Rifaximin and eluxadoline - newly approved treatments for diarrhea-predominant irritable bowel syndrome: what is their role in clinical practice alongside alosetron?

INTRODUCTION: Diarrhea-predominant irritable bowel syndrome (IBS-D) is a common functional gastrointestinal condition in which patients experience abdominal pain, diarrhea, bloating, cramps, flatulence, fecal urgency, and incontinence. AREAS COVERED: We review two recently approved therapies that focus on treating underlying pathogenic mechanisms of IBS-D: (1) the non-absorbable antibiotic rifaximin, and (2) the opioid receptor agonist/antagonist eluxadoline. We compare the safety and efficacy data emerging from rifaximin and eluxadoline registration trials with safety and efficacy data from the alosetron clinical development program. EXPERT OPINION: The rifaximin and eluxadoline clinical development programs for IBS-D have demonstrated significant improvement in IBS-D endpoints compared to placebo. Direct comparison of primary endpoint results from the alosetron, rifaximin, and eluxadoline pivotal trials is not possible; however, general estimates of efficacy can be made, and these demonstrate similar and significantly greater responses to 'adequate relief' and a composite endpoint of abdominal pain/stool form for each agent compared to placebo. With the recent approval in the United States of rifaximin and eluxadoline for IBS-D, how should clinicians employ these agents? We suggest that they be utilized sequentially, taking into consideration patient symptoms and severity, prior medical history, mode of action, cost, availability, managed care coverage, and adverse event profiles.