Determining the optimal treatment target in patients with ulcerative colitis: rationale, design, protocol and interim analysis for the randomised controlled VERDICT trial.

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.

Systematic review and meta-analysis of randomised controlled trials: Medical therapies for the treatment and prevention of pouchitis.

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.

An Expert Consensus to Standardize Assessment of Bowel Cleansing for Clinical Trials of Bowel Preparations for Crohn's Disease.

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.

REMIT-UC: Real-World Effectiveness and Safety of Tofacitinib for Moderate-to-Severely Active Ulcerative Colitis: A Canadian IBD Research Consortium Multicenter National Cohort Study.

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.

Placebo Response Rates in Randomized Controlled Trials for Perianal Crohn's Disease: A Systematic Review and Meta-Analysis.

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.

Comparison of the Relative Sensitivity of Clinical, Endoscopic, and Histologic Remission for Detection of Treatment Efficacy in Ulcerative Colitis Trials.

This systemic review and quantitative analysis of placebo-controlled ulcerative colitis (UC) induction trials found higher pooled histologic remission rates compared with clinical and endoscopic remission rates at the same timepoint, and no significant differences in pooled relative risks for these outcomes between treatment groups; supporting the concept that histologic remission is not less sensitive than clinical or endoscopic remission.

Clinical, Endoscopic, and Radiological Effectiveness of Ustekinumab in Bio-naïve Versus Bio-experienced Patients With Crohn's Disease: Real-world Experience From a Large Canadian Center.

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.

In this large real-world study of patients with Crohn's Disease treated with ustekinumab, we observed high rates of clinical, endoscopic, radiological, and biochemical response and remission rates. Effectiveness was greater in bio-naïve compared with bio-experienced patients.

Placebo Rates in Randomized Controlled Trials of Proctitis Therapy: A Systematic Review and Meta-Analysis Placebo Response in Proctitis.

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.

Immunotherapy for Cancer: Common Gastrointestinal, Liver, and Pancreatic Side Effects and Their Management.

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.

Janus Kinase Inhibitors for the Management of Patients With Inflammatory Bowel Disease.

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.

Effectiveness of Tofacitinib for Hospitalized Patients with Acute Severe Ulcerative Colitis: Case Series.

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.

Similar Clinical Improvement Rates Among Biologic Drug Classes in Crohn's Disease: Systematic Review and Meta-Regression.

We conducted a systematic review and metaregression of pivotal Crohn's disease trials to evaluate the rates of change in Crohn's Disease Activity Index scores in patients receiving biologic treatments. The speed of clinical improvement was similar among biologic drug classes.

Underrepresentation of Minorities and Lack of Race Reporting in Ulcerative Colitis Drug Development Clinical Trials.

Historically, inflammatory bowel disease trials report high rates of White patients enrollment. To promote initiatives toward diversifying the enrolled population, we assessed the reporting of race and ethnicity of patients enrolled in pharmaceutical clinical trials for ulcerative colitis.

The Relationship Between Endoscopic and Clinical Recurrence in Postoperative Crohn's Disease: A Systematic Review and Meta-analysis.

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.

Systematic Review and Meta-Analysis: Clinical, Endoscopic, Histological and Safety Placebo Rates in Induction and Maintenance Trials of Ulcerative Colitis.

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.

Disease Activity Indices for Pouchitis: A Systematic Review.

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.

Clinical, Endoscopic, and Safety Placebo Rates in Induction and Maintenance Trials of Crohn's Disease: Meta-Analysis of Randomised Controlled Trials.

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.

Treatment of pouchitis, Crohn's disease, cuffitis, and other inflammatory disorders of the pouch: consensus guidelines from the International Ileal Pouch Consortium.

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.