Efficacy and Safety of Eluxadoline in Patients With Irritable Bowel Syndrome With Diarrhea Who Report Inadequate Symptom Control With Loperamide: RELIEF Phase 4 Study.

OBJECTIVES: Irritable bowel syndrome with diarrhea (IBS-D) is a functional gastrointestinal disorder with limited effective treatment options. We evaluated the efficacy and safety of eluxadoline in patients with IBS-D who reported inadequate symptom control with prior loperamide. METHODS: Three hundred forty-six adults with IBS-D (Rome III criteria) were randomly assigned to placebo or eluxadoline 100 mg twice daily for 12 weeks. Patients recorded daily IBS-D symptoms, including worst abdominal pain (WAP) and stool consistency (through Bristol Stool Scale). The primary endpoint was proportion of composite responders, defined as patients who met daily composite response criteria (>= 40% WAP improvement and <5 Bristol Stool Scale score) for at least 50% of treatment days, and recorded >= 60 days of diary entries over the 12-week period. RESULTS: Over 12 weeks, a significantly greater proportion of eluxadoline patients achieved the primary composite responder endpoint compared to placebo (22.7% vs 10.3%, P = 0.002), and component endpoints of improvements in stool consistency (27.9% vs 16.7%, P = 0.01) and WAP (43.6% vs 31.0%, P = 0.02). Additionally, a greater proportion of eluxadoline patients met the composite responder endpoint assessed at monthly intervals compared to placebo (weeks 1-4: 14.0% vs 6.9%, P = 0.03; weeks 5-8: 26.7% vs 14.9%, P = 0.006; weeks 9-12: 30.8% vs 16.7%, P = 0.002). Rates of adverse events were comparable in both groups (37.4% vs 35.3%); no treatment-related serious adverse event, cases of sphincter of Oddi spasm, or pancreatitis were reported. DISCUSSION: Eluxadoline appears safe and effective for treating IBS-D symptoms in patients with an intact gallbladder reporting inadequate relief with prior loperamide use.