P5098 - 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

Darren M.. Brenner, MD¹, Blesson George, PharmD², Adam P.. Laitman, MD², Yuying Luo, MD³
1Northwestern University Feinberg School of Medicine, Chicago, IL, US, Chicago, IL; 2Salix Pharmaceuticals, Bridgewater, NJ; 3Mount Sinai West & Morningside, New York, NY

Introduction: IBS-C is a burdensome condition that negatively impacts HR-QOL. In trial settings, the 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 two 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.

Discussion: 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.

Disclosures:
Darren Brenner: Alnylam Pharmaceuticals – Advisor or Review Panel Member, Consultant, Speaker. Anji Pharma, Ardelyx – Advisor or Review Panel Member. Ardelyx, AbbVie, Ironwood Pharmaceuticals, Bayer, Blueprint Medicines, CinPhloro Pharma, Dr Reddy’s Laboratories, Gemelli Biotech, Laborie – Consultant. Ardelyx, AbbVie, Ironwood Pharmaceuticals, Salix Pharmaceuticals – Speakers Bureau. Entrinsic Bioscience – Advisor or Review Panel Member, Consultant, Speaker. International Foundation for GI Disorders – Advisory Committee/Board Member. Mahana Therapeutics, Owlstone Medical, Salix Pharmaceuticals, Vibrant Pharma – Consultant. Takeda Pharmaceuticals – Advisor or Review Panel Member, Consultant, Speaker. Vibrant Gastro – Advisor or Review Panel Member, Consultant, Speaker.
Blesson George: Salix Pharmaceuticals – Employee.
Adam Laitman: Salix Pharmaceuticals – Employee.
Yuying Luo: Ardelyx – Grant/Research Support.

Darren M.. Brenner, MD¹, Blesson George, PharmD², Adam P.. Laitman, MD², Yuying Luo, MD³. P5098 - 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, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.