Eluxadoline Versus Antispasmodics in the Treatment of Irritable Bowel Syndrome: An Adjusted Indirect Treatment Comparison Meta-analysis

Objective: Eluxadoline is a newly approved drug for irritable bowel syndrome (IBS), but it has rarely been compared with positive controls. We aimed to compare eluxadoline with antispasmodics in the treatment of IBS. Methods: We searched the OVID Medline, Embase, and the Cochrane Central Register of Controlled Trials databases for randomized controlled trials (RCTs) comparing eluxadoline or antispasmodics with placebo. The search was conducted from 1 January 1980, to 1 September 2020, without any language restrictions. The primary efficacy outcome was the relief of abdominal pain, defined by a reduction of pain scores of at least 30% from baseline. The secondary efficacy outcome was the relief of global IBS symptoms, defined by a composite response of a decrease in abdominal pain and improvement in stool consistency on the same day for at least 50% of the days assessed. The data were pooled using a random-effects model. Outcome estimates were pooled by using Risk Ratios (RRs) and P-scores. Results: Forty-two trials with 8,457 participants were included from 45 articles. Compared with placebo, each of drotaverine, pinaverium, alverine combined with simethicone (ACS) and eluxadoline 100 mg was highly effective in the relief of abdominal pain, with drotaverine [RR, 2.71 (95% CI, 1.70 to 4.32), P-score = 0.95] ranking first. Drotaverine, otilonium, cimetropium, pinaverium, and eluxadoline 100 mg had significantly high the relief of global IBS symptomss, for which drotaverine [RR, 2.45 (95% CI, 1.42 to 4.22), P-score = 0.95] was ranked first. No significant difference was found between these interventions. Pinaverium had a significantly higher the relief of global IBS symptoms than eluxadoline [RR, 1.72 (95% CI, 1.33 to 2.21)] on sensitivity analysis. However, no significant difference was found in the number of adverse events between each intervention and the placebo. Conclusion: Our network meta-analysis showed that eluxadoline 100 mg was at least as effective as antispasmodics in relieving abdominal pain in IBS. But eluxadoline had more reported adverse events. Antispasmodics are still the first choice for the treatment of IBS.