Search

Background: Specific studies on the impact of ulcerative colitis (UC) and bowel urgency (BU) on disability and quality of life (QoL) of patients on advanced therapies are missing., Methods: Clinical and therapeutic management data were collected by Gastroenterologists from adult patients with UC treated with advanced therapies. Patients reported outcomes on QoL were collected using patient-reported questionnaires., Results: Forty-one sites enrolled 293 patients. Median age was 42.0 years, median disease duration was 6.0 years. 38.9 % had active disease (partial Mayo score>1). Median treatment duration was 16.9 months. 166 (57.0 %) patients had BU [median UNRS=2] and 78.3 % had fecal incontinence [median Wexner score=8.0]. Moderate to severe disability (IBD-Disk score≥40) was reported in 37.8 % patients. BU patients had a higher Wexner score [10.0 vs 5.2, p < 0.0001] and moderate to severe disability rate (53.7% vs 16.9 %, p < 0.0001), lower QoL and work productivity than those in BU remission: mean EQ-5D-5 L utility [0.846 vs 0.943, p < 0.0001], VAS for self-rated health [66.2 vs 82.1, p < 0.0001], and overall work impairment [35.7% vs 11.3 %, p < 0.0001]., Conclusion: The burden of moderate to severe UC, especially in patients with BU, is high. These findings highlight that BU control remains an unmet medical need in UC patients and underscore the need for new innovative treatments., Competing Interests: Conflicts of interest Justin Kirion and Stéphane Bouée are employed by CEMKA who received an unrestricted grant to perform the study. Camille Robert, Vincent Ghestem and Isabelle Jamonneau are employed by the company Lilly. Mathurin Fumery Consultant for Abbvie, Sandoz, Celltrion, Arena, MSD, Lilly, Pfizer, Ferring, Tillots, Takeda, Amgen, Biogen, Fresenius, and Nordic Pharma. Romain Altwegg: Advisory boards for Abbvie, Takeda, Galapagos, Amgen, Sandoz, Lilly, Pfizer, and Janssen. Jérome Filippi: Abbvie, Amgen Biogen, Celltrion, Galapagos, Janssen, MSD, Pfizer, Sandoz, and Takeda. Philippe Aygalenq: Philippe Aygalenq: Consultant for Janssen Cilag, Pfizer, MSD, Abbvie, and Takeda., (Copyright © 2024 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: There is a need for published data on real-world use of SB5, an adalimumab (ADL) biosimilar approved in Europe in 2017, on the basis of evidence from pre-clinical and analytic data as well as phase I and III clinical studies demonstrating equivalent efficacy and comparable pharmacokinetics, safety and immunogenicity profiles as the reference ADL., Objectives: The purpose of this study was to estimate patient persistence on SB5 at 12 months post-initiation using clinical and healthcare claims data from the French Système National des Données de Santé (national healthcare claims database, SNDS) in addressing data gaps., Methods: PERFUSE is a 12-month, observational, multi-centre cohort study of patients with rheumatic or gastrointestinal immune-mediated inflammatory diseases (IMIDs) who initiated routine SB5 treatment between October 2018 and October 2020, either as their first ADL (naïve) or transitioning from another ADL (switched). Clinical data, including disease activity scores, C-reactive protein levels, and dosing information, were collected as available from patient records captured during routine visits to specialist physicians. Persistence data were supplemented with data from the French national healthcare claims database (SNDS). Analyses of clinical data were descriptive, while persistence was assessed using a Kaplan-Meier survival analysis., Results: Overall, 911 patients were included: 507 from rheumatology centres [116 with rheumatoid arthritis (RA), 78 psoriatic arthritis (PsA), and 313 ankylosing spondylitis (AS)] and 404 from gastroenterology centres [316 with Crohn's disease (CD) and 88 ulcerative colitis (UC)]. Among naïve patients, 12-month remission/low activity rates were 58% for RA, 66% for PsA, 59% for AS, 94% for CD, and 85% for UC, increasing significantly from baseline for all indications (p < 0.05). Switched patients' remission rates remained stable between baseline and month 12 (M12) for all indications (p > 0.05). Persistence (95% CI) at M12 among naïve patients was 59% (46.5, 68.8) for RA, 65% (49.7, 77.1) for PsA, 56% (48.3, 62.6) for AS, 70% (63.0, 75.7) for CD, and 42% (30.7, 53.1) for UC, compared to 60% (42.7, 73.7) for RA, 57% (37.3, 72.1) for PsA, 55% (45.8, 64.0) for AS, 63% (53.4, 71.7) for CD, and 56% (27.2, 77.6) for UC among switched patients. No significant differences were observed between naïve and switched patients (p > 0.05). SNDS pairing provided information on 68 of the 132 patients (52%) who were lost to follow-up in the clinical database, of whom 57 (84%) were confirmed persistent at M12 and 11 (16%) non-persistent. Primary treatment failure (naïve patients) and patient decision (switched patients) were the most common reasons stated for treatment discontinuation., Conclusions: SB5 provides clinically effective treatment of both gastrointestinal and rheumatic IMIDs for naïve and switched patients, with no loss of control observed when switching. Persistence was comparable between naïve and switched populations, though the reasons for non-persistence differed., Trial Registry: Trial registration number: Clinical Trials identifier NCT03662919. Trial registration date: 10 September 2018., Competing Interests: Declarations. Funding: This study was sponsored by Biogen Int GmbH (Baar, Switzerland). Funding was provided by Biogen. Open access fees were sponsored by Biogen Int GmbH (Baar, Switzerland). Conflict of interest: Bruno Fautrel: received speaker/consulting fees from AbbVie, Biogen, Boehringer Ingelheim, BMS, Celgene, Janssen, Lilly, Medac, MSD, NORDIC Pharma, Novartis, Pfizer, Roche, Sobi and UCB, and grant/research support from AbbVie, MSD and Pfizer. Yoram Bouhnik: received consultancy and/or speaker fees from AbbVie, Biogaran, Biogen, Boehringer Ingelheim, CTMA, Ferring, Gilead, Hospira, ICON, Inception IBD, Janssen, Lilly, Mayoly Spindler, Merck, Merck Sharp & Dohme, Norgine, Pfizer, Robarts Clinical Trials, Roche, Sanofi, Shire, Takeda, UCB and Vifor Pharma. Carine Salliot: received consultancy and/or speaker fees from Novartis, Roche-Chugai, Pfizer and Galapagos, and grant/research support from Roche-Chugai and Novartis. Frank Carbonnel: received speaker fees from Abbvie, Astra, Biocodex, Biogen, Ferring, Janssen, MSD, Pfizer, Pileje, Takeda, Tillotts; and is a member of advisory boards for Amgen, Arena, BMS, Celltrion, Enterome, Ferring, Janssen, Medtronic, Pfizer, Pharmacosmos, Roche and Tillotts. Mathurin Fumery: received consultancy and/or speaker fees from AbbVie, Biogen, Boehringer Ingelheim, CTMA, Ferring, Gilead, Hospira, Janssen, Lilly, Merck Sharp & Dohme, Pfizer, Takeda, Tillots and Celgene. Chirstophe Bernardeau: nothing to disclose with respect to their contributions to this work. Yves Maugars: nothing to disclose with respect to their contributions to this work. Mathurin Flamant: received consultancy and/or speaker fees from AbbVie, Amgen, Biogen, Ferring, Janssen, Mayoly Spindler, Merck Sharp & Dohme, Pfizer, Takeda, Tillots and Pharma. Fabienne Coury: received speaker/consulting fees from Abbvie, Amgen, BMS, Janssen, Lilly, MSD, Novartis, Pfizer, Roche-Chugai, Sanofi and UCB, and grant/research support from Abbvie, Biogen, Celgene, Chugai, Novartis, Pfizer and UCB. Ben Braithwaite: no conflicts of interest to disclose. Salima Hateb: is an employee of and may hold stock in Biogen. Janet Addison: is an employee of and may hold stock in Biogen. Availability of data and material: The datasets generated and analysed during the current study are not publicly available as data for this study contain potentially identifying information. Ethics approval: All necessary ethical considerations and measures were taken to ensure the protection of all participants: patients were eligible for the study only if they were able to understand and sign a consent form. This study is listed on clinicaltrials.gov under the identifier NCT03662919 and was approved by the appropriate bodies in terms of quality of methodology, data security and scientific merit. The final amendment to the protocol for this study was approved by an independent ethics committee (Comité de Protection des Personnes, CPP) in France on 25 April 2019, in accordance with French regulations (CPP SUD-EST II; study ref. 2018-06; internal ref. 19.03.29.73319). Furthermore, this study conformed to all regulations concerning the use of personal data. All procedures were carried out in accordance with the ethical rules and the principles of the Declaration of Helsinki and its later amendments. Consent to participate: Informed consent was obtained from all individual participants included in the study in the form of a non-opposition form signed and archived by the physician in accordance with French regulations. Code availability: The code used to perform data management and run the analyses uses proprietary modules owned by eXYSTAT. Thus, the code cannot be made publicly available. Author contributions: Bruno Fautrel: as the coordinating investigator for rheumatology, made substantial contributions to the conception and design of the work, the acquisition and interpretation of data for the work and reviewed all draft versions of the manuscript for important intellectual content. Yoram Bouhnik: as the coordinating investigator for gastroenterology, made substantial contributions to the conception and design of the work, the acquisition and interpretation of data for the work and reviewed all draft versions of the manuscript for important intellectual content. Carine Salliot: as an investigator, made substantial contributions to the acquisition and interpretation of data for the work and reviewed all draft versions of the manuscript for important intellectual content. Mathurin Fumery: as an investigator, made substantial contributions to the acquisition and interpretation of data for the work and reviewed all draft versions of the manuscript for important intellectual content. Chirstophe Bernardeau: as an investigator, made substantial contributions to the acquisition and interpretation of data for the work and reviewed all draft versions of the manuscript for important intellectual content. Mathurin Flamant: as an investigator, made substantial contributions to the acquisition and interpretation of data for the work and reviewed all draft versions of the manuscript for important intellectual content. Fabienne Coury: as an investigator, made substantial contributions to the acquisition and interpretation of data for the work and reviewed all draft versions of the manuscript for important intellectual content. Ben Braithwaite: as the lead writer and biostatistics coordinator for this work, made substantial contributions to the design of the work, acquisition, analysis and interpretation of data for the work and produced all draft versions of the manuscript. Salima Hateb: as a study coordinator for the sponsor, made substantial contributions to the conception and design of the work, the acquisition and interpretation of data for the work and reviewed all draft versions of the manuscript for important intellectual content. Janet Addison: as the sponsor’s lead scientist for this work, made substantial contributions to the conception and design of the work, the analysis and interpretation of data for the work and critically reviewed, commented upon and edited all draft versions of the manuscript. The first draft of the manuscript was written by Ben Braithwaite and all authors commented on previous versions of the manuscript. All authors read, provided input and approved the final manuscript. All authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved., (© 2024. The Author(s).)

Competing Interests: The authors declare that they have no conflict of interest.

Background & Aims: The aim of this study was to assess the long-term effectiveness and safety of risankizumab maintenance treatment in a large real-world cohort of patients with Crohn's Disease (CD)., Methods: From May 2021 to August 2023, all consecutive patients with CD treated with risankizumab in 25 GETAID centers have been retrospectively included. The primary endpoint was steroid-free clinical remission (Harvey Bradshaw Index [HBI] <5) at 52 weeks., Results: Of the 174 patients included, 99%, 93%, and 96% had been previously exposed to anti-TNF, vedolizumab, and ustekinumab, respectively. All patients had received ≥3 biologics, and 108 (62%) had previous intestinal resection. Median follow-up was 13.7 months (interquartile range, 10.0-18.1 months). The rates of steroid-free clinical remission and clinical remission at week 26 were 47% (72/152) and 52% (79/152), and 46% (58/125), and 48% (60/125) at week 52, respectively. Risankizumab persistence rates were 94%, 89%, and 79% at weeks 12, 26, and 52, respectively. At the end of follow-up, 45 (45/174; 26%) patients had discontinued risankizumab (loss of response, 42%; primary failure, 37%; intolerance, 13%). Thirty-six patients (36/174; 20.9%) were hospitalized, and 22 (22/174; 12.6%) required intestinal resection. Fifty-one patients (29%) had an adverse event, including 26 (15%) serious adverse events (CD flare, n = 17). One death (myocardial infarction) and one cancer (papillary thyroid carcinoma) were observed., Conclusion: This is the first real-life study to report long-term outcomes in patients with refractory CD treated with risankizumab. One-half of the patients achieved steroid-free clinical remission after 1 year, and the safety profile was consistent with the literature., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Breast cancer is the most common malignancy observed in patients with inflammatory bowel diseases (IBD). The aim of our study was to evaluate incident cancer rate (recurrence or new-onset cancer) in a cohort of patients with IBD with a history of breast cancer according to the subsequent IBD treatment provided., Methods: A multicenter retrospective study included consecutive patients with IBD with prior breast cancer. The inclusion date corresponded to the diagnosis of index malignancy. Follow-up lasted from cancer diagnosis until the occurrence of incident cancer., Results: Among 207 patients included (median disease duration, 13 years [interquartile range, 6-21]), first-line treatment (median interval of 28 months [interquartile range, 7-64]) was a conventional immunosuppressant in 19.3% of patients, anti-tumor necrosis factor in 19.8%, vedolizumab in 7.2%, and ustekinumab in 1.9%. After a median follow-up of 71 months (interquartile range, 34-148), 42 (20%) incident cancers were observed (34 breast cancer recurrences). Adjusted incidence rates per 1000 person-years were 10.2 (95% confidence interval, 6.0-16.4) for the untreated arm and 28.9 (95% confidence interval, 11.6-59.6) for exposed patients (P = .0519). There was no significant difference between treated patients and control subjects regarding incident cancer-free survival rates (P = .4796). In multivariable analysis, factors associated with incident cancer were stage T4d (P = .036), triple negative tumor (P = .016), and follow-up of less than 71 months (P = .005)., Conclusions: We did not find a statistically significant increase in incident breast cancer related to IBD treatment beyond the already known poor prognostic factors of breast cancer., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background and Aims: Achieving deep remission, encompassing clinical, endoscopic, and biological remission, is the goal in managing Crohn's disease (CD). The role of histological remission remains unclear. This study aimed to examine the impact of histological inflammation on clinical relapse risk in CD and explore the relationship between histology, endoscopic scores, and biomarkers., Methods: Patients from the prospective STORI cohort underwent ileocolonoscopy with CDEIS calculation and 2 biopsies from the most inflamed or previously inflamed areas. Histological scores (Robarts, Geboes, modified Geboes, Nancy, and IBD-DCA) were determined by two independent pathologists in a central reading process. Histological remission was defined by specific score thresholds. Clinical relapse, defined by CDAI >250 or a CDAI increase of 70 points over two weeks, was monitored for at least one year., Results: Out of 115 patients included in STORI, 160 biopsies (44 ileal and 116 colonic) from 76 patients were analyzed. Histological remission rates were 46% (Nancy), 55% (Robarts), 61% (Geboes), and 41% (IBD-DCA). During follow-up, 35 patients (46%) experienced a clinical relapse: 37% with histological remission and 56% without, based on the Nancy score. Among the mucosal healing (MH) subgroup (45 patients), 34% with histological remission and 44% without relapsed (p=0.18). Histological scores did not predict clinical relapse. Only faecal calprotectin (FC) was a significant predictor in multivariate analysis (p=0.029)., Conclusion: Despite correlations with endoscopy and biomarkers, histological scores did not predict clinical relapse in CD patients in remission. Thus, these scores are not recommended for clinical practice to assess relapse risk in CD., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Mucosal healing (MH) is an established treatment goal in inflammatory bowel disease (IBD). However, various definitions of MH exist. We aimed to identify how MH is defined in randomized controlled trials (RCTs) in ulcerative colitis (UC) and Crohn's disease (CD)., Methods: We searched MEDLINE, EMBASE, and the Cochrane library from inception to December 2023 for phase 2 and 3 RCTs of advanced therapies in IBD., Results: One hundred forty-four studies were included, 72 in UC and 72 in CD, published between 1997 and 2023. In UC, 64% (46/72) RCTs reported MH as an endpoint. 12 definitions of MH were found, from endoscopic assessment alone (35/46; 76%) to the more recent combination of histology and endoscopy (10/46; 22%). 96% (44/46) of studies used the Mayo Endoscopic Subscore. In CD, reporting of MH lagged behind UC, with only 12% (9/72) of trials specifically defining MH as an endpoint, 7 as "absence of ulceration," 2 as Simplified Endoscopic Score for CD score ≤2 or 0. Histological assessment was performed in 3 RCTs of CD. Centralized reading of endoscopy was used in 48% (35/72) of RCTs of UC and 22% (16/72) of CD. Only 1 RCT included transmural healing as an endpoint., Conclusions: A standard definition of MH in IBD is lacking. Definitions have evolved particularly in UC, which now includes the addition of histological evaluation. Transmural healing holds promise as a future target in CD. We support a greater standardization of definitions as we expect endpoints to become increasingly stringent and multimodal with computers automating the assessment., (© 2024 The Author(s). United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Background: In industrialized countries, the incidence of inflammatory bowel disease (IBD) appears stabilized. This study examined the incidence and phenotype of IBD in Northern France over a 30-year period., Methods: Including all IBD patients recorded in the EPIMAD population-based registry from 1988 to 2017 in Northern France, we described the incidence and clinical presentation of IBD according to age, sex and time., Findings: A total of 22,879 incident IBD cases were documented (59% (n = 13,445) of Crohn's disease (CD), 38% (n = 8803) of ulcerative colitis (UC), 3% (n = 631) of IBD unclassified (IBDU)). Over the study period, incidence of IBD, CD and UC was 12.7, 7.2 and 5.1 per 10 5 person-years, respectively. The incidence of CD increased from 5.1/10 5 in 1988-1990 to 7.9/10 5 in 2015-2017 (annual percent change (APC): +1.9%, p < 0.0001). The incidence of UC increased from 4.5/10 5 to 6.1/10 5 (APC: +1.3%, p < 0.0001). The largest increase was observed in children (+4.3% in CD, p < 0.0001; +5.4% in UC, p < 0.0001) followed by young adults aged 17-39 years (+1.9% in CD, p < 0.0001; +1.5% in UC, p < 0.0001). The increase in UC incidence was significantly higher in women than in men (+1.9% in women, +0.8% in men; p = 0.006). We estimated that in our area, by 2030, nearly 0.6% of the population will have IBD., Interpretation: The persistent increase of IBD incidence among children and young adults but also in women with UC in Northern France, suggests the persistence of substantial predisposing environmental factors., Funding: Santé Publique France; INSERM; Amiens, Lille and Rouen University Hospitals., Competing Interests: Guillaume Savoye has served as speaker for MSD France, Ferring France, Abbvie France, and Vifor France. Mathurin Fumery has received lecture/consultant fees from Abbvie, Ferring, Tillots, MSD, Biogen, Amgen, Fresenius, Hospira, Pfizer, Celgene, Gilead, Boerhringer, Galapagos, Janssen and Takeda. Delphine Ley has received consultant fees from Sandoz and AbbVie. Thierry Paupard has received lecture/consultant fees from Abbvie, Amgen, Takeda, Janssen, Biogen, and Celltrion. Dominique Turck has received lecture fees from Sandoz. Nicolas Richard has received lecture/consultant fees from AbbVie and Takeda. The other authors state that they have no competing interests regarding this work to disclose., (© 2024 The Author(s).)

Background: Both vedolizumab and ustekinumab can be considered for the treatment of ulcerative colitis [UC], but head-to-head trials are lacking., Aim: We aimed to compare the effectiveness of vedolizumab and ustekinumab after anti-tumour necrosis factor [anti-TNF] failure in UC patients., Patients and Methods: In this multicentre study, we included consecutive adult patients with UC, with partial Mayo score >2 and prior anti-TNF exposure, treated with vedolizumab or ustekinumab between January 2019 and August 2022. Comparisons were performed using propensity score analyses [inverse probability of treatment weighting]., Results: Among a total of 293 patients included, 151 and 142 received vedolizumab and ustekinumab, respectively. After propensity score analysis, steroid-free clinical remission [SFCR] [partial Mayo score ≤2] was achieved at week 16 in 38.0% and 40.3% of patients treated with vedolizumab and ustekinumab, respectively (adjusted odds ratio [aOR] = 1.11, 95% confidence interval [0.39-3.13], p = 0.85). Rates of SFCR in patients exposed to one, two, and three lines of biologics/small molecules among patients treated with vedolizumab and ustekinumab were respectively 53.3% vs 62.1% [p = 0.52], 44.4% vs 33.8% [p = 0.52], and 2.6% vs 19.1% [p = 0.027]. Endoscopic remission [SFCR and endoscopic Mayo score ≤1] and histological remission [SFCR, endoscopic remission, and Nancy histological index ≤1] at week 16 were achieved in respectively 5.3% vs 17.5% (aOR = 3.77 [1.25-11.36], p = 0.018) and 2.1% vs 11.1% (aOR = 5.85 [1.47-23.30], p = 0.012) in the vedolizumab and ustekinumab groups. No difference regarding the risk of drug discontinuation between the two groups (aHR = 1.03 [0.51-2.08], p = 0.92) was observed. While no factor was identified for vedolizumab, primary failure to at least one biologic/small molecule (OR = 0.31 [0.11-0.82], p = 0.018) was significantly associated with a decreased rate of SFCR among patients treated with ustekinumab., Conclusion: While no difference in terms of short-term clinical remission was observed, ustekinumab appears to be more effective than vedolizumab in inducing endoscopic and histological remission at week 16 after failure of anti-TNFs in UC., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Introduction: Patients with inflammatory bowel disease (IBD) are at higher risk of thromboembolic events (TE). In pediatric-onset IBD, more data on incidence and risk factors of venous (VTE) and arterial events (ATE) at the population level are needed to guide thromboprophylaxis., Methods: All patients aged ≤ 16 years diagnosed with Crohn's disease (CD) or ulcerative colitis (UC) between 1988 and 2011 in the prospective EPIMAD population-based registry were followed until 2013. Every TE occurring during the follow-up period was included., Results: A total of 1,344 patients were included: 1,007 with CD and 337 with UC, and a median diagnosis age of 14.3 years. After a median follow-up of 8.3 years, 2 (0.15 %) ATE and 15 (1.1 %) VTE occurred at median age of 20.4 years. The global incidence rate of thromboembolic events was 1.32 per 1000 person-years. Periods of active disease (HR=8.4, p = 0.0002), the 3-month-period following surgery (HR=16.4, p = 0.0002) and hospitalization (HR=21.7, p < 0.0001) were found to be associated with an increased risk of VTE. A lower rate of VTE was found in patients treated with 5-aminosalicylates (HR=0.1, p = 0.002)., Conclusion: The risk of TE was low in this population. VTE were strongly associated with active disease, surgery and hospitalization., Competing Interests: Conflict of interest The authors declare the following conflict of interest: M.F. has received lecture/consultant fees from AbbVie, Ferring, Tillotts, MSD, Biogen, Amgen, Fresenius, Hospira, Sandoz, Pfizer, Celgene, Gilead, Boehringer, Galapagos, Janssen, and Takeda. C.D. has received consultant fees from AbbVie. N.R. has received lecture/consultant fees from AbbVie and Takeda. The other authors state that they have no competing interests regarding this work to disclose., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background and Aims: Epidemiological data regarding inflammatory bowel disease [IBD] are lacking, in particular for occupationally exposed populations. We investigated whether, among the entire French farm manager [FM] workforce, certain agricultural activities are more strongly associated with IBD than others., Methods: Nationwide, population-based, insurance claims and electronic health records from all FMs who worked at least once over the period 2002-2016 were used [n = 1 088 561, 69% males]. The outcome measure was the association between 26 farming activities and the risk of IBD, Crohn's disease [CD], and ulcerative colitis [UC], measured as hazard ratios [HRs], after adjusting for age, sex, pre-existing medical comorbidities, and farm location. The time to first chronic disease declaration was used as the underlying time scale. A model was generated for every activity and disease, using a reference group comprising all FMs who abstained from the specified activity from 2002 to 2016., Results: There were 1752 IBD cases, with 704 CD [40.2%] and 1048 UC [59.8%] cases, respectively. Elevated HRs were observed for fruit arboriculture [HR from 1.17 to 1.52] and dairy farming [HR from 1.22 to 1.46] for all IBD, in crop farming for CD only (HR = 1.26, 95% confidence interval [CI]: 1.06-1.49), and in shellfish farming [HR from 2.12 to 2.51] for both CD and IBD., Conclusions: Further research regarding specific farming activities and exposures likely to modify the microbiota [eg, pesticides, pathogens] is required to identify potential occupational risk factors [agricultural exposome] for IBD. Exposure to Mycobacterium avium subspecies paratuberculosis, Cryptosporidium, environmental toxins, micro/nanoplastics, and pesticides represents promising research avenues., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Introduction: It is still unclear whether Crohn's disease (CD) might be associated with diminished ovarian reserve (OvR) and factors influencing anti-Mullerian hormone (AMH) levels in CD are poorly known., Material and Methods: We conducted a comprehensive literature search of multiple electronic databases from inception to June 2022 to identify all studies reporting AMH levels or factors associated with diminished OvR in patients with CD., Results: Of the 48 studies identified in our search, eight (including 418 patients with CD) were finally included. The mean difference (95% confidence interval [CI]) in the AMH level between pooled CD patients and controls was -0.56 (-1.14 to 0.03) (p = 0.06). A history of CD-related surgery was not associated with a lower OvR (odds ratio, OR [95% CI] 1.34, [0.66-2.7]; p = 0.4). While disease activity and perianal disease seems associated with a low OvR, disease location (L2 vs. L1, OR [95% CI] = 95% CI [0.47-7.4]; p = 0.4) and L3 vs. L1 (OR [95% CI] = 1.44 [0.67-3.12]; p = 0.3), CD medication, and disease behavior were not., Conclusions: Our systematic review and meta-analysis did not identify a significantly low OvR in patients with CD. Contrary to CD-related surgery risk factor, active disease was associated lower AMH levels., (© 2024 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Epidemiological and translational data increasingly implicate environmental pollutants in inflammatory bowel disease (IBD). Indeed, the global incidence of IBD has been rising, particularly in developing countries, in parallel with the increased use of chemicals and synthetic materials in daily life and escalating pollution levels. Recent nationwide and ecological studies have reported associations between agricultural pesticides and IBD, particularly Crohn's disease. Exposure to other chemical categories has also been linked with an increased risk of IBD. To synthesise available data and identify knowledge gaps, we conducted a systematic review of human studies that reported on the impact of environmental pollutants on IBD risk and outcomes. Furthermore, we summarised in vitro data and animal studies investigating mechanisms underlying these associations. The 32 included human studies corroborate that heavy and transition metals, except zinc, air pollutants, per- and polyfluorinated substances, and pesticides are associated with an increased risk of IBD, with exposure to air pollutants being associated with disease-related adverse outcomes as well. The narrative review of preclinical studies suggests several overlapping mechanisms underlying these associations, including increased intestinal permeability, systemic inflammation and dysbiosis. A consolidated understanding of the impact of environmental exposures on IBD risk and outcomes is key to the identification of potentially modifiable risk factors and to inform strategies towards prediction, prevention and mitigation of IBD., Competing Interests: Competing interests: MF reports receiving lecture/consultant fees from Abbvie, Ferring, Tillots, MSD, Biogen, Amgen, Fresenius, Hospira, Sandoz, Pfizer, Bristol Myers Squibb, Celgene, Gilead, Boehringer, Eli Lilly, Nordic-Pharma, Arena, Galapagos, Janssen and Takeda. JFC reports receiving research grants from AbbVie, Janssen Pharmaceuticals and Takeda; receiving payment for lectures from AbbVie, Amgen, Allergan, Ferring Pharmaceuticals, Shire and Takeda; receiving consulting fees from AbbVie, Amgen, Arena Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb, Celgene Corporation, Eli Lilly, Ferring Pharmaceuticals, Galmed Research, Glaxo Smith Kline, Geneva, Iterative Scopes, Janssen Pharmaceuticals, Kaleido Biosciences, Landos, Otsuka, Pfizer, Prometheus, Sanofi, Takeda, TiGenix and hold stock options in Intestinal Biotech Development.MA reports consulting for Douglas Pharmaceutical., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

The Groupe d'Etude sur les Affections Inflammatoires Digestives (GETAID) was founded in Paris in 1983 by Professor R Modigliani and colleagues. From the beginning, the aim of this international (France, Belgium and Switzerland), multicentre, French-speaking group was to address clinical questions raised by patients or physicians in their daily practice or the inflammatory bowel diseases community, by focusing on clinical research on treatments through randomised controlled trials, prospective cohorts and cross-sectional studies, quantifying the severity of various facets of the disease when necessary for these studies. This approach very innovative has contributed to the advancement of knowledge in inflammatory bowel diseases by publishing more than 120 original articles in peer-reviewed journals throughout the GETAID 40-year history, most of them in top publications in gastroenterology and hepatology journals. In this paper, we will see what GETAID's contribution has been over the last four decades, review reasons for success and forthcoming challenges., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Several adalimumab preparations are now available for patients with inflammatory bowel disease (IBD). Comparative satisfaction and tolerability are unknown., Objectives: This study investigated IBD patient satisfaction with approved adalimumab biosimilars and their originator., Design: In this cross-sectional study, we included 941 consecutive adalimumab-treated patients with IBD across 45 centres affiliated with the Groupe d'Etude Therapeutique des Affections Inflammatoires du tube Digestif who completed a satisfaction questionnaire comprising four items each rated by a 10-point scale., Methods: The differences in responses were performed using a one-way analysis of variance followed by Tukey's honest significant difference test., Results: The most commonly used drugs at inclusion were Humira ® (436/941, 46.3%), Amgevita ® (177/941, 18.8%) and Hulio ® (105/941, 11.2%). The mean overall satisfaction rate with adalimumab was 8.5 (standard deviation 1.8). Overall satisfaction was significantly higher in patients treated with Humira (8.6 (1.5)), Hulio (8.6 (1.8)) or Amgevita (8.5 (1.4)) ( p  < 0.05). Satisfaction with the subcutaneous injection form was higher for patients treated with Yuflyma ® (9.0 (1.4)), Humira (8.9 (1.3)) and Hulio (8.9 (1.7)) ( p  < 0.05). A total of 299 patients (31.8%) described injection site reactions. In all, 223 patients (23.7%) reported being previously treated with another adalimumab of which (32/223, 14.3%) discontinued treatment due to side effects., Conclusion: In this real-world setting, patients with IBD had a high level of satisfaction with adalimumab treatment, with some differences in terms of overall satisfaction and satisfaction with the injection device., Competing Interests: B. Caron reports lecture and/or consulting fees from Abbvie, Amgen, Celltrion, Ferring, Galapagos, Janssen, Lilly and Takeda. P. Seksik received consulting fees from Takeda, Abbvie, Merck-MSD, Biocodex, Janssen, Amgen, Astellas and Pfizer and grants from Biocodex and Janssen. A. Buisson declares consulting fees from Abbvie, Amgen, Arena, Biogen, Celltrion Healthcare, CTMA, Galapagos, Janssen, MSD, Nexbiome, Pfizer, Roche, Takeda and Tillotts; lecture fees for Abbvie, Amgen, Biogen, Galapagos, Janssen, Mayoli-Spindler, MSD, Norgine, Pfizer, Roche, Takeda, Tillotts and Vifor Pharma; research grants from Abbvie, Celltrion Healthcare Janssen, Lilly, Pfizer and Takeda. P. Wils declares lecture and/or consulting fees from Abbvie, Biogen, Celltrion Ferring, Janssen, Pfizer, Lilly, Takeda and Amgen. G. Savoye reports travel from Janssen. C. Stefanescu declares lecture and/or consulting fees from Abbvie, Amgen, Biogen, Celltrion Ferring, Gilead, Janssen, Pfizer, Lilly, Takeda, Tillots. D. Laharie declares counselling, boards, transports or fees from Abbvie, Amgen, Biogen, Celltrion, Ferring, Galapagos, Janssen, Lilly, MSD, Pfizer, Prometheus, Roche, Takeda. L. Guillo declares consulting fees for Abbvie. V. Abitbol has received lecture fees from Amgen, Biogen, Mylan, Sandoz, Pfizer, Takeda, Janssen, Tillots, Gilead, Ferring. J. Bonnet reports fees from Galapagos, Celltrion Healthcare and Fresenius Kabi. R. Altwegg declares counselling, boards, transports or fees from Abbvie, Amgen, Biogen, Ferring, Janssen, MSD, Pfizer, Takeda, Tillotts. L. Vuitton declares lecture and/or consulting fees from Abbvie, Amgen, Viatris, MSD, Ferring, Celltrion, Galapagos, Takeda, Pfizer, Janssen, Lilly, Dr Falk pharma. D. Moussata reports lecture and/or consulting fees from Abbvie, Amgen, Galapagos, Janssen, Takeda, Sanofi, Fuji, Cellvizio. A. Bourreille reports lecture and/or consulting fees from AbbVie, Celltrion, Ferring, Galapagos, Janssen, Lilly, MSD, OSE Immunotherapeutics, Pfizer, Takeda, Tillots, Viatris. A. Biron reports no conflict of interest. C. Gilletta reports lecture and/or consulting fees from Abbvie, Amgen, Celltrion, Galapagos, Janssen, Pfizer and Takeda. M. Fumery has participated in advisory boards and as an educational speaker (personal fees) for AbbVie, Amgen, Biogen, Boehringer Ingelheim, Celgene, Celltrion, CTMA, Ferring, Fresenius, Galapagos, Janssen, MSD, Takeda, Tillotts, Pfizer, Sandoz and Viatris and has received research grants from Fresenius, Janssen and Pfizer. S. Nahon declares lecture and/or consulting fees from Abbvie, Amgen, Viatris, MSD, Ferring, Celltrion, Galapagos, Takeda, Pfizer, Janssen, Lilly, Ferring, Biogen. S. Nancey reports lecture and/or consulting fees from Abbvie, Amgen, Celltrion, Ferring, Galapagos, Janssen, Lilly, Takeda, Novartis and Pfizer. H. Camara declares no conflict of interest. L. Peyrin-Biroulet reports lecture and/or consulting fees from AbbVie, Adacyte, 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, Nordic Pharma, Novartis, OM Pharma, ONO Pharma, OSE Immunotherapeutics, Pandion Therapeutics, Par’Immune, Pfizer, Prometheus, Protagonist, Roche, Sanofi, Sandoz, Takeda, Theravance, Thermo Fisher, Tigenix, Tillots, Viatris, Vifor, Ysopia, Abivax, Samsung, Ventyx, Roivant and Vectivbio., (© The Author(s), 2024.)

Background: Data on infliximab efficacy in bio-exposed patients with ulcerative colitis (UC) are limited., Aims: To evaluate infliximab effectiveness and its predictors in UC patients with prior exposure to subcutaneous (SC) anti-TNF agent., Methods: In this multicenter retrospective study (8 centers), we included all consecutive UC patients with prior exposure to subcutaneous anti-TNF, starting infliximab for symptomatic UC, excluding acute severe colitis. Corticosteroid-free clinical remission (CFREM) was assessed at week 14 (W14) and W52 while endoscopic improvement (CFREM + endoscopic Mayo score≤1) was evaluated at W14., Results: Overall, 104 patients were included (pancolitis=54.8%, primary failure to subcutaneous anti-TNF=57.4%, concomitant immunosuppressant=53.8%, median partial Mayo score at baseline=7[5-8]). The rate of CFREM was 33.6% (35/104) at W14 and 40.4% (42/104) at W52. At W14, endoscopic improvement was achieved in 29.8%(31/104). In multivariable analysis, concomitant immunosuppressant was associated with higher rate of CFREM at W14(OR=2.83[1.06-7.54], p = 0.037) and W52(OR=2.68[1.16-6.22];p = 0.021), while primary failure to a previous subcutaneous anti-TNF agent led to lower rate of CFREM at W14 (OR=0.37[0.14-0.98], p = 0.046). After a median follow-up of 20.9 months[11.7-33.7]), 50.0%(52/104) patients had discontinued infliximab., Conclusion: Infliximab is an effective option in UC patients previously exposed to prior subcutaneous anti-TNF agent and should be used with concomitant immunosuppressant., (Copyright © 2024. Published by Elsevier Ltd.)

Introduction: Inflammatory bowel diseases (IBD) are frequently diagnosed between the ages of 20 and 40, i.e. the most fertile period for women. The potential impact of IBD on pregnancy is therefore a frequent issue., Study Objective: To determine the impact of disease activity during pregnancy on the obstetric prognosis of women with IBD., Methods: Gastroenterological and obstetric data were collected for patients for all consecutive patients with IBD and pregnancy followed up at Amiens University Hospital (Amiens, France) between 2007 and 2021. Obstetrics outcome of patients with and without active disease were compared., Results: One hundred patients were included (81 with Crohn's Disease for 198 pregnancies, 19 with Ulcerative Colitis for 37 pregnancies). Patients with active IBD (21 patients, 24 pregnancies) were more likely to be admitted to hospital during pregnancy (66.6, vs. 5.2% in the inactive IBD group; p < 0.001), to give birth prematurely (mean term: 36.77 weeks of amenorrhoea (WA) vs. 38.7 WA, respectively; p = 0.02) and to experience very premature delivery (before 32 WA: 12.5 vs. 1.4%, respectively; p = 0.02). Patients with active disease had a shorter term at birth (38.4 WA, vs. 39.8 WA in the inactive disease group; p < 0.0001), a lower birth weight (2707 g vs. 3129 g, respectively; p = 0.01) and higher caesarean section rate (54.2 vs. 16.9%, respectively; p = 0.03)., Conclusion: Women with IBD patients are at risk of pregnancy related complications, especially when IBD is active. Controlling disease activity at conception and close monitoring of the pregnancy is essential to improve both gastroenterological and obstetric outcome., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Endoscopy is still the gold, standard for assessing disease activity in Crohn's disease (CD). Its invasiveness, poor acceptability, and cost limit its use in the era of tight control and treat-to-target management. Fecal calprotectin (FC) and intestinal ultrasound (IUS) are non-invasive alternatives to colonoscopy to assess disease activity. We aimed to evaluate the performance of IUS and FC to assess mucosal healing in CD., Methods: All consecutive CD patients who underwent colonoscopy for mucosal healing assessment and IUS and/or FC within four weeks between September 2019 and April 2022 were included in a prospective cohort. The bowel-wall thickness (BWT) and color Doppler signal (CDS) were assessed for each segment. Endoscopic remission was defined by a CDEIS score < 3., Results: In total, 153 patients were included, of whom 122 showed endoscopic mucosal healing. Eighty-two (53.6 %) were female, the median was age 36 years (IQR, 28-46), and the median disease duration was 10 years (IQR, 4-19). The sensitivity (Se), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV) of a BWT < 3 mm to predict endoscopic mucosal healing were 56 %, 88 %, 95 %, and 36 %, respectively (patients misclassified as mucosal healing, 2.5 %). The best FC threshold (< 92.9 µg/g) provided similar results: 77 %, 89 %, 96 %, and 67 %, respectively (patients misclassified, 2.2 %). The association of an FC < 250 µg/g with a BWT < 3 mm and the absence of CDS increased the Sp and PPV: Se 58 %, Sp 95 %, PPV 97 %, VPN 43 %; patients misclassified, 1.3 %., Conclusion: Noninvasive evaluation of mucosal healing by IUS or calprotectin efficiently identifies patients with CD who have achieved endoscopic mucosal healing., Competing Interests: Declaration of competing interest CY: consultant and lecture fees from Abbvie, Takeda, Janssen, Amgen, and Galapagos MF: consultant and lecture fees from Abbvie, Takeda, Janssen, Amgen, Galapagos, Gilead, Biogen, Fresenius, Pfizer, Lilly, Celltrion, Ferring, Tillots, and Nordic Pharma VH: AAA, Merck KGaA, Amgen, Servier, Deciphera, Ipsen, and Pierre Fabre The other authors have nothing to declare., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Background: The development of noninvasive markers to assess mucosal healing in ulcerative colitis (UC) is essential in the treat-to-target era. The aim of this study was to evaluate the performance of intestinal ultrasound (IUS), fecal calprotectin (FC), and their combination to assess mucosal healing in UC patients., Methods: All consecutive patients between January 2021 and September 2022 with UC who underwent a complete colonoscopy and IUS and/or an FC test within 4 weeks were included in a prospective cohort. Bowel wall thickness (BWT) and the color Doppler signal (CDS) were assessed for each segment. Endoscopic mucosal healing was defined by a Mayo score of 0 to 1., Results: A total of 61 patients were included, of whom 79% showed endoscopic healing (26 Mayo 0 and 11 Mayo 1). Among the patients, 16 (27.6%) of 58 had a BWT <3 mm, and 41 (70.7%) of 58 had no CDS. The sensitivity, specificity, positive predictive value, and negative predictive value of a BWT <3 mm to predict endoscopic mucosal healing were 37%, 77%, 72%, and 44%, respectively. The association of FC <150 µg/g, a BWT <3 mm, and a CDS = 0 increased the specificity and positive predictive value (sensitivity 33%, specificity 94%, positive predictive value 89%, negative predictive value 48%). The combination of a normal IUS, no rectal bleeding, and an FC <172 µg/g identified all patients with mucosal healing., Conclusion: The combination of IUS and FC is effective in identifying mucosal healing in UC. Noninvasive evaluation of mucosal healing is possible for most UC patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background and Aims: While the occurrence of colonic stricture in Crohn's disease (CD) always raises concerns about the risk of cancer, the neoplastic risk associated with its stricture remains poorly known., Methods: All consecutive patients with colorectal stricture complicating CD in 3 academic centers between 1993 and 2022 were included in a retrospective cohort. We collected clinical, endoscopic, surgical, and pathology data and information on outcomes. Factors associated with neoplastic stricture were investigated by logistic regression., Results: A total of 88 patients (median age, 25 [interquartile range {IQR}, 19-37] years and median disease duration 12 [4-19] years) with 96 colorectal strictures were included. Strictures were nonpassable by the scope in 61.4% (n = 54) of cases, 70.5% (n = 62) were ulcerated, and 62.5% (n = 55) were symptomatic. Colonic resection and endoscopic balloon dilatation were needed in 47.7% (n = 42) and 28.6% (n = 12) of patients, respectively. After a median follow-up of 21.5 months (IQR [5.5-46.5]), 7 (8%) patients were diagnosed with neoplasia at the colonic stricture site (colonic adenocarcinoma, n = 5; neuroendocrine carcinoma, n = 1; and B-cell lymphoproliferative neoplasia, n = 1), with a median stricture duration at colorectal neoplasia diagnosis of 0 month (IQR [0.0-5.5]). While neoplastic strictures were diagnosed in older patients (58 vs 39 years), with longer disease duration (18 vs 11 years) and frequent obstructive symptoms (57.1% vs 11.1%), no patient-related or stricture-related factor was associated with neoplastic stricture in multivariate analysis., Conclusion: Eight percent of patients with colonic stricture complicating CD developed colorectal cancer. Colorectal cancer and stricture were often diagnosed at the same time and we did not report malignant stricture after 1 year of follow-up., (© 2024 The Authors.)

Background: Acute gastrointestinal bleeding (AGIB) is common in older patients but the use of iron in this context remains understudied., Aims: This study aimed to evaluate prospectively the efficacy of ferric carboxymaltose to treat anaemia in older patients after AGIB., Methods: This randomised double-blinded placebo-controlled clinical trial was conducted in 10 French centres. Eligible patients were 65 years or more, had controlled upper or lower gastrointestinal bleeding and a haemoglobin level of 9-11 g/dl. Patients were randomly assigned, in a 1:1 ratio, to receive either one intravenous iron injection of ferric carboxymaltose or one injection of saline solution. The primary endpoint was the difference in haemoglobin level between day 0 and day 42. Secondary endpoints were treatment-emergent adverse events, serious adverse events, rehospitalisation and improvement of quality of life (QOL) at day 180., Results: From January 2013 to January 2017, 59 patients were included. The median age of patients was 81.9 [75.8, 87.3] years. At day 42, a significant difference in haemoglobin level increase was observed (2.49 g/dl in the ferric carboxymaltose group vs. 1.56 g/dl in the placebo group, P = 0.02). At day 180, QOL, measured on European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, improved by 10.5 points in the ferric carboxymaltose group and by 8.2 points in the placebo group (P = 0.56). Rates of adverse events and rehospitalisation were similar in the two groups., Conclusions: Intravenous iron seems safe and effective to treat anaemia in older patients after AGIB and should be considered as a standard-of-care treatment. ClinicalTrials.gov (NCT01690585)., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Competing Interests: MF has received consulting or lecture fees from AbbVie, Amgen, Arena, Biogen, Celltrion, CTMA, Galapagos, Janssen, MSD, Pfizer, Takeda, Tillotts, MSD, Gilead, Fresenius, Celgene, Sandoz, and Ferring. AB has received consulting fees from AbbVie, Amgen, Arena, Biogen, Celltrion, CTMA, Fresenius-Kabi, Galapagos, Janssen, MSD, Nexbiome, Pfizer, Roche, Takeda, and Tillott; lecture fees from AbbVie, Amgen, Biogen, Fresenius-Kabi, Galapagos, Janssen, Mayoli-Spindler, MSD, Norgine, Pfizer, Roche, Takeda, Tillotts, and Vifor Pharma; and research grants from AbbVie, Celltrion, Janssen, Lilly, Pfizer, and Takeda.

The REMSWITCH study recently demonstrated that switching from intravenous (IV) to subcutaneous (SC) infliximab (IFX) is feasible and well-accepted leading to a low risk of relapse in patients with inflammatory bowel disease (IBD). 1 Because the doses of IV IFX depend on patients' weight contrary to SC IFX, whether the switch is also feasible in patients with IBD suffering from obesity remains questionable., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: While the efficacy of tofacitinib to induce and maintain clinical and endoscopic remission is well established in ulcerative colitis (UC), little is known about its efficacy to induce histological remission., Methods: We conducted a retrospective multicentric cohort study. UC patients ≥ 16 years treated by tofacitinib in whom histological activity has been evaluated before and after induction were eligible. The primary endpoint was the histological remission at the end of induction, assessed by the Nancy index and the epithelial neutrophilic infiltrate., Results: A total of 42 patients with UC (93% previously exposed to an anti-TNF and 81% to vedolizumab) were included between July 2018 and April 2022 and were followed for a median duration of 84 weeks [IQR, 35-134]. At the end of induction period (whether prolonged or not), 19% and 24% of patients achieved histological remission, using the Nancy index and the epithelial neutrophilic infiltrate, respectively. Survival without tofacitinib discontinuation was significantly longer in patients without epithelial neutrophilic infiltrate at the end of induction (whether prolonged or not) compared with patients with epithelial neutrophilic infiltrate (p = 0.036)., Conclusion: Tofacitinib induced histological remission in one fifth to one quarter of patients with UC who have previously failed anti-TNF or/and vedolizumab after induction (whether prolonged or not)., Competing Interests: Conflict of interests S Vieujean lecture and/or consulting fees from Abbvie, Ferring, Janssen, Takeda. D Laharie counselling, boards, transports and/or fees from Abbvie, Biogaran, Biogen, Ferring, HAC-pharma, Janssen, MSD, Novartis, Pfizer, Prometheus, Roche, Takeda, Theradiag, Tillots. A Buisson received consulting fees from AbbVie, Amgen, Arena, Biogen, Celltrion Healthcare, CTMA, Galapagos, Janssen, MSD, Nexbiome, Pfizer, Roche, Takeda, and Tillotts; and lecture fees from AbbVie, Amgen, Biogen, Galapagos, Janssen, Mayoli-Spindler, MSD, Norgine, Pfizer, Roche, Takeda, Tillotts, and Vifor Pharma. X Roblin served as a speaker, a consultant, and/or an advisory board member for MSD, Pfizer, Celltrion, Janssen, Takeda, AbbVie, Amgen, Biogen, Galapagos, Roche, and Theradiag. M Fumery declares financial support from Abbvie, MSD, Ferring, Boehringer, Pfizer, Takeda, Biogen, Amgen, Gilead, Sandoz, Celgene, Galapagos, Janssen, and Tillots Pharma. S Nancey declares lecture and/or consulting fees from Abbvie, Janssen, Ferring, Takeda, Amgen, Biogen, Novartis, Celltrion, Pfizer, MEDAC, NORDIC Pharma, Maat Pharma. P Wils declares lecture and/or consulting fees from Abbvie, Ferring, Biogen, Janssen, Celltrion, Takeda. R Altwegg declares counselling, boards, transports or fees from Abbvie, Amgen, Biogen, Ferring, Janssen, MSD, Pfizer, Takeda, Tillotts. L Seidel has no conflict of interest. B Caron declares lecture and/or consulting fees from Abbvie, Amgen, Celltrion, Ferring, Janssen, Lilly, and Takeda. L Peyrin-Biroulet declares consulting fees from AbbVie, Adacyte, 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, Nordic Pharma, Novartis, OM Pharma, ONO Pharma, OSE Immunotherapeutics, Pandion Therapeutics, Par'Immune, Pfizer, Prometheus, Protagonist, Roche, Sanofi, Sandoz, Takeda, Theravance, Thermo Fisher, Tigenix, Tillots, Viatris, Vifor, Ysopia, Abivax, Samsung, Ventyx, Roivant, Vectivbio., (Copyright © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Although ulcerative proctitis [UP] can dramatically impair quality of life, treatment efficacy has been poorly investigated in UP as it was historically excluded from phase 2/3 randomised controlled trials in ulcerative colitis. Our aim was to assess the effectiveness and safety of tofacitinib for the treatment of UP., Methods: We conducted a retrospective, multicentre study in 17 GETAID centres, including consecutive patients with UP treated with tofacitinib. The primary endpoint was steroid-free remission between Week 8 and Week 14, defined as a partial Mayo score of 2 [and no individual subscore above 1]. Secondary outcomes included clinical response and steroid-free remission after induction and at 1 year., Results: All the 35 enrolled patients previously received anti-tumour necrosis factor [TNF] therapy and 88.6% were exposed to at least two lines of biologics. At baseline, the median partial Mayo score was 7 (intequartile range [IQR] [5.5-7]). After induction [W8-W14], 42.9% and 60.0% of patients achieved steroid-free remission and clinical response, respectively. At 1 year, the steroid-free clinical remission and clinical response rates were 39.4% and 45.5%, respectively, and 51.2% [17/33] were still receiving tofacitinib treatment. Survival without tofacitinib withdrawal was estimated at 50.4% (95% confidence interval [CI] [35.5-71.6]) at 1 year. Only a lower partial Mayo at baseline was independently associated with remission at induction (0dds ratio [OR] = 0.56 for an increase of 1, (95% CI [0.33-0.95], p = 0.03). Five [14.3%] adverse events were reported, with one leading to treatment withdrawal [septic shock secondary to cholecystitis]., Conclusion: Tofacitinib may offer a therapeutic option for patients with refractory UP., (© The Author(s) 2023. 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.)

Competing Interests: MF declares consulting or lecture fees from AbbVie, Amgen, Arena, Biogen, Celtrion, CTMA, Galapagos, Janssen, MSD, Pfizer, Takeda, Tillotts, MSD, Gilead, Fresenius, Celgene, Sandoz, and Ferring. AB declares consulting fees from AbbVie, Amgen, Arena, Biogen, Celtrion, CTMA, Fresenius-Kabi, Galapagos, Janssen, MSD, Nexbiome, Pfizer, Roche, Takeda and Tillotts; lecture fees from AbbVie, Amgen, Biogen, Fresenius-Kabi Galapagos, Janssen, Mayoli-Spindler, MSD, Norgine, Pfizer, Roche, Takeda, Tillotts, and Vifor Pharma; and research grants from AbbVie, Celltrion, Janssen, Lilly, Pfizer, and Takeda.

Background: The long-term risk of relapse after switching from intravenous (IV) to subcutaneous (SC) infliximab remains unknown in inflammatory bowel disease (IBD)., Aims: To assess the long-term effectiveness and acceptability of switching from IV to SC infliximab in patients with IBD treated with or without an intensified IV regimen., Methods: We extended the follow-up of the REMSWITCH study including patients with IBD in clinical remission who were switched from IV to SC infliximab (120 mg/2 weeks). Relapse was defined as clinical relapse or faecal calprotectin increase ≥150 μg/g compared to baseline., Results: After median follow-up of 18 [15-20] months, among 128 patients, rates of relapse were 13.8% (8/58), 18.4% (7/38), 35.3% (6/17) and 86.7% (13/15) at last follow-up (p < 0.001), in those receiving 5 mg/kg/8 weeks, 10 mg/kg/8 weeks, 10 mg/kg/6 weeks and 10 mg/kg/4 weeks at baseline, respectively. Among relapsing patients, dose escalation led to clinical remission in 82.1% (23/28). In multivariable analyses, factors associated with higher risk of relapse were IV infliximab 10 mg/kg/4 weeks (OR = 61.0 [6.1-607.0], p < 0.001) or 10 mg/kg/6 weeks (OR = 4.7 [1.1-20.2], p = 0.017), and decreased (OR = 5.6 [1.5-20.3], p = 0.004) or stable (OR = 5.0 [1.6-15.0], p = 0.009) serum levels of infliximab between baseline and first post-switch visit. Acceptability was improved at 6 months and did not decrease over time (6.9 ± 1.6 before the switch vs. 8.8 ± 1.3 at 6 months and 8.8 ± 1.3 at last follow-up; p < 0.001). No severe adverse events were reported., Conclusions: Switching from IV to SC infliximab 120 mg every other week is safe and well accepted leading to low long-term risk of relapse. Tight monitoring and dose escalation should be recommended for patients receiving 10 mg/kg/6 weeks and 4 weeks, respectively., (© 2023 John Wiley & Sons Ltd.)

Background: Anti-TNF agents are the first biologic treatment option in inflammatory bowel disease (IBD). The long-term effectiveness of this strategy at the population level is poorly known, particularly in pediatric-onset IBD., Methods: All patients diagnosed with Crohn's disease (CD) or ulcerative colitis (UC) before the age of 17 between 1988 and 2011 in the EPIMAD population-based registry were followed retrospectively until 2013. Among patients treated with anti-TNF, the cumulative probabilities of anti-TNF failure defined by primary failure, loss of response (LOR) or intolerance were evaluated. Factors associated with anti-TNF failure were investigated by a Cox model., Results: Among a total of 1,007 patients with CD and 337 patients with UC, respectively 481 (48%) and 81 (24%) were treated with anti-TNF. Median age at anti-TNF initiation was 17.4 years (IQR, 15.1-20.9). Median duration of anti-TNF therapy was 20.4 months (IQR, 6.0-59.9). In CD, the probability of failure of 1st line anti-TNF at 1, 3 and 5 years was respectively 30.7%, 51.3% and 61.9% for infliximab and 25.9%, 49.3% and 57.7% for adalimumab (p = 0.740). In UC, the probability of failure of 1st line anti-TNF therapy was respectively 38.4%, 52.3% and 72.7% for infliximab and 12.5% for these 3 timepoints for adalimumab (p = 0.091). The risk of failure was maximal in the first year of treatment and LOR was the main reason for discontinuation. Female gender was associated with LOR (HR, 1.48; 95%CI 1.02-2.14) and with anti-TNF withdrawal for intolerance in CD (HR, 2.31; 95%CI 1.30-4.11) and disease duration (≥ 2 y vs. < 2 y) was associated with LOR in UC (HR, 0.37; 95%CI 0.15-0.94) in multivariate analysis. Sixty-three (13.5%) patients observed adverse events leading to termination of treatment (p = 0.57). No death, cancer or tuberculosis was observed while the patients were under anti-TNF treatment., Conclusion: In a population-based study of pediatric-onset IBD, about 60% in CD and 70% in UC experienced anti-TNF failure within 5 years. Loss of response account for around two-thirds of failure, both for CD and UC., Competing Interests: Conflict of interest MF has received lecture/consultant fees from Abbvie, Ferring, Tillots, MSD, Biogen, Amgen, Fresenius, Hospira, Sandoz, Pfizer, Celgene, Gilead, Boehringer, Galapagos, Janssen and Takeda. CD has received consultant fees from Abbvie. PW: none DL has received lecture/consultant fees from Abbvie and Sandoz. The other authors state that they have no competing interests regarding this work to disclose., (Copyright © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: SB5 is an EMA-approved adalimumab biosimilar, having demonstrated bioequivalence, equivalent efficacy, and similar safety and immunogenicity to the reference product., Aims: Describe patient training and satisfaction using patient-reported outcome measures (PROMs) and assess their impact on 12-month persistence on SB5., Methods: The observational PERFUSE study included 318 Crohn's disease (CD) patients and 88 ulcerative colitis (UC) patients in 27 sites across France between October 2018 and December 2020. PROMs were collected at 1-month post-baseline using an online questionnaire (ePRO) designed with patient associations. Treatment persistence was collected during routine visits (up to 15 months post-initiation). Results are presented by prior experience with subcutaneous biologics and training in proper use of the injection device., Results: 57.1% (n = 145) and 44.1% (n = 67) of naïve and pre-treated patients, respectively, answered the ePRO. Naïve patients were offered training more often (86.9% vs 31.3% respectively, p < 0.05), with disparities between sites. All subgroups' satisfaction scores were high. 12-month persistence on SB5 was significantly higher for respondents than for non-respondents (68.0% [60.9; 74.1] vs 52.3% [44.5; 59.6]; p < 0.05) and in patients with a better perception of their illness (OR=1.02, [1.0; 1.05]; p < 0.05)., Conclusions: Early patient questionnaires may be useful to identify patients at higher risk of treatment discontinuation., (Copyright © 2023. Published by Elsevier Ltd.)

Cardiovascular and thromboembolic risks are increasing in the population as a whole and therefore also in inflammatory bowel disease (IBD) patients. Obesity is a worldwide challenge also affecting the IBD population, and a causal association with Crohn's disease may exist. IBD itself, particularly when active, is also associated with a significant risk of thromboembolic and cardiovascular events such as myocardial infarction and stroke. Cardiovascular risk is also a significant consideration when using Janus kinase (JAK) inhibitors and sphingosine 1 phosphate (S1P) receptor modulators to treat IBD. JAK inhibitors - such as tofacitinib - are associated with several cardiovascular and venous thromboembolic risks, including hypertension and alterations in lipid profiles - specifically, increased LDL cholesterol and triglycerides - which may contribute to atherosclerosis and cardiovascular disease. S1P receptor modulators pose a slightly different set of cardiovascular risks. Initially, these drugs can cause transient bradycardia and atrioventricular (AV) block, leading to bradycardia. Moreover, they may induce QT interval prolongation, which increases the risk of life-threatening arrhythmias such as torsades de pointes. Some patients may also experience hypertension as a side effect. In this context, IBD healthcare providers need to be alert to the assessment of cardiovascular risk - particularly as cardiovascular events appear to be confined to specific patient groups with pre-existing risk factors. In addition, the potential for S1P modulator drug interactions requires a higher level of vigilance in patients with polypharmacy compared to biologics. Cardiovascular risk is not static, and updated assessment will need to become part of the routine in many IBD units., (© 2023 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

Competing Interests: LJM: Co-Founder of A-TRACT device & co.CY: consultant and lectures for Abbvie, Takeda, Jansen, Amgen, Galapagos.JR: Honorary for Training sessions in endoscopy and endoscopic resection for Olympus, Cook Medical, Co-Founder of A-TRACT device & co.MP: Honorary for Training sessions in endoscopy and endoscopic resection for Olympus, Cook Medical, Boston scientific, Pentax Medical. Co-Founder of A-TRACT device & co.Honorary for Training sessions in endoscopic characterization with Norgine, Provepharm. Uegw invitation by AlfaSigma. Patent of our institution Hospices civils de Lyon for IPEFIX device.JJ: ESD training sessions: Olympus, Fuji, Erbe, Pentax, lumendi. Lectures: Abbvie, Janssen, norgine. Co-Founder of A-TRACT device & co.

Background & Aims: The management of intra-abdominal abscesses complicating Crohn's disease (CD) is challenging, and surgery with delayed intestinal resection is often recommended. The aims of this study were to estimate the success rate of adalimumab (ADA) in patients with CD with an intra-abdominal abscess resolved without surgery, and to identify predictive factors for success., Methods: A multicenter, prospective study was conducted in biologic-naïve patients with CD with resolved intra-abdominal abscess treated with ADA with a 2-year follow-up. The primary endpoint was ADA failure at week (W) 24 defined as a need for steroids after W12, intestinal resection, abscess recurrence, and clinical relapse. Secondary post-hoc endpoint was the long-term success defined as the survival without abscess relapse or intestinal resection at W104. The factors associated with ADA failure at W24 and W104 were identified using a logistic and a Cox regression, respectively., Results: From April 2013 to December 2017, 190 patients from 27 GETAID centers were screened, and 117 were included in the analysis. Fifty-eight patients (50%) were male, and the median age at baseline was 28 years. At W24, 87 patients (74%; 95% confidence interval [CI], 65.5%-82.0%; n = 117) achieved ADA success. Among the 30 patients with ADA failure, 15 underwent surgery. At W104, the survival rate without abscess recurrence or surgery was 72.9% (95% CI, 62.1%-79.8%; n = 109). Abscess drainage was significantly associated with ADA failure at W24 (odds ratio, 4.18; 95% CI, 1.06-16.5; P =0 .043). Disease duration (hazard ratio [HR], 1.32; 95% CI, 1.09-1.59; P = .008), abscess drainage (HR, 5.59; 95% CI, 2.21-14.15; P = .001), and inflammatory changes in mesenteric fat (HR, 0.4; 95% CI, 0.17-0.94; P = .046) were significantly associated with ADA failure at W104., Conclusion: Provided that the abscess was carefully managed before initiating medical treatment, this study showed the high efficacy of ADA in the short and long term in biologic-naïve patients with CD complicated by an intra-abdominal abscess., Clinicaltrials: gov, Number: NCT02856763., (Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Introduction: There is debate over the impact of residual microscopic disease after ileocecal resection in Crohn's disease (CD) to predict recurrence. We conducted a meta-analysis to evaluate the impact of positive histological margins and plexitis after ileocecal resection on the risk of postoperative recurrence., Methods: Using a systematic search, we identified. 30 studies evaluating the impact of inflammatory margins on CD recurrence. The primary outcome was the postoperative clinical recurrence and secondary outcomes were surgical, and endoscopic recurrence. We performed random-effects meta-analysis and estimated odds ratio (OR) and 95% CIs., Results: Thirty studies were analyzed, seven focused on myenteric plexitis, six on submucosal plexitis and twenty-three on positive margins. Inflammatory margins were associated with a higher rate of clinical and surgical recurrences: respectively 14 studies - OR 2.38; 95% CI, 1.54 - 3.68- I2 = 68.2%, Q test-p = 0.0003 and 8 studies - OR, 1.52; 95% CI, 1.07-2.16 - I2 =0%; Q test-p = 0.43. The presence of myenteric plexitis was associated with a higher rate of clinical recurrence (4 studies- OR, 1.60; 95%CI, 1.12-2.29; I2= 0%, Q-test-p = 0.61), and of endoscopic recurrence (4 studies - OR, 4.25; 95%CI; 2.06-8.76; I2= 0%, Q test-p = 0.97). Submucosal plexitis was not associated with an increased risk of endoscopic recurrence (4 studies - OR, 0.94; 95%CI; 0.58-1.52; I2= 0%, Q test-p = 0.79)., Conclusion: Inflammatory margins and/or plexitis were associated with postoperative recurrence after ileocecal resection for CD. These elements should be taken into account in future algorithm for prevention of postoperative recurrence., Competing Interests: Conflict of interest CS: Research grants from AbbVie and Janssen CY: Galapagos, Abbvie, Takeda, Ferring MF: Abbvie, Ferring, MSD, Janssen, Takeda, Tillots, Pfizer, Gilead, Celgene, Galapagos, Biogen, Amgen, Viatris, Fresenius, and Boehringer. No conflict to declare for other authors, (Copyright © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: The identification of patients at high risk of a disabling disease course would be invaluable in guiding initial therapy in Crohn's disease (CD). Our objective was to evaluate a combination of clinical, serological, and genetic factors to predict complicated disease course in pediatric-onset CD., Methods: Data for pediatric-onset CD patients, diagnosed before 17 years of age between 1988 and 2004 and followed more than 5 years, were extracted from the population-based EPIMAD registry. The main outcome was defined by the occurrence of complicated behavior (stricturing or penetrating) and/or intestinal resection within the 5 years following diagnosis. Lasso logistic regression models were used to build a predictive model based on clinical data at diagnosis, serological data (ASCA, pANCA, anti-OmpC, anti-Cbir1, anti-Fla2, anti-Flax), and 369 candidate single nucleotide polymorphisms., Results: In total, 156 children with an inflammatory (B1) disease at diagnosis were included. Among them, 35% (n = 54) progressed to a complicated behavior or an intestinal resection within the 5 years following diagnosis. The best predictive model (PREDICT-EPIMAD) included the location at diagnosis, pANCA, and 6 single nucleotide polymorphisms. This model showed good discrimination and good calibration, with an area under the curve of 0.80 after correction for optimism bias (sensitivity, 79%, specificity, 74%, positive predictive value, 61%, negative predictive value, 87%). Decision curve analysis confirmed the clinical utility of the model., Conclusions: A combination of clinical, serotypic, and genotypic variables can predict disease progression in this population-based pediatric-onset CD cohort. Independent validation is needed before it can be used in clinical practice., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: We evaluated the impact of immunosuppressants (IS) and antitumor necrosis factor (TNF) introduction on long-term outcomes of ulcerative colitis (UC) in a large population-based pediatric-onset cohort., Methods: All patients included in the EPIMAD registry with a diagnosis of UC made before the age of 17 years between 1988 and 2011 were followed up retrospectively until 2013. Medication exposure and disease outcomes were compared between 3 diagnostic periods: 1988 to 1993 (period [P] 1; pre-IS era), 1994 to 2000 (P2; pre-anti-TNF era), and 2001 to 2011 (P3; anti-TNF era)., Results: A total of 337 patients (female, 57%) diagnosed with UC were followed up during a median duration of 7.2 years (interquartile range 3.8-13.0). The IS and anti-TNF exposure rates at 5 years increased over time from 7.8% (P1) to 63.8% (P3) and from 0% (P1) to 37.2% (P3), respectively. In parallel, the risk of colectomy at 5 years decreased significantly over time (P1, 17%; P2, 19%; and P3, 9%; P = 0.045, P -trend = 0.027) and between the pre-anti-TNF era (P1 + P2, 18%) and the anti-TNF era (P3, 9%) ( P = 0.013). The risk of disease extension at 5 years remained stable over time (P1, 36%, P2, 32%, and P3, 34%; P = 0.31, P -trend = 0.52) and between the pre-anti-TNF era (P1 + P2, 34%) and the anti-TNF era (P3, 34%) ( P = 0.92). The risk of flare-related hospitalization at 5 years significantly increased over time (P1, 16%; P2, 27%; P3, 42%; P = 0.0012, P -trend = 0.0006) and between the pre-anti-TNF era (P1 + P2, 23%) and the anti-TNF era (P3, 42%) ( P = 0.0004)., Discussion: In parallel with the increased use of IS and anti-TNF, an important decline in the risk of colectomy in pediatric-onset UC was observed at the population level., (Copyright © 2023 by The American College of Gastroenterology.)

Background: Fatigue is commonly reported by patients with inflammatory bowel disease [IBD], but the determinants of IBD-related fatigue have yet to be determined., Aims: To identify the factors associated with fatigue in a large population of patients with IBD., Patients and Methods: Fatigue and nine other IBD-related disability dimensions were assessed in a cohort of 1704 consecutive patients with IBD using the IBD-disk questionnaire in a cross-sectional survey of 42 French and Belgian centres. Fatigue and severe fatigue were defined as energy subscores >5 and >7, respectively. Determinants of fatigue were assessed using univariate and multivariate analyses (odds ratios [ORs] are provided with 95% confidence intervals)., Results: The prevalence rates of fatigue and severe fatigue were 54.1% and 37.1%, respectively. Both fatigue and severe fatigue were significantly higher in patients with active disease than in patients with inactive disease [64.9% vs 44.7% and 47.4% vs 28.6%, respectively; p < 0.001 for both comparisons]. In the multivariate analysis stratified by age, sex, type of IBD and IBD activity, fatigue was associated with age >40 years (OR = 0.71 [0.54-0.93]), female sex (OR = 1.48 [1.13-1.93]) and IBD-related sick leave (OR = 1.61 [1.19-2.16]), and joint pain (OR = 1.60 [1.17-2.18]), abdominal pain (OR = 1.78 [1.29-2.45]), regulating defecation (OR = 1.67 [1.20-2.32]), education and work (OR = 1.96 [1.40-2.75]), body image (OR = 1.38 [1.02-1.86]), sleep (OR = 3.60 [2.66-4.88]) and emotions (OR = 3.60 [2.66-4.88]) subscores >5., Conclusion: Determinants of fatigue are not restricted to IBD-related factors but also include social factors, sleep and emotional disturbances, thus supporting a holistic approach to IBD patient care., (© The Author(s) 2023. 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.)

Introduction: Anal ulcerations are frequently observed in Crohn's disease (CD). However, their natural history remains poorly known, especially in pediatric-onset CD., Methods: All patients with a diagnosis of CD before the age of 17 years between 1988 and 2011 within the population-based registry EPIMAD were followed retrospectively until 2013. At diagnosis and during follow-up, the clinical and therapeutic features of perianal disease were recorded. An adjusted time-dependent Cox model was used to evaluate the risk of evolution of anal ulcerations toward suppurative lesions., Results: Among the 1,005 included patients (females, 450 [44.8%]; median age at diagnosis 14.4 years [interquartile range 12.0-16.1]), 257 (25.6%) had an anal ulceration at diagnosis. Cumulative incidence of anal ulceration at 5 and 10 years from diagnosis was 38.4% (95% confidence interval [CI] 35.2-41.4) and 44.0% (95% CI 40.5-47.2), respectively. In multivariable analysis, the presence of extraintestinal manifestations (hazard ratio [HR] 1.46, 95% CI 1.19-1.80, P = 0.0003) and upper digestive location (HR 1.51, 95% CI 1.23-1.86, P < 0.0001) at diagnosis were associated with the occurrence of anal ulceration. Conversely, ileal location (L1) was associated with a lower risk of anal ulceration (L2 vs L1 HR 1.51, 95% CI 1.11-2.06, P = 0.0087; L3 vs L1 HR 1.42, 95% CI 1.08-1.85, P = 0.0116). The risk of fistulizing perianal CD (pCD) was doubled in patients with a history of anal ulceration (HR 2.00, 95% CI 1.45-2.74, P < 0.0001). Among the 352 patients with at least 1 episode of anal ulceration without history of fistulizing pCD, 82 (23.3%) developed fistulizing pCD after a median follow-up of 5.7 years (interquartile range 2.8-10.6). In these patients with anal ulceration, the diagnostic period (pre vs biologic era), exposure to immunosuppressants, and/or anti-tumor necrosis factor did not influence the risk of secondary anoperineal suppuration., Discussion: Anal ulceration is frequent in pediatric-onset CD, with nearly half of patients presenting with at least 1 episode after 10 years of evolution. Fistulizing pCD is twice as frequent in patients with present or past anal ulceration., (Copyright © 2023 by The American College of Gastroenterology.)

Objectives: The aim of the study was to provide an overview of the practices of French general dentists (GDs) and specialists (SDs) concerning the management of patients with inflammatory bowel diseases (IBDs), rheumatic inflammatory diseases (IRDs), and vasculitis on biologic disease-modifying antirheumatic drugs (bDMARDs), conventional DMARDs, or immunosuppressants (ISs)., Materials and Methods: An online national cross-sectional survey with 53 questions was developed by a multidisciplinary team including rheumatologists, gastroenterologists and dentists based on their clinical experience. It was refined following a test with nine dentists in private practice and in hospital before being disseminated to the members of French scientific societies and colleges of dentistry teachers over 3 months. Responses of general dentists versus specialists were compared with respect to their experience in managing patients with IRDs or IBDs, knowledge/training, type of invasive procedure performed, management of medical treatment, perioperative oral-care protocols, and frequency of postoperative complications after invasive dental care procedures., Result: In total, 105 practitioners fully completed the survey (participation rate 11.1%). SDs more frequently performed invasive surgical procedures and were more aware of the recommendations of learned societies than GDs. They encountered more post-operative complications for patients on bDMARDs. For both SDs and GDs, most patients were managed without stopping treatment and pre- and postoperative antibiotics were prescribed to more than 75% of patients. When medical treatment was stopped, the decision was made by the prescribing physician., Conclusion: Complications were reported more frequently by SDs when highly invasive procedures were performed on patients under active drug therapy. Certain common procedures, such as scaling and root planing, appear to be safe, regardless of treatment management. However, adapted guidelines for the practice of dentistry are needed to standardize the management of patients on bDMARDS, conventional DMARDs, or ISs., Clinical Relevance: French dentists perform a wide range of oral procedures on patients on bDMARDS, conventional DMARDs, or ISs under antibiotic coverage and antiseptic mouthwashes. SDs reported more postoperative complications after extensive invasive procedures for patients under active drug therapy, despite their greater knowledge of recommendations on how to manage such patients., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background and Aims: We assessed the effectiveness of switching from intravenous to subcutaneous infliximab in patients with inflammatory bowel diseases (IBDs) treated with or without intensified intravenous regimen., Methods: In this multicenter observational study, IBD patients in clinical remission (partial Mayo score ≤2 or Harvey-Bradshaw index ≤4) were switched to a unique dose of subcutaneous infliximab (120 mg every other week). Pharmacological and biological data were collected at baseline, visit 1 (4-8 weeks postswitch), visit 2 (8-16 weeks postswitch), and visit 3 (16-24 weeks postswitch). Relapse was defined as clinical relapse or fecal calprotectin increase ≥150 μg/g compared with baseline., Results: Among 184 eligible patients, 72.3% (n = 133 of 184) agreed to switch to subcutaneous infliximab. At visit 3, a relapse occurred in 10.2% (n = 6 of 59), 7.3% (n = 3 of 38), 16.7% (n = 3 of 18), and 66.7% (n = 10 of 15) (P < .001) of patients receiving 5 mg/kg every 8 weeks, 10 mg/kg every 8 weeks, 10 mg/kg every 6 weeks, and 10 mg/kg every 4 weeks, respectively. Dose escalation to 240 mg every other week led to recapture clinical remission in 93.3% (n = 14 of 15). Infliximab serum levels increased after the switch (P < .0001) except for patients receiving 10 mg/kg every 4 weeks. In multivariable analysis, 10 mg/kg every 4 weeks regimen (odds ratio, 12.4; 95% confidence interval, 1.6-98.4; P = .017) and fecal calprotectin >250 μg/g at baseline (odds ratio, 5.4; 95% confidence interval, 1.1-27.6; P = .042) had a higher risk of relapse as well as reduced (41.7%) or stable (36.8%) infliximab serum levels between baseline and visit 1 compared with increased serum levels (12.7%) (P = .020 and P = .019, respectively). Patients' acceptability (10-point scale) was improved by the switch (6.9 ± 1.6 vs 8.6 ± 1.4; P < .0001). No severe adverse event was reported., Conclusions: Switching from intravenous to subcutaneous infliximab 120 mg every other week is safe and well accepted, leading to a low risk of relapse in IBD patients except for those receiving 10 mg/kg every 4 weeks requiring 240 mg every other week., (Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Introduction: The first subcutaneous (SC) formulation of infliximab (IFX), CT‑P13 SC, has been approved in Europe and Australia, including for the treatment of inflammatory bowel disease (IBD)., Areas Covered: We provide a comprehensive overview of available clinical trial and real-world data for IFX SC treatment of IBD, focusing on the potential benefits of switching from IFX intravenous (IV) to IFX SC. We evaluate emerging evidence for IFX SC treatment for difficult-to-treat IBD, use as monotherapy, and suitability for patients receiving escalated IFX IV doses. Therapeutic drug monitoring approaches and patient and healthcare system perspectives on IFX SC are also discussed., Expert Opinion: IFX SC represents a significant treatment innovation in the tumor necrosis factor inhibitor class after approximately 20 years of IFX IV availability. Evidence suggests that IFX SC is well tolerated and is associated with high patient acceptance and satisfaction. In addition, effectiveness is maintained in patients with stable disease following switch from IFX IV. Switching may be advisable, given the clinical benefits of IFX SC and its potential to improve healthcare service capacity. There are several areas requiring further research, including the role of IFX SC in difficult-to-treat and refractory disease, and the feasibility of IFX SC monotherapy.

Introduction: Loss of response to golimumab occurs in nearly 40% of patients with ulcerative colitis (UC). Unlike others anti-TNF, no study has reported a correlation between serum golimumab level and response to drug intensification. The objective of this study was to evaluate the effectiveness and safety of golimumab intensification and to identify the best threshold of serum golimumab before drug intensification predictive of response., Patients and Methods: We included all consecutive patients with active UC with loss of response to golimumab in a prospective multicentric cohort study. Patients with loss of response at 50 mg q4 weeks (W) and 100 mg q4W underwent therapeutic intensification at 100 mg q4W and 100 mg q2W, respectively. Effectiveness and safety were assessed between Weeks 2 and 4 (visit 2) and between Weeks 4 and 8 (visit 3) after intensification. Serum level and anti-golimumab antibodies were evaluated at each medical visit (Lisa Tracker, Theradiag France)., Results: A total of 47 UC patients (Female, 50%; median age, 39 years (IQR, 27-52)) treated with golimumab for a median of 20.4 weeks (IQR, 10.7-38.3) were included. The median partial Mayo score was 6 (IQR, 5-7), and the median endoscopic Mayo score was 3 (IQR, 2-3). The median golimumab serum level before intensification was 2.23 μg/mL (IQR, 1.02-3.96) and only one patient (2.1%) had anti-drug antibodies. At Visit 2 (Week 2-4), 40% patients experienced clinical response, 10% clinical remission, 33% endoscopic response and 23% endoscopic remission. At Visit 3 (Week 4-8), 44% of patients had clinical response, 22% of patients had clinical remission, 45% of patients had endoscopic response, and 41% of patients had endoscopic remission. The median golimumab levels before intensification do not differ between responders and non-responders (2.13 μg/ml (0.76-2.76) and 3.37 μg/ml (IQR, 1.08-4.67), respectively; p = 0.14) assessed at Visit 3. Golimumab intensification to 100 mg q4W (vs q2W) (OR 1.98, 95% CI [1.06-3.70]; p = 0.032) was significantly associated with clinical remission at Visit 3. Serum drug level at baseline or the presence of antidrug antibodies were not associated with clinical or endoscopic remission/response. Two serious adverse events (one infection and one UC flare) were reported during the 24-week follow-up., Conclusion: In this prospective multicentric study, half of patients recaptured response following golimumab intensification in UC. Therapeutic drug monitoring did not predict response after optimisation of golimumab., (© 2023 John Wiley & Sons Ltd.)

Immunotherapy has become the standard of care for several types of cancer, such as melanoma. However, it can induce toxicity, including immune checkpoint inhibitor-induced colitis (CIC). CIC shares several clinical, histological, biological, and therapeutic features with inflammatory bowel disease (IBD). Clostridium difficile infection (CDI) can complicate the evolution of IBD. We aimed to characterize the association between CDI and CIC in patients treated with anti-CTLA-4 and anti-PD-1 for melanoma. Patients from nine centers treated with anti-CTLA-4 and anti-PD-1 for melanoma and presenting with CDI from 2010 to 2021 were included in this retrospective cohort. The primary endpoint was the occurrence of CIC. The secondary endpoints were findings allowing us to characterize CDI. Eighteen patients were included. Eleven were treated with anti-PD-1, four with anti-CTLA-4, and three with anti-PD-1 in combination with anti-CTLA-4. Among the 18 patients, six had isolated CDI and 12 had CIC and CDI. Among these 12 patients, eight had CIC complicated by CDI, three had concurrent CIC and CDI, and one had CDI followed by CIC. CDI was fulminant in three patients. Endoscopic and histological features did not specifically differentiate CDI from CIC. Nine of 11 patients required immunosuppressive therapy when CDI was associated with CIC. In nine cases, immunotherapy was discontinued due to digestive toxicity. CDI can be isolated or can complicate or reveal CIC. CDI in patients treated with immunotherapy shares many characteristics with CDI complicating IBD. Stool tests for Clostridium difficile should be carried out for all patients with diarrhea who are being treated with immunotherapy., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Aims: Paediatric-onset IBD [pIBD] is associated with an increased risk of cancer and mortality in adulthood. The aims of this study were to measure the incidence of cancer and mortality in patients with pIBD and identify factors associated with mortality and cancer., Methods: All patients diagnosed with Crohn's disease [CD] or ulcerative colitis [UC] before the age of 17 years between 1988 and 2011 in the EPIMAD registry were retrospectively followed until 2013 for cancer and 2015 for mortality. Standardized incidence [SIR] and mortality ratios [SMR] were estimated compared to the general population. Cox regression was used to compare the effect of exposures on cancer and mortality among IBD patients., Results: We included 1344 patients [52% males, 75% CD], totalling 12 957 patient-years for cancer incidence and 18 817 patient-years for mortality. There were 14 cases of cancer [median age 27.8 years] and 15 deaths [median age 28.8 years]. The incidence of cancer and of mortality were increased compared to the general population: all-cancer SIR = 2.7 (95% confidence interval [CI]: 1.5-4.8), SMR = 1.7 [95% CI: 1.0-2.8]. Colorectal cancer had the highest SIR and SMR: SIR = 41.2 [95% CI: 17.2-99.0], SMR = 70.4 [95% CI 22.7-218.2]. Cancer was associated with (hazard ratio [HR], 95% CI): active smoking at diagnosis [5.5, 1.8-16.5], p = 0.002; any exposure to anti-tumour necrosis factor [6.1, 1.7-22.3], p = 0.0065; and exposure to combination therapy [7.4, 1.8-29.7], p = 0.0047. Mortality was associated with extraintestinal manifestations (HR 4.9 [95% CI: 1.7-13.8], p = 0.003)., Conclusions: In this large population-based cohort, patients with pIBD had an increased risk of both cancer [2.7-fold] and mortality [1.7-fold], particularly for colorectal cancer., (© 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.)