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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.

Background and aim Clostridium difficile infection [CDI] is a significant concern in inflammatory bowel disease [IBD]. Risk factors and consequences associated with CDI in inflammatory bowel disease [IBD] patients are important to characterize. The aim of this research was to perform a systematic review and meta-analysis on risk factors and outcomes associated with CDI in IBD patients. Methods Multiple databases were searched for studies investigating risk factors, colectomy and mortality risk in IBD patients with and without CDI. This was stratified by short [ 1 year] outcomes. Summary estimates were calculated using a random-effects model. Quality assessment used the Newcastle-Ottawa scale. Results Twenty-two studies met inclusion criteria. Antibiotics use within 30 days of diagnosis was associated with CDIs (odds ratio [OR]: 1.85, 95% confidence interval [CI]:1.36, 2.52). Colonic involvement in Crohn's disease patients was associated with significantly higher CDI rates [OR: 2.76, 95% CI: 1.75, 4.35]. There was a significant association between biologic medication use and CDI [OR: 1.65, 95% CI: 1.18, 2.30], with minimal heterogeneity [I2 = 4.0%]. The long-term colectomy risk was significantly higher for IBD patients with CDI compared with that for IBD patients without CDI [OR: 2.22, 95% CI: 1.17, 4.18]. Significantly higher mortality was found for CDI in IBD patients both short-term [OR: 3.84, 95% CI: 2.62, 5.61] and long-term [OR: 3.65, 95% CI: 1.58, 8.44]. Substantial heterogeneity existed. Most studies were of moderate quality. Conclusion Colonic involvement, and biologic and antibiotic use appear to be risk factors associated with CDI among IBD patients. CDI is associated with increased short- and long-term mortality.