Durability and Predictability of Treatment Response to Lubiprostone in Patients With Constipation-Predominant Irritable Bowel Syndrome

Abstract

Introduction: Lubiprostone is a ClC-2 chloride channel activator with demonstrated efficacy and safety for treating symptoms of constipation-predominant irritable bowel syndrome (IBS-C). The objective of this analysis was to examine whether an early treatment response could predict a durable response in patients who received lubiprostone treatment (8 mcg twice daily) or placebo in pivotal IBS-C studies. Methods: Data were pooled from two 12-week, randomized, placebo-controlled, double-blind, phase 3 studies in adults ≥18 years of age meeting Rome II criteria for IBS-C. Treatment response analyses were conducted using the intent-to-treat population, and the response durability was analyzed in patients who had a response in week 1 (weekly responders) or month 1 (monthly responders) of the study. A weekly responder was defined as a patient with symptoms that were rated as “moderately relieved” or “significantly relieved” within a given week. A monthly responder was defined as having symptoms rated as “moderately relieved” for all 4 weeks or “significantly relieved” for ≥2 weeks within a given month, with no ratings of “moderately worse” or “significantly worse,” and no increase in the percentage of days of rescue medication during the month as compared with baseline. Results: The initial response rate in patients who were week 1 responders was 73.5% (100/136) in patients treated with lubiprostone vs 56.9% (33/58) in patients who received placebo (P=0.0178, Cochran-Mantel-Haenszel [CMH] test). The between-group difference in response in week 1 responders was significantly higher with lubiprostone compared with placebo over the entire treatment period (P=0.0018, generalized estimating equation [GEE] model). Further, among month 1 responders, patients who were treated with lubiprostone vs those who received placebo maintained responses in month 2 (67.1% vs 48.0%, respectively) and month 3 (46.1% vs 20.0%, respectively; overall difference: P=0.0236, GEE model). Conclusion: Pooled data from IBS-C pivotal studies suggest that an early response with lubiprostone (as early as week 1) in patients with IBS-C is predictive of a durable treatment response compared with patients who received placebo.