P0398 - Plecanatide Provided Clinically Meaningful Improvements in Health-Related Quality of Life in Patients With Chronic Idiopathic Constipation and Irritable Bowel Syndrome With Constipation: A Post-Hoc Analysis
Northwestern University Feinberg School of Medicine Chicago, IL, United States
Darren M. Brenner, MD1, Eric Shah, MD, MBA2, Christopher Chang, MD, PhD3, Kelly Chong, PhD4, Sarah Lorenzen, PhD5, Gregory S. Sayuk, MD, MPH6 1Northwestern University Feinberg School of Medicine, Chicago, IL; 2Dartmouth-Hitchcock Health, Lebanon, NH; 3University of New Mexico School of Medicine, New Mexico VA Health Care System, Albuquerque, NM; 4University of New Mexico School of Medicine, Albuquerque, NM; 5Salix Pharmaceuticals, Bridgewater Township, NJ; 6Washington University School of Medicine, John Cochran Veterans Affairs Medical Center, St. Louis, MO
Introduction: Chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C) significantly impact health-related quality of life (QOL). This post hoc analysis evaluated the impact of plecanatide vs placebo on health-related QOL across four phase 3 trials (2 in CIC; 2 in IBS-C).
Methods: Patients with CIC or IBS-C were randomized to once-daily plecanatide 3 mg (PLE), or placebo (PBO). Patients with CIC completed the Patient Assessment of Constipation (PAC)-QOL (28 items rated from 0 [not at all] to 4 [extremely/all the time]; 4 domains). Patients with IBS-C completed the IBS-QOL (34 items rated from 1 [not at all] to 5 [extremely/a great deal]; 8 domains). Both measures were administered on Day 1 and at Weeks 4, 8, and 12; higher scores indicate poorer QOL. Response was defined based on prevous research establishing minimal meaningful improvement as a ≥1-point reduction in PAC-QOL or a ≥14-point reduction in IBS-QOL score from baseline.
Results: 1762 patients with CIC (PBO, n=885; PLE, n=877) and 1453 with IBS-C (PBO, n=729; PLE, n=724) received PBO or PLE in the intention-to-treat populations. Significantly more PLE vs PBO patients reported a ≥1-point reduction in PAC-QOL (31.7% vs 23.7%; P< 0.001) and ≥14-point reduction in IBS-QOL (44.3% vs 33.2%; P< 0.001). Total score improvements from baseline to Week 12 were greater with plecanatide than placebo for PAC-QOL (least-squares mean change: PBO -0.85, PLE -1.09; P< 0.001) and IBS-QOL (PBO -14.8, PLE -17.9; P< 0.05). PAC-QOL domain scores at Week 12 showed significant improvements in satisfaction, worries/concerns, and physical discomfort compared to PBO (Figure 1A); IBS-QOL domain scores showed significant improvements in dysphoria, body image, food avoidance, social reaction, and relationship items (Figure 1B). Changes in PAC-QOL at Week 12 were weakly to moderately correlated with changes in bowel movements and changes in abdominal pain (Pearson r=0.30-.040; P< 0.0001). Changes in IBS-QOL at Week 12 were more weakly correlated with changes in bowel movements and changes in abdominal pain (r=0.17-0.28; P< 0.0001).
Discussion: Across two CIC and two IBS-C phase 3 trials, plecanatide 3 mg led to significant, clinically meaningful improvements in QOL compared to PBO. The correlation coefficients suggest that resolution of a single symptom alone does not drive improvements in QOL. Rather it appears that multi-symptom management is necessary to improve patients’ QOL
Figure: Figure 1. Percent of Patients Reporting a (A) ≥1-point reduction in PAC-QOL and (B) ≥14-point reduction in IBS-QOL
Darren M. Brenner, MD1, Eric Shah, MD, MBA2, Christopher Chang, MD, PhD3, Kelly Chong, PhD4, Sarah Lorenzen, PhD5, Gregory S. Sayuk, MD, MPH6. P0398 - Plecanatide Provided Clinically Meaningful Improvements in Health-Related Quality of Life in Patients With Chronic Idiopathic Constipation and Irritable Bowel Syndrome With Constipation: A Post-Hoc Analysis, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.
