Annual Scientific Meeting
Introduction: The efficacy and safety of eluxadoline (ELX), a US Food and Drug Administration-approved mixed μ- and κ-opioid receptor agonist and δ-opioid receptor antagonist for treating adult patients with irritable bowel syndrome with diarrhea (IBS-D), were evaluated in patients who self-reported inadequate response to loperamide in the RELIEF trial. Radar plots were generated from these results to interpret improvements across a spectrum of efficacy measures in ELX-treated patients.
Methods: A Phase 4, multicenter, placebo (PBO)-controlled, double-blind study randomized patients with IBS-D (Rome III criteria) with intact gallbladders who reported overall inadequate IBS symptom control with loperamide in the preceding 12 months to oral ELX (100 mg twice daily) or PBO for 12 weeks (RELIEF; NCT02959983). Patients rated IBS symptoms including worst abdominal pain (WAP), abdominal bloating, abdominal discomfort, stool consistency, number of bowel movements (BMs), and urgency episodes daily. Adequate relief of IBS symptoms was assessed weekly. Response rates over Weeks 1–12 and change from baseline to Week 12 were graphed using radar plots for the following endpoints: primary efficacy composite response (simultaneous daily improvement of ≥ 40% in WAP score vs. baseline and Bristol Stool Form Scale score < 5 [or no BM] on ≥ 50% of treatment days); stool consistency response as per the primary endpoint; urgency-free response calculated using criteria of ≥ 50% or ≥ 75% of days with no urgency episodes; adequate relief response defined as a weekly “yes” response for ≥ 50% of treatment weeks; WAP response calculated using criteria of ≥ 30%, ≥ 40%, or ≥ 50% improvement vs. baseline.
Results: In this study cohort, baseline symptom scores were similar between the treatment groups (Table). Significantly higher proportions of ELX-treated patients were composite, stool consistency, and ≥ 30%, ≥ 40%, and ≥ 50% WAP responders vs. PBO at Week 12 (Figure 1). A greater proportion of ELX- vs. PBO-treated patients were also urgency-free and adequate relief responders. ELX-treated patients experienced greater improvements from baseline in WAP, abdominal bloating and discomfort, BM frequency, and urgency episodes vs. PBO (Figure 2).
Discussion: Across 13 endpoints, ELX treatment led to improvements vs. PBO, indicating efficacy across a multitude of IBS-D symptoms among patients with prior inadequate symptom control with loperamide.