Efficacy of Linaclotide in Reducing Abdominal Symptoms of Bloating, Discomfort, and Pain: A Phase 3B Trial Using a Novel Abdominal Scoring System.

Abstract

INTRODUCTION:

Linaclotide improves abdominal pain and constipation in patients with constipation-predominant irritable bowel syndrome (IBS-C). Patients report additional bothersome abdominal symptoms of bloating and discomfort. The intention of this study was to evaluate linaclotide's efficacy in relieving IBS-C-related abdominal symptoms (bloating, discomfort, and pain) using a novel multi-item Abdominal Score (AS).

METHODS:

Patients with IBS-C with abdominal pain ≥3 (0-10 scale) were randomized to linaclotide 290 μg or placebo daily for 12 weeks. The AS, derived from the Diary for IBS Symptoms-Constipation, is the average of abdominal bloating, discomfort, and pain at their worst (0 = none, 10 = worst possible). The primary end point was overall change from baseline (CFB) in AS. Secondary end points included CFB in 12-week AS evaluated using cumulative distribution function and 6-week/12-week AS responder (AS improvement ≥2 points for ≥6-week/12-week).

RESULTS:

Overall, 614 patients (mean age 46.7 years; 81% female) were randomized. All prespecified end points showed significant benefit of linaclotide vs placebo. The mean overall CFB AS reduction for linaclotide was -1.9 vs -1.2 for placebo (P < 0.0001); the 6-week/12-week AS responder rate was 40.5% for linaclotide vs 23.4% for placebo (odds ratio = 2.2 [95% confidence interval, 1.55-3.12; P < 0.0001]). Diarrhea was the most common treatment-emergent adverse event (linaclotide = 4.6%, placebo = 1.6%).

DISCUSSION:

Linaclotide significantly reduced multiple abdominal symptoms important to patients with IBS-C (bloating, discomfort, and pain) compared with placebo, as measured by a novel multi-item AS. The AS, derived from the Diary for IBS Symptoms-Constipation, should be considered for use in future IBS-C clinical studies to measure clinically meaningful improvements beyond traditional end points.

• Authors: Lin Chang, Brian E Lacy, Baha Moshiree, Amy Kassebaum, Jessica L Abel, Jennifer Hanlon, Wilmin Bartolini, Ramesh Boinpally, Wieslaw Bochenek, Susan M Fox, Madhuja Mallick, Ken Tripp, Nicholas Omniewski, Elizabeth Shea, Niels Borgstein
• Journal: The American journal of gastroenterology (Am J Gastroenterol) Vol. 116 Issue 9 Pg. 1929-1937 (09 01 2021) ISSN: 1572-0241 [Electronic] United States
• PMID: 34465695 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.

Chemical References

• Gastrointestinal Agents
• Guanylyl Cyclase C Agonists
• Peptides
• linaclotide

Topics

• Abdominal Pain (drug therapy)
• Adult
• Constipation (drug therapy)
• Double-Blind Method
• Female
• Gastrointestinal Agents (therapeutic use)
• Guanylyl Cyclase C Agonists (therapeutic use)
• Humans
• Male
• Middle Aged
• Peptides (therapeutic use)
• Severity of Illness Index
• Treatment Outcome