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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.)

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.)

Restorative proctocolectomy with ileal pouch-anal anastomosis is an option for most patients with ulcerative colitis or familial adenomatous polyposis who require colectomy. Although the construction of an ileal pouch substantially improves patients' health-related quality of life, the surgery is, directly or indirectly, associated with various structural, inflammatory, and functional adverse sequelae. Furthermore, the surgical procedure does not completely abolish the risk for neoplasia. Patients with ileal pouches often present with extraintestinal, systemic inflammatory conditions. The International Ileal Pouch Consortium was established to create this consensus document on the diagnosis and classification of ileal pouch disorders using available evidence and the panellists' expertise. In a given individual, the condition of the pouch can change over time. Therefore, close monitoring of the activity and progression of the disease is essential to make accurate modifications in the diagnosis and classification in a timely manner., 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. 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 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. JP 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–Syneors, Check-Cap, Dizal Pharmaceuticals GalenPharma–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, 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, Evidera. SV reports consultancy 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, Tillots Pharma AG, and grants from AbbVie, Johnson & Johnson, Pfizer, and Takeda. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)