Efficacy and safety of medical therapies in microscopic colitis: a systematic review and network meta-analysis

Background:The mainstay of treatment for microscopic colitis (MC) is budesonide. However, the optimal formulation and dosage of budesonide to induce and maintain remission has not yet been clearly demonstrated. Objectives:To compare the data for efficacy and safety of treatments to induce and maintain remission for MC. Design:We conducted a meta-analysis of randomised controlled trials (RCTs) comparing treatment with each other or placebo for induction and maintenance of clinical and histological remission in MC. Data sources and methods:We searched MEDLINE (1946 to May 2021), EMBASE and EMBASE Classis (1947 to May 2021), the Cochrane central register of controlled trials (Issue 2, May 2021) and conference proceedings between 2006 and 2020. Results were reported as pooled relative risks (RRs) with 95% confidence intervals (CIs) to summarise the effect of each comparison tested, with treatments ranked according to p score. Results:We identified 15 RCTs in total for the treatment of MC. Entocort 9 mg ranked first for clinical (RR: 4.89, CI: 2.43-9.83; p score: 0.86) and histological (RR: 13.39, CI: 1.92-93.44; p score 0.94) induction of remission, whilst VSL#3 ranked second for clinical induction (RR: 5.30, CI: 0.68-41.39; p score 0.81). Budenofalk 6 mg/3 mg alternate day dosing ranked first for clinical maintenance of remission (RR: 3.68, CI: 0.08-159.92, p-score 0.65). Entocort and Budenofalk were associated with the greatest adverse events for induction and maintenance of clinical remission, respectively, although the overall withdrawal numbers for treatment versus placebo groups were 10.9% (22/201) and 10.5% (20/190), respectively. Conclusion:Entocort 9 mg/day ranked first among the treatment options in inducing remission and Budenofalk 6 mg/3 mg alternate day dosing for maintaining remission in the treatment of MC. Moving forward, mechanistic studies exploring the differences between Entocort and Budenofalk would be valuable whilst future RCT studies are needed in non-corticosteroidal maintenance, particularly looking into immunomodulators, biologics and probiotics.