S1217 Improvement in Health-Related Quality of Life (HR-QOL) in Adults With Irritable Bowel Syndrome With Constipation (IBS-C) Not Achieving Bowel Movement Frequency Criterion: Analysis of Two Phase 3 Plecanatide Trials

Introduction: Irritable bowel syndrome with constipation (IBS-C) is a burdensome condition that negatively impacts health-related quality of life (HR-QOL). In trial settings, the US Food and Drug Administration (FDA) recommends that an IBS-C composite response to therapy include a ≥1 complete spontaneous bowel movement (CSBM) increase from baseline per week for ≥50% of treatment time (eg, ≥6 of 12 weeks). As some patients do not meet this individual criterion of the composite endpoint but may experience other benefits, the aim was to evaluate improvement in HR-QOL in a subset of patients with IBS-C who did not meet the FDA CSBM frequency criterion in a trial setting. Methods: Data were pooled from 2 phase 3 randomized, double-blind, placebo-controlled trials of adults with IBS-C (Rome III). This post hoc analysis included patients treated with plecanatide 3 mg or placebo who did not have an increase from baseline of ≥1 CSBM per week for ≥6 of 12 weeks (ie, CSBM nonresponders) during the trials. Symptoms (eg, abdominal pain [range, 0-10]) and CSBM occurrence were recorded daily. The Irritable Bowel Syndrome Quality of Life (IBS-QOL) questionnaire was administered at baseline (Day 1) and Weeks 4, 8, 12 (end of treatment), and 14, with a minimally clinically important difference (MCID) in IBS-QOL validated as a ≥14-point improvement from baseline. P value for MCID was calculated using Cochran–Mantel–Haenszel, stratified by gender. Least-square mean changes from baseline were analyzed using analysis of covariance (effect of treatment and baseline as covariate). Results: 928 patients (plecanatide [n = 428; 72.0% female]; placebo [n = 500; 74.0% female]) were included. Mean (SD) age in the plecanatide vs placebo groups was 43.4 (14.0) vs 43.3 (14.2), and mean IBS-QOL score was 47.4 (25.6) vs 45.8 (24.7). Baseline mean score was 6.5 vs 6.4 for abdominal pain, and mean number of CSBMs/week was 0.2 for both groups. A significantly greater percentage of CSBM nonresponders had a clinically meaningful improvement in the IBS-QOL total score at Week 12 in the plecanatide vs placebo groups (36.9% vs 28.8%; P < 0.01). Larger numeric improvements from baseline at Week 12 in 7 of the 8 IBS-QOL subdomains (ie, dysphoria, food avoidance, interference with activity, body image, health worry, relationship, and social reaction) were observed in plecanatide vs placebo groups, although differences were not statistically significant. Conclusion: Patients with IBS-C treated with plecanatide may experience meaningful improvement in IBS-QOL irrespective of whether the stringent FDA clinical trial criterion of CSBM response is met.