Impact of Treatment Response on Quality of Life and Work Productivity among Patients with Irritable Bowel Syndrome with Constipation or Chronic Constipation: Pooled Results from Phase III Clinical Trials

Abstract

Purpose: To assess the impact of treatment response on quality of life (QOL) and work productivity for patients with irritable bowel syndrome with constipation (IBS-C) or chronic constipation (CC). Methods: Irritable Bowel Syndrome QOL (IBS-QOL) score, EQ-5D score, work productivity, symptom relief, and treatment satisfaction data were collected in phase III randomized placebo-controlled clinical trials of linaclotide, a new treatment for IBS-C and CC. Treatment response for IBS-C was defined as (1) a ≥ 14-point increase in the IBS-QOL overall score from baseline to Week 12 or (2) one of the top two responses (moderately or significantly relieved) in ≥2 out of 3 months on a seven-point Likert scale assessing IBS symptom relief. Response for CC was defined as having (1) one of the top two responses (quite or very satisfied) on a five-point Likert scale assessing treatment satisfaction or (2) having a weekly spontaneous bowel movement (SBM) frequency ≥4 at Week 12. Hours of work missed due to IBS-C or CC were collected using the Work Productivity and Activity Impairment (WPAI) questionnaire. Data from the intent-to-treat populations were pooled for linaclotide and placebo across two trials per condition. EQ-5D and work productivity outcomes were evaluated among responders and non-responders. Results: Approximately 1,500 and 1,200 subjects with available EQ-5D data and 1,100 and 800 with available WPAI data were analyzed from IBS-C and CC trials, respectively. Responders had statistically significantly higher Week 12 EQ-5D scores than non-responders, for all definitions (IBS-QOL: 0.85 vs. 0.81, IBS symptom relief: 0.91 vs. 0.81, CC treatment satisfaction: 0.91 vs. 0.86, CC SBM: 0.90 vs. 0.86; all P<0.05). Responders were statistically significantly less likely to miss ≥1 hour of work during 12 weeks for IBS-C (IBS-QOL: 16.0% vs. 21.7%, IBS symptom relief: 9.6% vs. 20.8%, both P<0.05), but not CC (treatment satisfaction: 7.7% vs. 10.6%, P=0.16; SBM: 8.82% vs. 10.0%, P=0.56). Conclusion: Improvements in disease-specific measures correlate with improvements in health utilities and, to a lesser extent, reduced work absenteeism. Disclosure: Huan Huang and Joseph Menzin: employees of Boston Health Economics, a consultancy whose activities related to this project are funded by Forest Laboratories, Inc., and Ironwood Pharmaceuticals, Inc.; Robyn Carson: employee of Forest Laboratories, Inc. and owns stock and/or stock options in Forest Laboratories, Inc.; Phil Sarocco and Doug Taylor: employees of Ironwood Pharmaceuticals, Inc. and own stock and/or stock options in Ironwood Pharmaceuticals. This research was supported by an industry grant from Forest Laboratories, Inc., and Ironwood Pharmaceuticals, Inc., were involved in the study design; collection, analysis and data interpretation; and decision to submit these data for presentation. Study was sponsored by Forest Laboratories, Inc., and Ironwood Pharmaceuticals, Inc.