D0266 - Rifaximin Improves Both Fecal Urgency and Stool Consistency in Adults With Irritable Bowel Syndrome With Diarrhea (IBS-D): A Composite Endpoint Analysis of Two Randomized, Phase 3 Trials

Introduction: For patients with IBS-D, in addition to loose stool consistency, fecal urgency is a common, bothersome symptom. The aim was to evaluate rifaximin for simultaneously improving symptoms of fecal urgency in addition to loose/watery stool consistency as a unique composite bowel symptom endpoint.

Methods: A post hoc analysis was conducted with data from 2 identically designed, phase 3, randomized, double-blind trials. Adults with IBS-D, with screening daily mean stool consistency score of ≥3.5 (range, 1 “very hard”; 5 “watery”), took rifaximin 550 mg TID or placebo for 2 weeks, followed by a 4-week treatment-free phase to assess response. Fecal urgency was based on patient response to the daily question, “Have you felt or experienced a sense of urgency today?” Composite bowel symptom responders were defined as patients who simultaneously achieved a ≥30% decrease from baseline in the percentage of days with fecal urgency and had a mean weekly stool consistency score of < 4 for ≥2 of the first 4 post-treatment weeks. Data were analyzed using last observation carried forward; P values were calculated using the Cochran-Mantel-Haenszel method, adjusting for analysis center.

Results: A total of 1258 adults (rifaximin [n=624], placebo [n=634]) were included (mean ± SD age, 45.9 ± 14.5 years; 72.3% female). Similar values at baseline were observed for rifaximin and placebo groups for the percentage of days with fecal urgency (82%), mean daily stool consistency score (3.9), and mean ± SD number of daily bowel movements (3.0 ± 1.5). A significantly greater percentage of patients treated with rifaximin were bowel symptom composite responders vs placebo for ≥2 of the first 4 weeks post-treatment (47.9% vs 39.3%, respectively; P=0.002). A higher percentage of responders with rifaximin was observed vs placebo when analyzed by week (Figure). A significantly higher percentage of patients who were bowel symptom composite responders during ≥2 of the first 4 weeks post-treatment maintained response during ≥3 of the additional 6 weeks of treatment-free follow up (Week 12) in rifaximin vs placebo groups (44.7% vs 36.1%; P=0.002). For the individual components of response, a significantly greater percentage of patients in rifaximin group were fecal urgency responders vs placebo (52.9% vs 43.1%; P< 0.001) or stool consistency responders (82.7% vs 77.8%; P=0.03).

Discussion: A 2-week course of rifaximin significantly and simultaneously improved fecal urgency and stool consistency vs placebo in adults with IBS-D.