Effects of treatment with eluxadoline on abdominal pain in patients with IBS‐D: Additional post hoc analyses of Phase 3 trials

Abstract

Background Recurring abdominal pain is a characteristic and often unpredictable and debilitating symptom of irritable bowel syndrome with diarrhea (IBS‐D). Measuring the effects of IBS‐D treatments on abdominal pain remains a significant challenge in clinical trials. Here, we aimed to examine the effect of eluxadoline through various post hoc analyses. Methods Data from two eluxadoline Phase 3 trials were pooled over 26 weeks, comparing eluxadoline 100 mg twice daily to placebo. Worst abdominal pain (WAP) was measured daily on a 0‐10 scale. WAP responder criteria were prospectively defined as a ≥30% improvement in daily WAP score on ≥50% of days. Pairwise, two‐sided Cochran‐Mantel‐Haenszel tests assessed treatment effects. Cumulative distribution functions were used to plot WAP response rates using variations on the response criteria. Key results Of 1615 patients with IBS‐D (66% female, mean age 46 years), 806 received eluxadoline and 809 received placebo; 48.3% and 44.0% were WAP responders (≥30% improvement), respectively (P value not significant). When the response threshold was increased to 50% daily WAP improvement from baseline, a significantly greater percentage of eluxadoline‐treated patients versus placebo‐treated patients were WAP responders (38.7% vs 32.5%, respectively; P = .009). At Week 26, average WAP changes from baseline were −3.4 and −3.0 points, respectively (P = .002). Conclusions and Inferences Despite small effect sizes, eluxadoline demonstrated consistent and sustained improvement in WAP compared to placebo across a range of prospective and post hoc analyses. Assessing WAP response across a range of measures is important for fully understanding a treatment's efficacy.

Efficacy and safety of olorinab, a full agonist of the cannabinoid receptor 2, for the treatment of abdominal pain in patients with irritable bowel syndrome: Results from a phase 2b randomized placebo‐controlled trial (CAPTIVATE)

“…The United States Food and Drug Administration defines a clinically significant abdominal pain "response" to therapy in patients with IBS as a ≥ 30% decrease in patient-reported weekly average worst daily pain for ≥6 weeks for a 12-week treatment period. 29 However, many patients with IBS have failed to meet this criterion for improvement in abdominal pain in pivotal randomized controlled trials of new therapeutic agents targeting IBS-C and IBS-D. [30][31][32] Effective, long-lasting, and well-tolerated treatment of abdominal pain is therefore an unmet need in IBS. 13,14 Olorinab may offer a well-tolerated, novel approach to abdominal pain management in IBS.…”

Review article: current and future treatment approaches for IBS with constipation

“…Eluxadoline has been reported in post hoc analyses to improve abdominal pain and bowel symptoms in several clinical trials. [41][42][43] Further paediatric studies are forthcoming (NCT04880876, NCT03339128).…”