effects of tobacco on their disease. Better information through a therapeutic education programme should be systematically recommended in IBD.

Introduction: Data about the safety of vedolizumab and ustekinumab are lacking in older patients with inflammatory bowel disease. The objective was to compare the safety of vedolizumab and ustekinumab therapies in older patients (>60 years) with inflammatory bowel disease. Methods: This retrospective study included patients with Crohn's disease or ulcerative colitis initiating vedolizumab, ustekinumab or anti-TNF therapy at >60 years of age. We examined the occurrence of adverse events within one year after therapy. Results: This study included 182 patients: 53 were treated with vedolizumab (22 patients with Crohn's disease and 31 with ulcerative colitis), 31 with ustekinumab (30 Crohn's disease and one ulcerative colitis) and 98 with anti-TNF (63 Crohn's disease and 35 ulcerative colitis). At one year, there was no difference in terms of safety in patients with Crohn's disease between vedolizumab and ustekinumab considering the number of adverse events per year of follow-up (p = 0.258). For ulcerative colitis and Crohn's disease, the occurrence of adverse events per year of follow-up was similar between vedolizumab and anti-TNF (p = 0.274 and p = 0.876, respectively). Conclusions: Safety was similar between vedolizumab and ustekinumab in older patients with inflammatory bowel disease. [ABSTRACT FROM AUTHOR]

Background: Extra-intestinal manifestations are frequent in inflammatory bowel disease (IBD). Ocular disorders are generally under diagnosed as they are challenging diagnosis. Aims: We assessed the prevalence of ophthalmological manifestations in patients with IBD, and investigated characteristics associated with ocular manifestations. Methods: We performed a retrospective study including patients followed for IBD and had an ophthalmologic visit from January 2013 to July 2020, among 1432 patients followed during this period. Two groups were considered: the first group included patients whose an ocular diagnosis was considered as "related to IBD", and the second group including patients whose an ocular diagnosis was considered "not related to IBD". Results: Among 1432 patients with IBD, eighty-seven (6.1%) patients had an ophthalmologic visit. Fifty-three patients (3.7%) were considered to have an ocular extra-intestinal manifestation or an iatrogenic effect of IBD treatment, and 34 diagnoses (2.4%) were considered not related to IBD. Inflammatory surface pathologies were the most frequent (33.2%), including 15 patients with dry eye (17.2%), 9 with blepharitis (10.3%), and 5 with chalazions (meibomian cyst) (5.7%). Uveitis was diagnosed in 13 patients (14.9%), episcleritis in 5 patients (5.7%), and scleritis in 2 patients (2.3%). Characteristics of patients with an ophthalmological diagnosis "related to IBD" versus "not related to IBD" were not statistically different. Conclusion: In our cohort, less than 5% of patients had ophthalmological extra-intestinal manifestation. The most frequent ocular diagnosis were dry eye and uveitis. No disease characteristics of IBD were found to be associated with ocular manifestations. [ABSTRACT FROM AUTHOR]

Patients with Crohn's disease (CD) are at risk for short bowel syndrome (SBS). We investigated independent predictors for SBS in these patients to allow the development of preventive strategies. All adult patients seen at the Nancy University hospital for CD or SBS between 2012 and 2019 were eligible for inclusion in this case-control study. Each CD patient with SBS was matched to 9 controls. 410 CD patients were included (369 without SBS and 41 with SBS). Subjects with SBS underwent significantly more bowel resections (median value of 3 vs 1, p<0.0001) and median time before the first surgery was not different than controls (6 vs 4 years, p=0.59). A higher need for parenteral support was found in end-jejunostomy SBS than in jejunocolic and jejunoileal SBS (70.6% vs 25% and 0%, p=0.0031). Montreal B1 behavior (OR 0.02, CI 95% 0-0.08) and budesonide treated-patients (OR=0.03, CI 95% 0.003-0.2) were at lower risk of SBS, while IV steroid treated-patients were at higher risk (OR=8.5, CI 95% 3.0-24.9). Montreal B1 behavior, IV steroids and budesonide use are influencing predictors for this complication. These predictors should be assessed in daily clinical practice to prevent SBS occurrence. [ABSTRACT FROM AUTHOR]

Summary: Background: Although influenza and pneumococcal vaccinations for high‐risk populations are recommended by current guidelines, vaccination coverage is low in patients with gastrointestinal cancer (GC) or inflammatory bowel disease (IBD). Aim: To evaluate the impact of a specialised infectious disease consultation on vaccination coverage rates in these patients. Methods: Between December 2016 and April 2017, all patients with GC or IBD followed in the outpatient clinic of the Gastroenterology department at the Nancy University Hospital enrolled in a 3‐phase vaccination programme. Phase 1: Initial questionnaire (vaccination status, knowledge about vaccines and possible barriers to vaccination); Phase 2: Infectious disease consultation; Phase 3: Subsequent questionnaire (evolution of patients' knowledge about vaccination). Results: A total of 366 patients were included (GC = 99, IBD = 267). Vaccination rate was 34.7% for influenza and 14.5% for pneumococcus. About 43% of the patients feared side effects of vaccines. After the initial questionnaire, 49.3% of the interested patients participated in a specialised vaccination consultation (n = 102). 87.3% (n = 89) received new vaccination, 41.2% changed their mind about vaccination, and 92.2% would recommend this programme to other patients. Among vaccinated patients, 97.8% (n = 87) received pneumococcal vaccine, 40.4% received tetanus‐diphtheria‐polio vaccine, and 7.9% received influenza vaccine. In GC patients, anti‐pneumococcal vaccination rate was 87.5% after the specialised consultation compared with 10.1% before. In IBD patients, corresponding rates were 85.7% and 16.1%. Conclusions: A specialised infectious disease consultation can improve GC and IBD patients' knowledge about vaccination and vaccination coverage. This approach could be applied to all high‐risk populations. [ABSTRACT FROM AUTHOR]

Objectives:The broader and prolonged use of anti-tumor necrosis factor (TNF) agents in inflammatory bowel disease (IBD) could expose patients to an increased risk of adverse reactions, including dermatological complications. We assessed the cumulative incidence of anti-TNF-induced cutaneous adverse reactions in IBD patients, their risk factors, their dermatological management, and their outcome in a large cohort of IBD patients.Methods:In a single-center observational retrospective study, including all consecutive adult IBD patients treated with an anti-TNF agent between 2001 and 2014, all patients with dermatological complications under anti-TNF therapy were identified in a well-defined cohort of IBD patients. We conducted a survival analysis to determine the cumulative incidence of dermatological complications and risk factors for developing any dermatological complications, cutaneous infections, and psoriasiform lesions. Survival curves were estimated by the Kaplan-Meier method, and we used a Cox proportional hazards model to test the association between parameters and time to each event: any dermatological complication, cutaneous infections, and psoriasis lesions.Results:Among 583 IBD patients, 176 dermatological complications occurred, involving 20.5% of patients. Median duration of follow-up was 38.2 months (range: 1-179). Psoriasiform lesions (10.1%; 59/583) and cutaneous infections (11.6%, 68/583) were the most frequently observed, with a cumulative incidence of, respectively, 28.9% and 17.6% at 10 years. They led to anti-TNF discontinuation, respectively, in 18.6% and 2.9% of patients. In case of switching to another anti-TNF agent for psoriasiform lesions, recurrence occurred in 57% of patients. Ulcerative colitis was associated with a lower risk of developing cutaneous infections than Crohn's disease (hazard ratio (HR)=0.25; 95% confidence interval (CI)=0.09-0.68; P=0.007). Higher dosing of anti-TNF agent was associated with a higher risk of developing cutaneous infections (HR=1.99; 95% CI=1.09-3.64; P=0.025). A younger age at time of anti-TNF initiation was associated with a higher risk of dermatological complications (HR=2.25; 95% CI=1.39-3.62; P<0.001).Conclusions:Dermatological complications involve one of five patients treated with anti-TNF therapy after a 14-year follow-up. Association of cutaneous infections with higher anti-TNF dosing suggests a dose-dependent effect. Discontinuation of anti-TNF therapy due to dermatological complications is required in one out of five patients with psoriasiform lesions, but specific dermatological treatment allows to continue anti-TNF therapy in half of them. [ABSTRACT FROM AUTHOR]