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Manakins (Pipridae) are well know for elaborate male sexual displays and ornate plumage coloration, both of which are thought to have evolved as a consequence of lekking breeding, the prevalent mating system in the family. Less attention has been paid to a handful of 'drab' manakin species, in which sexual dimorphism appears to be reduced or absent. Using character reconstruction, we show that these 'exceptions to the rule' represent phylogenetically independent cases of losses in sexual dimorphism, and as such could provide a focal group to investigate the link between changes in morphology and in life history (e.g. mating system). We take a first step in this direction by focusing on two subspecies of the putatively monomorphic green manakin Xenopipo holochlora to formally confirm that the species is sexually monomorphic in size and plumage color and test the prediction that sexual monomorphism is associated with the loss of lekking behavior in this species. Our results show that size dimorphism is present but limited in the green manakin, with substantial overlap in male and female morphometric measures, and that sexes are largely monochromatic (including from an avian perspective), despite marked coloration differences between subspecies. Behavioral observations indicate that males do not form leks and do not engage in elaborate sexual displays, that there is no stable pair bond formation, and that females provide parental care alone. These findings are consistent with the idea that changes in mating behavior may have driven changes in morphology in Pipridae, and we encourage similar studies on other drab manakins to better understand this relationship.

Crohn's Disease (CD) can affect any part of the gastrointestinal (GI) tract, including the upper GI tract (UGIT). However, the definitions and classifications of upper GI CD (UGICD) vary. We conducted a scoping review to explore how UGIT and UGICD are defined and to assess the heterogeneity of these definitions in published CD guidelines, aiming to inform future initiatives for harmonizing definitions. We conducted a search of MEDLINE and Embase for English-language guidelines on CD that mentioned upper GI-related terms in the titles, abstracts, or keywords from inception until 26 July 2024. Definitions of UGIT and UGICD were summarized descriptively. Of 1132 citations, only 19 records met our inclusion criteria. Only eight were identified as CD guidelines. None of them focuses on UGICD. Among these, five diagnostic guidelines explicitly mentioned "upper GI" in their abstracts. Only the joint European Crohn's and Colitis Organisation and European Society of Gastrointestinal and Abdominal Radiology guidelines clearly defined the UGIT. Most guidelines mentioned UGI terms related to upper endoscopy or biopsy only. It was unclear whether these guidelines typically included the esophagus, stomach, and duodenum in the definition of UGICD while excluding the distal small intestine. Although the latest guideline related to pediatric-onset IBD cited the 2011 Paris classification, none of the three guidelines published after that explicitly mentioned the proposed subdivided location of the upper disease. There is a lack of consistent reporting in defining UGICD according to disease location. It is unclear whether there is a consensus on excluding the small intestine beyond the duodenum. Additionally, there is no indication that the subdivided location of UGIT was considered in CD guideline development. Greater consistency in definitions would aid in diagnosis, clinical care, epidemiological research and inclusion into clinical trials. These findings underscore the need for developing a framework to standardize the classification of UGICD, especially for clinical trials., (© 2024 The Author(s). United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Background: The performance of bowel preparation (BP) in patients with Crohn's disease (CD) is unknown., Aims: To evaluate the operating properties of instruments used to assess BP quality in patients with CD., Methods: We used the Boston Bowel Preparation Scale, modified Boston Bowel Preparation Scale, Harefield Cleansing Scale, Food and Drug Administration Bowel Cleansing Assessment Scale (BCAS), and a 100-mm visual analogue scale of bowel cleanliness to assess BP quality in 50 videos from 40 patients with CD. We assessed endoscopic activity with the Simple Endoscopic Score for CD (SES-CD). Assessments were on endoscope insertion and withdrawal. Reliability was quantified using the intraclass correlation coefficient (ICC). We assessed validity by within-patient correlation between instruments and the visual analogue scale using mixed-effect models. The correlation between BP quality and SES-SD scores was assessed using Spearman's rho., Results: Inter- and intra-rater reliability for all BP quality instruments was substantial (ICC ≥0.61) except for the Food and Drug Administration BCAS on insertion (inter-rater reliability ICC ≥0.41). The visual analogue scale had substantial inter- and almost perfect (ICC ≥0.81) intra-rater reliability. Correlation coefficients for the validity of the instruments exceeded 0.58. BP quality and endoscopic disease activity scores in the colon were negatively correlated., Conclusion: Most existing instruments reliably assess BP quality in patients with CD. These results support the use of these instruments in clinical practice, provide a framework for scoring BP quality in CD clinical trials, and support evaluation of novel BP agents in patients with CD., (© 2024 The Author(s). Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Background: Stricturing, penetrating complications and extraintestinal manifestations (EIMs) are frequent in patients with inflammatory bowel disease (IBD). There is limited data on the prevalence of these complications in patients with IBD. Therefore, we aimed to assess the burden of these complications detected incidentally on cross-sectional imaging., Methods: A retrospective study conducted at two tertiary care centers in London, Ontario. Patients (≥18 years) with a confirmed diagnosis of IBD who underwent CT enterography (CTE) or MR enterography (MRE) between 1 Jan 2010 and 31 Dec 2018 were included. Categorical variables were reported as proportions and the mean and standard deviations were reported for continuous variables., Results: A total of 615 imaging tests (MRE: 67.3% [414/615]) were performed in 557 IBD patients (CD: 91.4% [509/557], UC: 8.6% [48/557]). 38.2% (213/557) of patients were male, with mean age of 45.6 years (±15.8), and median disease duration of 11.0 years (±12.5). Among patients with CD, 33.2% (169/509) had strictures, with 7.8% having two or more strictures and 66.3% considered inflammatory. A fistula was reported in 10.6% (54/509), the most common being perianal fistula (27.8% [15/54]), followed by enterocutaneous fistula (16.8% [9/54]), and enteroenteric fistula (16.8% [9/54]). Additionally, 7.4% (41/557) of patients with IBD were found to have an EIM on cross-sectional imaging, with the most prevalent EIM being cholelithiasis (63.4% [26/41]), followed by sacroiliitis (24.4% [10/41]), primary sclerosing cholangitis (4.8% [2/41]) and nephrolithiasis (4.8% [2/41])., Conclusions: Approximately 40% of patients with CD undergoing cross-sectional imaging had evidence of a stricture or fistulizing disease, with 7% of patients with IBD having a detectable EIM. These results highlight the burden of disease and the need for specific therapies for these disease phenotypes., (© 2024 The Author(s). United European Gastroenterology Journal published by Wiley Periodicals LLC. on behalf of United European Gastroenterology.)

Background: Crohn's disease (CD) is characterized by discontinuous inflammation. Failure to identify skipping lesions of the terminal ileum (TI) or transmural changes can lead to incorrect management., Methods: Eligible adult patients with CD undergoing ileo-colonoscopy and computed tomography enterography or magnetic resonance enterography within 6 months. We determined the prevalence of endoscopic skipping (normal ileum on colonoscopy but proximal small bowel inflammation on cross-sectional imaging), skip lesions (discontinuous inflammation along the gastrointestinal tract identified on cross-sectional imaging), structuring, and penetrating complications., Results: Among 202 patients, 45 (22.3%) had endoscopic skipping proximal to TI intubation. Fifty patients (24.5%) had small bowel skip lesions, primarily in the ileum. Strictures were identified in 34 patients (16.8%) through both imaging and ileo-colonoscopy, in 21 patients (10.4%) solely through cross-sectional imaging, and in 3 patients (1.5%) solely through ileo-colonoscopy. Approximately 36.2% of stricturing cases would be missed without cross-sectional imaging. Penetrating complications, including abscesses (2.5%) and various fistula types (4.9%), were detected in 15 (7.4%) patients., Conclusions: Ileo-colonoscopy missed detection of active CD in approximately one-fifth of cases due to more proximal disease location. Stricturing disease might be missed in more than a third of cases if cross-sectional imaging is not performed., (© 2024 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

Introduction: Symptoms, endoscopy and histology have been proposed as therapeutic targets in ulcerative colitis (UC). Observational studies suggest that the achievement of histologic remission may be associated with a lower risk of complications, compared with the achievement of endoscopic remission alone. The actiVE ulcerative colitis, a RanDomIsed Controlled Trial (VERDICT) aims to determine the optimal treatment target in patients with UC., Methods and Analysis: In this multicentre, prospective randomised study, 660 patients with moderate to severe UC (Mayo rectal bleeding subscore [RBS] ≥1; Mayo endoscopic score [MES] ≥2) are randomly assigned to three treatment targets: corticosteroid-free symptomatic remission (Mayo RBS=0) (group 1); corticosteroid-free endoscopic remission (MES ≤1) and symptomatic remission (group 2); or corticosteroid-free histologic remission (Geboes score <2B.0), endoscopic remission and symptomatic remission (group 3). Treatment is escalated using vedolizumab according to a treatment algorithm that is dependent on the patient's baseline UC therapy until the target is achieved at weeks 16, 32 or 48. The primary outcome, the time from target achievement to a UC-related complication, will be compared between groups 1 and 3 using a Cox proportional hazards model., Ethics and Dissemination: The study was approved by ethics committees at the country level or at individual sites as per individual country requirements. A full list of ethics committees is available on request. Study results will be disseminated in peer-reviewed journals and at scientific meetings., Trial Registration Number: EudraCT: 2019-002485-12; NCT04259138., Competing Interests: Competing interests: VJ has received consulting/advisory board fees from AbbVie, Alimentiv Inc (formerly Robarts Clinical Trials), Arena Pharmaceuticals, Asieris, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Fresenius Kabi, Galapagos, GlaxoSmithKline, Genentech, Gilead, Janssen, Merck, Mylan, Pandion, Pendopharm, Pfizer, Reistone Biopharma, Roche, Sandoz, Takeda and Topivert; and speaker’s fees from Abbvie, Ferring, Janssen, Pfizer, Shire and Takeda. GZ has received consulting fees from Alimentiv Inc. ZW is an employee of Alimentiv Inc. SA is an employee of Takeda Pharmaceuticals. JFC reports receiving research grants from AbbVie, Janssen Pharmaceuticals and Takeda; payment for lectures from AbbVie, Amgen, Allergan. Ferring Pharmaceuticals, Shire and Takeda; consulting fees from AbbVie, Amgen, Arena Pharmaceuticals, Boehringer Ingelheim, BMS, Celgene Corporation, Eli Lilly, Ferring Pharmaceuticals, Galmed Research, Genentech, Glaxo Smith Kline, Janssen Pharmaceuticals, Kaleido Biosciences, Imedex, Immunic, Iterative Scopes, Merck, Microbia, Novartis, PBM Capital, Pfizer, Protagonist Therapeutics, Sanofi, Takeda, TiGenix, Vifor; and holds stock options in Intestinal Biotech Development. GRD has served as a consultant and/or received speaker fees from Abbvie, Alimentiv, AstraZeneca, Biora (Progenity), Boehringer Ingelheim, Bristol Myers Squibb, Celltrion Healthcare, Cytoki Pharma, Eli Lilly, Ferring, Galapagos, GlaxoSmithKline, Gossamer Bio, Immunic, InDex Pharmaceuticals, Janssen, Johnson & Johnson, Kaleido, Pfizer, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Takeda, Tillotts and Ventyx Biosciences. MF is an employee of Takeda Pharmaceuticals. GWM is a consultant for Alimentiv and in receipt of research funding from AstraZeneca and Johnson and Johnson. LPB has received personal 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. WJS reports receiving consulting fees from Abbvie, Abivax, Alfasigma, Alimentiv, Beigene, Biora (Progenity), Celltrion, Forbion, Genentech, Gossamer Biosciences, Index Pharmaceuticals, Prometheus Biosciences, Protagonist Therapeutics, Shoreline Biosciences, Vedanta Biosciences, Ventyx Biosciences, Zealand Pharma; and stock or stock options from BeiGene, Gossamer Bio, Biora (Progenity), Prometheus Biosciences, Prometheus Laboratories, Shoreline Biosciences, Ventyx Biosciences, Vimalan Biosciences, Vivreon Gastrosciences; he is an employee at Shoreline Biosciences and Ventyx Biosciences. Spouse: Iveric Bio—consultant, stock options; Biora (Progenity)—stock; Prometheus Biosciences—employee, stock, stock options; Prometheus Laboratories—stock, stock options; Ventyx Biosciences—stock, stock options; Vimalan Biosciences—stock, stock options. SS reports research grants from Takeda, Pfizer, Tillotts Pharma, Abbvie and Biogen; and personal fees for speaker role and advisory board meetings from Janssen, Amgen, Tillotts Pharma, Abbvie, Takeda, Celgene, Roche, Pharmacosmos, and Falk Pharma outside the submitted work. ST has received grants/research support from AbbVie, Buhlmann, Celgene, ECCO, Helmsley Trust, IOIBD, Janssen, Lilly, Pfizer, Takeda, UCB, UKIERI, Vifor and Norman Collisson Foundation; consulting fees from Abacus, AbbVie, Actial, ai4gi, Alcimed, Allergan, Amgen, Apexian, Aptel, Arena, Asahi, Aspen, Astellas, Atlantic, AstraZeneca, Barco, Biocare, Biogen, BLPharma, Boehringer Ingelheim, BMS, Buhlmann, Calcico, Celgene, Cellerix, Cerimon, ChemoCentryx, Chiesi, CisBio, ComCast, Coronado, Cosmo, Ducentis, Dynavax, Elan, Enterome, EQrX, Equillium, Falk, Ferring, FPRT Bio, Galapagos, Genentech/Roche, Genzyme, Gilead, Glenmark, Grunenthal, GSK, GW Pharmaceuticals, Immunocore, Immunometabolism, Indigo, Janssen, Lexicon, Lilly, Medarex, Medtrix, Merck, Merrimack, Mestag, Millenium, Neovacs, Novartis, Novo Nordisk, NPS-Nycomed, Ocera, Optima, Origin, Otsuka, Palau, Pentax, Pfizer, Pharmaventure, Phesi, Phillips, P&G, Pronota, Protagonist, Proximagen, Resolute, Robarts, Sandoz, Sanofi, Santarus, Satisfai, Sensyne Health, Shire, SigmoidPharma, Sorriso, Souffinez, Syndermix, Synthon, Takeda, Theravance, Tigenix, Tillotts, Topivert, Trino Therapeutics with Wellcome Trust, TxCell, UCB Pharma, Vertex, VHsquared, Vifor, Warner Chilcott and Zeria; speaker fees from AbbVie, Amgen, Biogen, BMS, Falk, Ferring, Janssen, Lilly, Pfizer, Shire, Takeda and UCB. He has no stocks or share options. SV has received grants from AbbVie, J&J, Pfizer, Takeda and Galapagos; consulting and/or speaking fees from AbbVie, AbolerIS Pharma, AgomAb, Alimentiv, Arena Pharmaceuticals, AstraZeneca, Avaxia, BMS, Boehringer Ingelheim, Celgene, CVasThera, Cytoki Pharma, Dr Falk Pharma, Ferring, Galapagos, Genentech-Roche, Gilead, GSK, Hospira, Imidomics, Janssen, J&J, Lilly, Materia Prima, MiroBio, Morphic, MrMHealth, Mundipharma, MSD, Pentax, Pfizer, Prodigest, Progenity, Prometheus, Robarts Clinical Trials, Second Genome, Shire, Surrozen, Takeda, Theravance, Tillots Pharma AG and Zealand Pharma. GR is an employee of Alimentiv Inc. JS is an employee of Alimentiv Inc. JH has received consulting fees from Alimentiv Inc.; and speaker’s fees from Abbvie, Janssen and Takeda. CM has received consulting fees from AbbVie, Alimentiv, Amgen, AVIR Pharma, Bristol Myers Squibb, Ferring, Fresenius Kabi, Janssen, McKesson, Mylan, Takeda, Pfizer and Roche; speaker's fees from AbbVie, Amgen, AVIR Pharma, Alimentiv, Ferring, Janssen, Takeda and Pfizer; and research support from Pfizer. RS is an employee of Alimentiv Inc. SCM is an employee of Alimentiv Inc. NA reports no conflicts of interest. MB has received honoraria from Shire, Allergan, Pfizer, and Takeda; advisory board fees from AbbVie, Takeda, Janssen, Lupin, Gilead, Pfizer, and Novo Nordisk; clinical trials: AbbVie, Novo Nordisk, Gilead, Takeda, Boehringer Ingelheim, Janssen, Pfizer, AstraZeneca and Intercept; research publications: AbbVie (2021–letter signed). PB reports receiving research grants from Abbvie, Amgen, Celltrion, Mylan, Pfizer and Takeda; lecture fees from AbbVie, Celltrion, Janssen, Lilly, and Takeda; and consulting fees Abbvie, Arena Pharmaceuticals, BMS, Celltrion, Dr Falk, Galapagos, Janssen, Lilly, Pentax, PSI-CRO, Roche, Takeda, and Tetrameros. DG has received advisory board fees from Takeda, Abbvie, Janssen, Pfizer, Merck, and Freseni Kabi. WH reports no conflicts of interest. MH reports no conflicts of interest. MK has received personal fees from Shire, a Takeda company, during the conduct of the study; personal fees and non-financial support from Takeda; personal fees and non-financial support from Janssen; personal fees and non-financial support from Ferring, outside the submitted work. RP has received consulting/advisory board fees from AbbVie, Janssen, Pfizer and Allergan. MSS has received consulting, speaker and advisory board fees from Abbvie, Janssen, Pfizer, and Takeda. LW reports no conflicts of interest. BGF is a scientific advisory board member for AbbVie, Allergan, Amgen, AstraZeneca, Avaxia Biologics, Boehringer-Ingelheim, Bristol-Myers Squibb, Celgene, Elan, Biogen, Ferring, Genentech–Roche, Janssen–Johnson & Johnson, Merck, Millennium, Nestlé, Novo Nordisk, Novartis, Pfizer, Prometheus, Protagonist, Receptos, Salix, Sigmoid Pharma, Takeda, Teva, TiGenix, Tillotts Pharma and UCB Pharma; consulting fees from AbbVie, Actogenix, Akros, Albireo Pharma, Allergan, Amgen, AstraZeneca, Avaxia Biologics, Avir Pharma, Axcan, Baxter Healthcare, Biogen Idec, Boehringer Ingelheim, Bristol-Myers Squibb, Calypso Biotech, Celgene, Elan–Biogen, EnGene, Ferring, Genentech–Roche, GiCare Pharma, Gilead Sciences, Given Imaging, GlaxoSmithKline, Ironwood, Janssen Biotech–Centocor, Janssen–Johnson & Johnson, Kyowa Hakko Kirin, Eli Lilly, Merck, Mesoblast Pharma, Millennium, Nestlé, Novo Nordisk, Novartis, Pfizer, Prometheus, Protagonist, Receptos Salix, Sanofi, Shire, Sigmoid Pharma, Synergy Pharma, Takeda, Teva, TiGenix, Tillotts Pharma, UCB Pharma, Vertex, VHsquared, Wyeth, Zealand and Zygenia; lecture fees from AbbVie, Janssen–Johnson & Johnson, Takeda, and UCB Pharma, and grant support from AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Janssen Biotech–Centocor, Janssen–Johnson & Johnson, Pfizer, Receptos, Sanofi, and Takeda and is the Senior Scientific Officer of Alimentiv Inc. Alimentiv Inc is an academic gastrointestinal contract research organisation (CRO), operating under the Alimentiv Health Trust. Alimentiv Inc. provides comprehensive clinical trial services, precision medicine offerings, and centralised imaging solutions for endoscopy, histopathology and other imaging modalities. The beneficiaries of the Alimentiv Health Trust are the employees of the enterprises it holds. BGF, GRD, GZ, VJ and WJS are consultants to Alimentiv Inc. and have a primary academic appointment; they do not hold equity positions or shares in Alimentiv Inc., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Aims: We conducted a systematic review to assess medical therapy for the treatment and prevention of pouchitis., Methods: Randomised controlled trials (RCTs) of medical therapy in adults with or without pouchitis were searched to March 2022. Primary outcomes included clinical remission/response, maintenance of remission and prevention of pouchitis., Results: Twenty RCTs (N = 830) were included. Acute pouchitis: One study compared ciprofloxacin with metronidazole. At 2 weeks, 100% (7/7) of ciprofloxacin participants achieved remission, compared with 67% (6/9) of metronidazole participants (RR: 1.44, 95% CI: 0.88-2.35, very low certainty evidence). One study compared budesonide enemas with oral metronidazole. Fifty percent (6/12) of budesonide participants achieved remission compared with 43% (6/14) of metronidazole participants (RR: 1.17, 95% CI: 0.51-2.67, low certainty evidence). Chronic pouchitis: Two studies (n = 76) assessed De Simone Formulation. Eighty-five percent (34/40) of De Simone Formulation participants maintained remission at 9-12 months compared with 3% (1/36) placebo participants (RR: 18.50, 95% CI: 3.86-88.56, moderate certainty evidence). One study assessed vedolizumab. Thirty-one percent (16/51) of vedolizumab participants achieved clinical remission at 14 weeks compared with 10% (5/51) of placebo participants (RR: 3.20, 95% CI: 1.27-8.08, moderate certainty evidence)., Prophylaxis: Two studies assessed De Simone Formulation. Ninety percent (18/20) of De Simone Formulation participants did not develop pouchitis compared with 60% (12/20) of placebo participants (RR: 1.50, 95% CI: 1.02-2.21, moderate certainty evidence)., Conclusions: Apart from vedolizumab and the De Simone formulation, the effects of other medical interventions for pouchitis are uncertain., (© 2023 John Wiley & Sons Ltd.)

Introduction: With the expanding therapeutic armamentarium for inflammatory bowel disease (IBD), real-world data may help inform drug positioning. We assessed clinical, endoscopic, imaging, and biochemical response/remission outcomes in patients with Crohn's disease (CD) treated with ustekinumab in a large Canadian IBD center., Methods: A retrospective cohort study of CD patients was treated with ustekinumab. Clinical, endoscopic, radiological, and biochemical response and remission outcomes were stratified by prior biologic exposure status. Hazard ratios for biologic exposure status were estimated using Cox proportional hazard models and subgroup-specific incidence rates for healing., Results: A total of 231 patients (55.9% female, median 45.8 years) were identified as receiving ustekinumab during the study period, with 2 patients subsequently excluded (N = 229). Of these patients, 79.0% (181 of 229) were bio-experienced, with 38.7% (70 of 181) having failed 1 biologic and 61.3% (111 of 181) having failed ≥2 biologics. At 3 months of follow-up after induction, clinical remission (Harvey-Bradshaw Index ≤4) was achieved by 59.1% (62 of 105) of bio-experienced patients and 79.4% (27 of 34) of bio-naïve patients (relative risk [RR], 1.34; 95% CI, 1.06-1.70; P = .013). Endoscopic remission (absence of mucosal ulcers) was achieved in 37.9% (33 of 87) cases. Rate of endoscopic healing (either endoscopic response or remission) per 1000 person-months was 72.7 (95% CI, 42.4-125.1) and 50.2 (37.9-66.4); and the median time to endoscopic response was 8.4 months (95% CI, 6.4-9.8) and 15.4 months (95% CI, 10.3-17.9) in bio-naïve vs bio-experienced patients, respectively. Imaging response/remission and steroid-free remission rates were higher in bio-naïve patients., Conclusion: In this large real-world cohort of CD patients with complex phenotypes and high rates of prior biologic exposure, we observed that ustekinumab was effective and safe with higher rates of improvement in bio-naïve subjects across a range of end points., (© The Author(s) 2022. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Despite regular need for colonoscopy in patients with Crohn's disease (CD), the efficacy and tolerability of bowel preparation (BP) agents is rarely assessed in this population. Assessing BP quality with existing scales may be challenging in CD due to presence of inflammation, bowel resection, and strictures., Aims: To provide recommendations for assessing BP quality in clinical trials for CD using a modified Research and Development/University of California, Los Angeles appropriateness process., Methods: Based on systematic reviews and a literature search, 110 statements relating to BP quality assessment in CD were developed. A panel of 15 gastroenterologists rated the statements as appropriate, uncertain, or inappropriate using a 9-point Likert scale., Results: Panelists considered it appropriate that central readers, either alone or with local assessment, score BP quality in clinical trials. Central readers should be trained on scoring BP quality and local endoscopists on performing high-quality video recording. Both endoscope insertion and withdrawal phases should be reviewed to score BP quality in each colonic segment and segments should align with endoscopic disease activity indices. The Harefield Cleansing Scale and the Boston Bowel Preparation Scale were considered appropriate. The final score should be calculated as the average of all visualized segments. Both total and worst segment scores should also be assessed., Conclusions: We developed a framework for assessing BP quality in patients with CD based on expert feedback. This framework could support the development or refinement of BP quality scales and the integration of BP quality assessment in future CD studies., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: We aimed to evaluate the real-world effectiveness and safety of tofacitinib for the treatment of ulcerative colitis (UC)., Methods: REMIT-UC is a Canadian multicenter cohort study. Standardized data collection was performed on 334 consecutive adult outpatients with UC treated with tofacitinib. The primary outcomes were achievement of clinical and endoscopic remission. Safety outcomes were reported using incidence rates (events/100 patient-years of exposure). A multivariable Cox proportional hazards model was used to evaluate predictors of loss of response after tofacitinib dose de-escalation to 5 mg twice daily (BID)., Results: Clinical remission was achieved by 35.3% (106/300), 36.0% (104/289), and 35.2% (93/264) of patients at weeks 12, 24, and 52, respectively. Endoscopic remission was achieved by 18.5% (15/81), 23.0% (28/122), and 25.7% (35/136) of patients at weeks 12, 24, and 52, respectively. Incidence of serious infections, herpes zoster, and venous thromboembolism were 2.1 [0.9-4.2], 0.5 [0.1-1.9], and 1.1 [0.3-2.7], respectively. Among responders, 44.5% (109/245) lost response during follow-up, which was recaptured in 54.9% (39/71) of patients who re-escalated to 10 mg BID. Patients with a baseline Mayo endoscopic score of 3 (adjusted hazard ratio 3.60 [95% confidence interval: 1.70-7.62]) and prior biologic failure (adjusted hazard ratio 3.89 [95% confidence interval: 1.28-11.86]) were at a higher risk for losing response after dose reduction., Discussion: One-third of patients with UC treated with tofacitinib achieved clinical remission with few serious adverse events. However, half of patients lost response with de-escalation, which was only partially recaptured with increasing the maintenance dose. Those with negative prognostic factors should be counselled about the risks and benefits of continuing high doses of tofacitinib., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background and Aims: Perianal fistulizing disease is a common complication of Crohn's disease [CD], for which new therapies are urgently needed. To assist the design of clinical trials for novel therapeutics, we conducted a systematic review and meta-analysis of randomised controlled trials [RCTs] to quantify placebo rates and identify factors influencing them in perianal CD [pCD]., Methods: We searched MEDLINE, Embase and CENTRAL from inception to June 2021. Eligible studies were placebo-controlled trials of pharmacological interventions for pCD. Placebo fistula response and remission rates for induction and maintenance trials were extracted and pooled using a random-effects model. Mixed-effects meta-regression was used to evaluate the impact of patient and study-level characteristics on point estimates., Results: In 17 RCTs [13 induction, five maintenance] the pooled placebo fistula response and remission rate for induction trials was 25% (95% confidence interval [CI] 17-36%) and 17% [95% CI 11-25%], respectively. For maintenance trials, the pooled placebo fistula response and remission rate was 23% [95% CI 17-32%] and 19% [95% CI 14-25%], respectively. Trials enrolling patients with less disease activity and a higher proportion with ileal predominant disease were associated with significantly higher placebo response rates. Trials originating in Europe [compared to North America], therapies requiring perianal injection and a longer timepoint to measure remission were associated with higher placebo remission rates., Conclusions: Placebo response and remission rates in pCD trials are influenced by patient and disease-related factors, as well as the type of intervention being studied. These contemporary rates will inform trial design for novel therapeutics., (© 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.)

Background and Aims: Treatment options for proctitis are limited. To assist trial design for novel therapeutics, we conducted a systematic review and meta-analysis of proctitis randomized controlled trials [RCTs] to quantify placebo rates and identify factors influencing them., Methods: We searched MEDLINE, EMBASE and CENTRAL from inception to June 2021. Placebo-controlled trials of pharmacological interventions for proctitis were eligible. Placebo clinical response and remission rates for induction and maintenance trials were extracted and pooled using a random-effects model. Mixed-effects meta-regression was used to evaluate the impact of patient and study-level characteristics., Results: Twenty RCTs [17 induction and four maintenance phases] were included. The most common intervention was aminosalicylates and most studies investigated topical medications. The pooled placebo clinical response and remission rates for induction trials were 28% (95% confidence interval [CI] 22-35%; n = 17) and 20% [95% CI 12-32%; n = 9], respectively. Pooled placebo endoscopic response and remission rates were 32% [95% CI 26-39%, n = 12] and 18% [95% CI 9-33%, n = 6], respectively. For maintenance trials, the pooled placebo clinical remission rate was 29% [95% CI 16-46%, n = 17]. Trials published after 2005 and trials with a longer duration of follow-up were associated with significantly lower placebo response rates. Nineteen of 20 studies were assessed as having an unclear risk of bias, reflecting the historical nature of trials., Conclusions: Placebo response and remission rates in proctitis trials are influenced by trial phase and the endpoint being assessed. These contemporary rates will inform trial design for novel therapeutics for treatment of proctitis, which is a large unmet need., (© 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.)

Cancer cells can block the activation of T lymphocytes by deploying inhibitory signals to cell surface receptors that downregulate the immune response. Immune checkpoint inhibitors (ICI) are monoclonal antibodies that regulate the immune response by acting on these receptors. The use of ICI has been successful for cancer types that do not respond well to conventional chemotherapy, showing clinical benefit in various advanced and metastatic cancers and supporting the promise of cancer immunotherapy. However, in some cases, these treatments are associated with immune-related adverse events, many of which affect the digestive system. The treatment of immune-related adverse events depends on the affected organ and the severity of symptoms. Here, we review the commonly used US FDA-approved ICI and briefly outline their mechanism of action. We also describe the resulting collateral effects on the gastrointestinal tract, liver, and pancreas and discuss their management and prognosis., (Copyright © 2022 by The American College of Gastroenterology.)

Background: Treatment options for acute severe ulcerative colitis (ASUC) are limited. Tofacitinib, an approved treatment for moderate to severe ulcerative colitis, could be a potential rescue therapy for ASUC given its rapid onset of action., Objective: To evaluate the effectiveness of tofacitinib in hospitalized patients with ASUC refractory to standard therapy in a real-world setting., Methods: Retrospective observational study of hospitalized adult patients with ASUC treated with tofacitinib between January 2019 and September 2020 at five Canadian centers. We extracted patient demographics, clinical status, biomarkers (C-reactive protein and fecal calprotectin), endoscopic findings, and colectomy-free rate at admission, 30 days, 90 days, and 6 months after tofacitinib initiation., Results: Eight patients with symptoms refractory to standard rescue therapy (corticosteroids ± infliximab if infliximab-naïve prior to admission) were treated with tofacitinib. During index hospitalization, clinical response was observed in 5/8 patients. The median time to discharge post-tofacitinib initiation was 5 days (IQR 5.0-6). At 30 and 90 days, all five responders were in clinical remission. At 6 months, only 3/5 responders remained in clinical remission. The colectomy-free rate was 37.5% during the follow-up period (two colectomies occurred within 30 days; one occurred within 90 days). No drug-related adverse reaction occurred., Conclusion: In this small case-series, tofacitinib was an effective rescue therapy in patients with refractory ASUC. These findings need to be evaluated in a randomized controlled trial., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Precision in estimating placebo rates is important for clinical trial design., Aim: To quantify placebo rates across relevant endpoints in Crohn's disease [CD] trials and identify the factors influencing these rates in a contemporary meta-analysis., Methods: We searched MEDLINE, EMBASE, and CENTRAL from inception to March 2021. Eligible studies were placebo-controlled trials of pharmacological interventions for CD. Placebo response and remission rates for induction and maintenance trials were extracted and pooled by random-effects to quantify placebo rates across studies. Mixed-effects meta-regression was used to evaluate the effects of study-level characteristics on placebo rates., Results: In 125 studies [91 induction, 46 maintenance], placebo clinical remission and response rates for induction studies were 18% (95% confidence interval [CI] 16, 21%], and 32% [95% CI 29, 35%], respectively, and for maintenance studies were 28% [95% CI 23, 34%] and 30% [95% CI 24, 37%], respectively. Endoscopic remission and response rates in induction studies were 8% [95% CI 4, 18%] and 16% [95% CI 11, 23%], respectively. Trials enrolling patients with prior biologic exposure, longer disease duration, and higher CD activity index scores were associated with lower placebo clinical remission rates. Increased duration of follow-up, more follow-up visits, and a greater proportion of patients with colonic disease distribution were associated with higher clinical placebo rates., Conclusions: Placebo remission and response rates in CD trials vary according to the phase of the trial, endpoint assessed, and induction or maintenance design. These contemporary estimates will help to inform future CD trial design., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Several indices exist to measure pouchitis disease activity; however, none are fully validated. As an initial step toward creating a validated instrument, we identified pouchitis disease activity indices, examined their operating properties, and assessed their value as outcome measures in clinical trials., Methods: Electronic databases were searched to identify randomized controlled trials including indices that evaluated clinical, endoscopic, or histologic pouchitis disease activity. A second search identified studies that assessed the operating properties of pouchitis indices., Results: Eighteen randomized controlled trials utilizing 4 composite pouchitis disease activity indices were identified. The Pouchitis Disease Activity Index (PDAI) was most commonly used (12 of 18; 66.7%) to define both trial eligibility (8 of 12; 66.7%), and outcome measures (12 of 12; 100%). In a separate search, 21 studies evaluated the operating properties of 3 pouchitis indices; 90.5% (19 of 21) evaluated validity, of which 42.1% (8 of 19) evaluated the construct validity of the PDAI. Criterion validity (73.7%; 14 of 19) was evaluated through correlation of the PDAI with fecal calprotectin (FCP; r = 0.188 to 0.71), fecal lactoferrin (r = 0.570 to 0.582), and C-reactive protein (CRP; r = 0.584). Two studies assessed correlation of the modified PDAI (mPDAI) with FCP (r = 0.476 and r = 0.565, respectively). Fair to moderate inter-rater reliability of the PDAI (k = 0.440) and mPDAI (k = 0.389) was reported in a single study. Responsiveness of the PDAI pre-antibiotic and postantibiotic treatment was partially evaluated in a single study of 12 patients., Conclusions: Development and validation of a specific pouchitis disease activity index is needed given that existing instruments are not valid, reliable, or responsive., (© 2021 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Aims: We aimed to quantify the magnitude of the association between endoscopic recurrence and clinical recurrence [symptom relapse] in patients with postoperative Crohn's disease., Methods: Databases were searched to October 2, 2020, for randomised controlled trials [RCTs] and cohort studies of adult patients with Crohn's disease with ileocolonic resection and anastomosis. Summary effect estimates for the association between clinical recurrence and endoscopic recurrence were quantified by risk ratios [RR] and 95% confidence intervals [95% CI]. Mixed-effects meta-regression evaluated the role of confounders. Spearman correlation coefficients were calculated to assess the relationship between these outcomes as endpoints in RCTs. An exploratory mixed-effects meta-regression model with the logit of the rate of clinical recurrence as the outcome and the rate of endoscopic recurrence as a predictor was also evaluated., Results: In all, 37 studies [N = 4053] were included. For eight RCTs with available data, the RR for clinical recurrence for patients who experienced endoscopic recurrence was 10.77 [95% CI 4.08 to 28.40; GRADE moderate certainty evidence]; the corresponding estimate from 11 cohort studies was 21.33 [95% CI 9.55 to 47.66; GRADE low certainty evidence]. A single cohort study showed a linear relationship between Rutgeerts score and clinical recurrence risk. There was a strong correlation between endoscopic recurrence and clinical recurrence treatment effect estimates as trial outcomes [weighted Spearman correlation coefficient 0.51]., Conclusions: The associations between endoscopic recurrence and subsequent clinical recurrence lend support to the choice of endoscopic recurrence to monitor postoperative disease activity and as a primary endpoint in clinical trials of postoperative Crohn's disease., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Aims: Quantifying placebo rates and the factors influencing them are essential to inform trial design. We provide a contemporary summary of clinical, endoscopic, histological and safety placebo rates in induction and maintenance clinical trials of ulcerative colitis, and identify factors influencing them., Methods: MEDLINE, EMBASE and the Cochrane library were searched from April 2014 to April 2020, updating a prior meta-analysis that searched from inception to April 2014. We included placebo-controlled trials of aminosalicylates, corticosteroids, immunosuppressives, small-molecules and biologics in adults with ulcerative colitis. Placebo rates were pooled using random-effects and mixed-effects meta-regression models to assess the associated study-level., Results: In 119 trials [92 induction, 27 maintenance] clinical, endoscopic and histological remission placebo rates for induction trials were 11% (95% confidence interval [CI] 9-13%), 19% [95% CI 15-23%] and 15% [95% CI 11-19%], respectively; for maintenance trials, clinical and endoscopic placebo remission rates were 18% [95% CI 12-25%] and 20% [95% CI 15-25%], respectively. Higher endoscopic subscore and a higher rate of exposure to prior biologic therapy at enrolment were associated with lower clinical and endoscopic placebo remission rates. Absence of central reading was associated with an increase in placebo endoscopic response and remission rates. More follow-up visits and increasing trial duration were associated with higher clinical placebo rates., Conclusions: Placebo rates in ulcerative colitis trials vary according to the endpoint assessed, whether it is for assessment of response or remission, and whether the trial is designed for induction or maintenance. These contemporary rates across different endpoints and drug classes will help to inform trial design., (© The Author(s) 2021. 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.)

Pouchitis, Crohn's disease of the pouch, cuffitis, polyps, and extraintestinal manifestations of inflammatory bowel disease are common inflammatory disorders of the ileal pouch. Acute pouchitis is treated with oral antibiotics and chronic pouchitis often requires anti-inflammatory therapy, including the use of biologics. Aetiological factors for secondary pouchitis should be evaluated and managed accordingly. Crohn's disease of the pouch is usually treated with biologics and its stricturing and fistulising complications can be treated with endoscopy or surgery. The underlying cause of cuffitis determines treatment strategies. Endoscopic polypectomy is recommended for large, symptomatic inflammatory polyps and polyps in the cuff. The management principles of extraintestinal manifestations of inflammatory bowel disease in patients with pouches are similar to those in patients without pouches., Competing Interests: Declaration of interests BA reports a research grant from Takeda and personal fees from Janssen, AbbVie, Pfizer, Samsung Biospis, Ferring, Bristol Myers Squibb. CNB reports grants and personal fees from AbbVie, Janssen, Pfizer, and Takeda, personal fees from Amgen, Bristol Myers Squibb, Roche, Sandoz, and Mylan Pharmaceuticals, and speaker fees from Medtronics. DHB reports grants from Medtronic and Takeda. RKC reports personal fees from AbbVie, Janssen, Samsung Bioepis, and Birstol Myers Squibb. FAF reports serving as an advisory board member for Bristol Myers Squibb, Braintree Labs, Gilead, GSK, Iterative Scopes, Janssen, Pfizer, and Sebela; owns stocks and shares in Innovation Pharmaceuticals; and is a member of Data Safety and Monitoring Boards for Lilly and Theravance. SVK reports grants from Gilead Sciences and TechLab. PGK reports personal fees from AbbVie, Janssen, Pfizer, Takeda, and Ferring, and grants from Pfizer and Takeda. JTM reports personal fees from Intuitive Surgical. UN reports grants and personal fees from Takeda, Janssen, and AbbVie, and personal fees from Pfizer. SE-H reports personal fees from AbbVie, Janssen, Takeda, UCB–Ferring, Pfizer, Bristol Myers Squibb, and Prometheus. JPh reports speaker fees from AbbVie. DTR reports personal fees from AbbVie, Abgenomics, Allergan, Arena Pharmaceuticals, Bellatrix Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb, CDx Diagnostics, Celgene/Syneos, Check-Cap, Dizal Pharmaceuticals, Galen Pharma/Atlantica, Genentech/Roche, Ichnos Sciences SA, InDex Pharmaceuticals, Iterative Scopes, Janssen, Lilly, Materia Prima, Marrow River Mgmt, Pfizer, Prometheus Laboratories, Reistone, Takeda, and TechLab. WJS reports grants, personal fees, and stock options from Prometheus Biosciences; grants and personal fees from AbbVie, Abivax, Alimentiv, Arena Pharmaceuticals, Boehringer-Ingelheim, Celgene, Genentech (Roche), Gilead Sciences, GlaxoSmithKline, Janssen, Lilly, Pfizer, Prometheus Biosciences, Seres Therapeutics, Shire, Surrozen, Takeda, and Theravance Biopharma; personal fees and stock options from Beigene, Gossamer Bio, Shoreline Bioscience, and personal fees from Allergan, AbbVie, Amgen, Applied Molecular Transport, Avexegen Therapeutics, Bausch Health, Beigene, Bellatrix Pharmaceuticals, Boston Pharmaceuticals, Bristol Myers Squibb, Celltrion, Cellularity, Conatus, Cosmo Pharmaceuticals, Escalier Biosciences, Ferring, Forbion, Equillium, Gilead, Glanmark Pharmaceuticals, Immunic, Incyte, Index Pharmaceuticals, Intact Therapeutics, Janssen, Kyowa Kirin Pharmaceutical Research, Kyverna Therapeutics, Landos Biopharma, Miraca Life Sciences, Nivalis Therapeutics, Novartis, Nutrition Science Partners, Oppilan Pharma, Pfizer, Progenity, Protagonist Therapeutics, Provention Bio, Reistone Biopharma, Ritter Pharmaceuticals, Shanghai Pharma Biotherapeutics, Sienna Biopharmaceuticals, Sigmoid Biotechnologies, Sterna Biologicals, Sublimity Therapeutics, Takeda, Thetis Pharmaceuticals, Tract, and UCB. ES reports grants and personal fees from AbbVie, Janssen, and Takeda, grants from AstraZeneca, Pfizer, and Genentech, and personal fees from Seres Health, Protagonist Therapeutics, Celgene, Entera Health, Bristol Myers Squibb, and Evidera. JSe reports speaker fees from Janssen and Takeda. DAS reports personal fees from AbbVie, Takeda, UCB, Jansen, Gilead, Pfizer, and Tract. SV reports consultancy fees and/or speaking fees from AbbVie, Arena Pharmaceuticals, Avaxia, Boehringer Ingelheim, Celgene, Dr Falk Pharma, Ferring, Galapagos, Genentech-Roche, Gilead, Hospira, Janssen, Mundipharma, Merck Sharpe & Dohme, Pfizer, Prodigest, Progenity, Prometheus, Robarts Clinical Trials, Second Genome, Shire, Takeda, Theravance, and Tillots Pharma AG, and grants from AbbVie, Johnson & Johnson, Pfizer, and Takeda. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

In recent years, knowledge about the pathophysiology of inflammatory bowel disease (IBD) has led to the development of novel therapies and biologics with differing mechanisms of action. A major innovation has been the development of small molecules. Tofacitinib was the first pan-Janus kinase (Jak) inhibitor approved for the treatment of IBD, targeting the 4 isoforms of cytokine-associated Jaks (Jak1, Jak2, Jak3, and tyrosine-protein kinase 2). Compared with biologic agents, novel small molecules have a short half-life, a rapid onset of action, and no immunogenicity, but they are associated with a potentially increased risk of off-target side effects. These differences in properties between biologic and oral small molecule therapies may be important when considering their relative treatment positioning and role in clinical practice. Although tofacitinib has been demonstrated to be highly effective as both first- and second-line therapy for ulcerative colitis, concerns about safety, including the risk of infection, venous thromboembolism, major adverse cardiovascular events, and malignancy, have dampened enthusiasm for its widespread use. Subsequently, several Jak inhibitors with more selective profiles, and potentially improved safety while maintaining treatment efficacy, are currently in late-stage clinical trials for use in patients with IBD. This article summarizes the current data regarding the use, safety, and efficacy of Jak inhibitors in patients with IBD., (Copyright © 2022, Gastro-Hep Communications, Inc.)

Background: Data are needed to inform the positioning of biologic therapy in the treatment of moderate-to-severe Crohn's disease, both first line and after previous biologic exposure. We aimed to assess the comparative efficacy and safety of biologics in patients with Crohn's disease., Methods: We did a systematic review and network meta-analysis of phase 2 and phase 3 randomised controlled trials done in adults (≥18 years) with moderate-to-severe Crohn's disease (Crohn's Disease Activity Index [CDAI] 220-450) treated with tumour necrosis factor (TNF) antagonists, anti-integrin, anti-interleukin (IL)-12 and IL-23p40, or anti-IL23p19 agents, either alone or in combination with immunosuppressants, as their first-line biologic or after previous biologic exposure, compared with placebo or an active comparator. The minimum duration of therapy was 14 days for trials reporting induction of remission in active disease and 22 weeks in trials reporting maintenance of remission. We searched Medline, EMBASE, the Cochrane CENTRAL Register of Controlled Trials, conference proceedings, trial registries, and unpublished data from inception to June 3, 2021, without any language restrictions. Summary estimates of the primary and secondary outcomes were extracted from the published reports; individual patient-level data were not sought. The primary endpoint was induction of clinical remission in patients with active disease (CDAI <150) and maintenance of remission in patients with response to induction therapy, with data extracted from published reports. A network meta-analysis with multivariate consistency model random-effects meta-regression was done, with rankings based on surface under the cumulative ranking curve (SUCRA) values., Findings: The search strategy yielded 18 382 citations, of which 31 trials were eligible for inclusion. On the basis of 15 randomised controlled trials including 2931 biologic-naive patients, infliximab monotherapy (odds ratio [OR] 4·53 [95% CI 1·49-13·79]), infliximab combined with azathioprine (7·49 [2·04-27·49]), adalimumab (3·01 [1·25-7·27]), and ustekinumab (2·63 [1·10-6·28]) were associated with significantly higher odds of inducing remission compared to certolizumab pegol (all moderate confidence); infliximab and azathioprine combination therapy was also associated with significantly higher odds of inducing remission than vedolizumab (3·76 [1·01-14·03]; low confidence). On the basis of ten randomised controlled trials including 2479 patients with previous biologic exposure, adalimumab after loss of response to infliximab (OR 2·82 [95% CI 1·20-6·62]; low confidence), and risankizumab (2·10 [1·12-3·92]; moderate confidence), were associated with higher odds of inducing remission than vedolizumab. No differences between active interventions were observed in maintenance trials. Most trials were at low or uncertain risk of bias., Interpretation: Although biologic treatment choices in patients with moderate-to-severe Crohn's disease must be individualised for each patient, this analysis suggests that either infliximab with azathioprine or adalimumab might be preferred as a first-line therapy, and adalimumab (after infliximab loss of response) or risankizumab might be preferred as a second-line therapy, for induction of clinical remission., Funding: None., Competing Interests: Declaration of interests SS has received personal fees from Pfizer for ad hoc grant review, and his institute has received research grants from AbbVie and Janssen. MF has received consulting fees or lecture fees, or both, from AbbVie, Amgen, Ferring, Fresenius Kabi, Janssen, Takeda, Pfizer, Tillots, Celgene, Celltrion, MSD, Biogen, Gilead, and Galapagos; and research support from Pfizer, Sandoz, AbbVie, and Takeda. RS has received consulting fees from Alimentiv. VJ has received consulting and advisory board fees from AbbVie, Alimentiv, Arena Pharmaceuticals, Asieris, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Fresenius Kabi, Galapagos, GlaxoSmithKline, Genetech, Gilead, Janssen, Merck, Mylan, Pandion, Pendopharm, Pfizer, Reistone Biopharma, Roche, Sandoz, Takeda, and Topivert; and speaker's fees from AbbVie, Ferring, Galapagos, Janssen Pfizer Shire, and Takeda. RP has received consulting and advisory board fees from AbbVie, Abbott, Alimentiv, Amgen, Arena Pharmaceuticals, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim Celgene, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead Sciences, GlaxoSmithKline, Janssen, Merck, Mylan, Oppilan Pandion Pharma, Pendopharm, Pfizer, Progenity, Protagonist Therapeutics, Roche, Satisfai Health, Sandoz, Schering-Plough, Shire, Sublimity Therapeutics, Theravance Biopharma, UCB, and Takeda Pharmaceuticals; speaker's fees from AbbVie, Arena Pharmaceuticals, Celgene, Eli Lilly, Ferring, Gilead Sciences, Janssen, Merck, Pfizer, Roche, Sandoz, Shire, and Takeda Pharmaceuticals; and research and educational support from AbbVie, Ferring, Janssen, Pfizer, and Takeda. WJS has received research grants from AbbVie, Abivax, Arena Pharmaceuticals, Boehringer Ingelheim, Celgene, Genentech, Gilead Sciences, GlaxoSmithKline, Janssen, Lilly, Pfizer, Prometheus Biosciences, Seres Therapeutics, Shire, Takeda, and Theravance Biopharma; consulting fees from AbbVie, Abivax, Admirx, Alfasigma, Alimentiv, Alivio Therapeutics, Allakos, Amgen, Applied Molecular Transport, Arena Pharmaceuticals, Bausch Health (Salix), Beigene, Bellatrix Pharmaceuticals, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Myers Squibb, Celgene, Celltrion, Cellularity, Cosmo Pharmaceuticals, Escalier Biosciences, Equillium, Forbion, Genentech–Roche, Gilead Sciences, Glenmark Pharmaceuticals, Gossamer Bio, Immunic (Vital Therapies), Index Pharmaceuticals, Intact Therapeutics, Janssen, Kyverna Therapeutics, Landos Biopharma, Lilly, Oppilan Pharma (acquired by Ventyx Biosciences), Otsuka, Pandion Therapeutics, Pfizer, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonists Therapeutics, Provention Bio, Reistone Biopharma, Seres Therapeutics, Shanghai Pharma Biotherapeutics, Shire, Shoreline Biosciences, Sublimity Therapeutics, Surrozen, Takeda, Theravance Biopharma, Thetis Pharmaceuticals, Tillotts Pharma, UCB, Vendata Biosciences, Ventyx Biosciences, Vimalan Biosciences, Vivelix Pharmaceuticals, Vivreon Biosciences, and Zealand Pharma; stock or stock options from Allakos, BeiGene, Gossamer Bio, Oppilan Pharma (acquired by Ventyx Biosciences), Prometheus Biosciences, Prometheus Laboratories Progenity, Shoreline Biosciences, Ventyx Biosciences, Vimalan Biosciences, and Vivreon Biosciences; and an employee at Shoreline Biosciences. WJS' spouse is an employee at Prometheus Biosciences and a consultant at Iveric Bio, Oppilan Pharma (acquired by Ventyx Biosciences), and Prometheus Laboratories; and holds stocks or stock options, or both, in Iveric Bio, Progenity, Oppilan Pharma (acquired by Ventyx Biosciences), Prometheus Biosciences, Prometheus Laboratories, Ventyx Biosciences, and Vimalan Biosciences. CM has received consulting fees from AbbVie, Amgen, AVIR Pharma, Bristol Myers Squibb, Ferring, Fresenius Kabi, Janssen, McKesson, Mylan, Takeda, Pfizer, Roche, Alimentiv; and speaker's fees from AbbVie, Amgen, AVIR Pharma, Janssen, Takeda, and Pfizer; and research support from Pfizer. MHM declares no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)