Su1386 Clinical Benefit and Intestinal Mucosal Transcriptome Modulation After Long-Term Mast Cell Stabilization With Oral Disodium Cromoglycate in Diarrhea-Predominant Irritable Bowel Syndrome (IBS-D) Patients

Abstract

Introduction: Irritable bowel syndrome with diarrhea (IBS-D) is a chronic, functional gastrointestinal disorder with symptoms of abdominal pain and diarrhea that significantly impact health-related quality of life (HRQoL). Eluxadoline is an investigational, locally active, mixed mu opioid receptor agonist and delta opioid receptor antagonist that significantly improved both pain and diarrhea in two Phase 3 IBS-D trials (IBS3001 and IBS3002). Aim: To evaluate the impact of eluxadoline treatment on HRQoL in patients with IBS-D in two Phase 3 trials. Methods: Adults meeting Rome III criteria for IBS-D were randomized to twice-daily oral treatment with eluxadoline (75 or 100 mg) or placebo for 26 weeks in IBS3002 and 52 weeks in IBS3001. The Irritable Bowel Syndrome Quality of Life (IBS-QOL) questionnaire, which consists of 34 items, each with a 5-point response scale (1=not at all, 5=extremely or a great deal), was completed at baseline and Weeks 4, 8, 12, 18, and 26 in both trials, and at Week 30 in IBS3002 and Weeks 36, 44, and 52 in IBS3001. Mean IBS-QOL overall scores were evaluated for trends by treatment groups by employing a longitudinal mixedeffects polynomial model fitted to pooled data to estimate treatment effects of eluxadoline. Cumulative distribution functions for changes from baseline to Weeks 12, 26, and 52 in IBS-QOL overall scores were plotted. Results: The longitudinal mixed-effects model showed a significant treatment main effect (t=4.45, p<0.0001) for the eluxadoline 100 mg treatment group. Similar results were observed for the 75 mg treatment group. Patients treated with eluxadoline 100 mg showed consistently higher IBS-QOL scores over 52 weeks of treatment compared with patients who received placebo (Figure 1). Cumulative distribution function plots of change from baseline scores confirmed that patients treated with eluxadoline 100 mg showed consistently higher increases in IBS-QOL overall scores compared with patients who received placebo over a range of improvement levels for Weeks 12, 26, and 52 (Figure 2). Conclusions: Compared with placebo, twice-daily eluxadoline treatment significantly improved overall HRQOL among IBS-D patients over the course of the treatment periods in two Phase 3 trials as measured by the IBS-QOL, with patients treated with eluxadoline 100 mg showing particularly strong effects.