Comparative effectiveness of 5-hydroxytryptamine 3 receptor antagonists in irritable bowel syndrome: a network meta-analysis of randomized controlled studies

BACKGROUND: There is evidence demonstrating the beneficial effects of 5-hydroxytryptamine 3 receptor antagonists (5-HT(3)) for the treatment of non-constipated irritable bowel syndrome (NC-IBS). We aimed to determine the comparative effectiveness of 5-HT(3) antagonists in NC-IBS, as evidenced by the results of a network meta-analysis (NWM) of published relevant randomized controlled trials (RCTs). METHODS: We searched the PubMed/Medline, EMBASE, and Cochrane Library databases for relevant RCTs through September 2020 and data from each selected RCT were extracted. A Bayesian NWM was then performed to investigate the efficacy of 5-HT(3) antagonists and to explore the effectiveness rank order in treating NC-IBS patients. RESULTS: Twenty-one eligible RCTs were identified and entered into this NWM. They included a total of 10,421 NC-IBS patients, randomized to alosetron, cilansetron, ondansetron, ramosetron, placebo, and mebeverine. The cumulative ranking probability for each intervention at the end of treatment period, was evaluated by means of surfaces under cumulative ranking (SUCRA) values. These results showed that alosetron had the best performance for global symptom improvement (SUCRA 0.82), cilansetron showed the best performance (SUCRA 0.90) for abdominal pain/discomfort improvement, while ondansetron (SUCRA 0.98) was by far the best choice concerning bowel habits/consistency improvement. The control regimens (mebeverine and placebo) represented the least efficacious interventions. CONCLUSIONS: This NWM showed that 5-HT(3) receptor antagonists performed better in comparison to control drugs. Consequently, this class of drugs may play an important role in improving the debilitating symptoms in NC-IBS patients, in particular those with diarrhea.