Lembo AJ¹, Covington PS², Dove LS³, Andrae DA³. Neurogastroenterol Motil. 2020 Apr;32(4):e13774. doi: 10.1111/nmo.13774. Epub 2020 Jan 27.

Author information

1 Harvard Medical School, Boston, MA, USA.

2 Former employee of Furiex Pharmaceuticals, Inc., an affiliate of Allergan plc, Madison, NJ, USA.

3 Former employee of Allergan plc, Madison, NJ, USA.

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.