Summary 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.

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 4 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% 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 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.

Commentary - Both authors contributed equally