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Efficacy of Linaclotide in Reducing Abdominal Symptoms of Bloating, Discomfort, and Pain: A Phase 3B Trial Using a Novel Abdominal Scoring System.
Am J Gastroenterol. 2021 09 01; 116(9):1929-1937.AJ

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+Show Affiliations

David Geffen School of Medicine at UCLA, Los Angeles, California, USA.Mayo Clinic, Jacksonville, Florida, USA.University of North Carolina, Atrium Health, Charlotte, North Carolina, USA.Northwestern Medicine Digestive Health Center, Chicago, Illinois, USA.AbbVie Inc, Madison, New Jersey, USA.Formerly Employed at Ironwood Pharmaceuticals, Inc, Boston, Massachusetts, USA.Ironwood Pharmaceuticals, Inc, Boston, Massachusetts, USA.AbbVie Inc, Madison, New Jersey, USA.Formerly Employed at AbbVie Inc, Madison, New Jersey, USA.AbbVie Inc, Madison, New Jersey, USA.AbbVie Inc, Madison, New Jersey, USA.Formerly Employed at Ironwood Pharmaceuticals, Inc, Boston, Massachusetts, USA. Cyclerion Therapeutics, Cambridge, Massachusetts, USA.Ironwood Pharmaceuticals, Inc, Boston, Massachusetts, USA.Ironwood Pharmaceuticals, Inc, Boston, Massachusetts, USA.Formerly Employed at Ironwood Pharmaceuticals, Inc, Boston, Massachusetts, USA.

Pub Type(s)

Clinical Trial, Phase III
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

34465695

Citation

Chang, Lin, et al. "Efficacy of Linaclotide in Reducing Abdominal Symptoms of Bloating, Discomfort, and Pain: a Phase 3B Trial Using a Novel Abdominal Scoring System." The American Journal of Gastroenterology, vol. 116, no. 9, 2021, pp. 1929-1937.
Chang L, Lacy BE, Moshiree B, et al. Efficacy of Linaclotide in Reducing Abdominal Symptoms of Bloating, Discomfort, and Pain: A Phase 3B Trial Using a Novel Abdominal Scoring System. Am J Gastroenterol. 2021;116(9):1929-1937.
Chang, L., Lacy, B. E., Moshiree, B., Kassebaum, A., Abel, J. L., Hanlon, J., Bartolini, W., Boinpally, R., Bochenek, W., Fox, S. M., Mallick, M., Tripp, K., Omniewski, N., Shea, E., & Borgstein, N. (2021). Efficacy of Linaclotide in Reducing Abdominal Symptoms of Bloating, Discomfort, and Pain: A Phase 3B Trial Using a Novel Abdominal Scoring System. The American Journal of Gastroenterology, 116(9), 1929-1937. https://doi.org/10.14309/ajg.0000000000001334
Chang L, et al. Efficacy of Linaclotide in Reducing Abdominal Symptoms of Bloating, Discomfort, and Pain: a Phase 3B Trial Using a Novel Abdominal Scoring System. Am J Gastroenterol. 2021 09 1;116(9):1929-1937. PubMed PMID: 34465695.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Efficacy of Linaclotide in Reducing Abdominal Symptoms of Bloating, Discomfort, and Pain: A Phase 3B Trial Using a Novel Abdominal Scoring System. AU - Chang,Lin, AU - Lacy,Brian E, AU - Moshiree,Baha, AU - Kassebaum,Amy, AU - Abel,Jessica L, AU - Hanlon,Jennifer, AU - Bartolini,Wilmin, AU - Boinpally,Ramesh, AU - Bochenek,Wieslaw, AU - Fox,Susan M, AU - Mallick,Madhuja, AU - Tripp,Ken, AU - Omniewski,Nicholas, AU - Shea,Elizabeth, AU - Borgstein,Niels, PY - 2020/11/10/received PY - 2021/05/14/accepted PY - 2021/9/1/entrez PY - 2021/9/2/pubmed PY - 2021/9/14/medline SP - 1929 EP - 1937 JF - The American journal of gastroenterology JO - Am J Gastroenterol VL - 116 IS - 9 N2 - 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. SN - 1572-0241 UR - https://www.unboundmedicine.com/medline/citation/34465695/Efficacy_of_Linaclotide_in_Reducing_Abdominal_Symptoms_of_Bloating_Discomfort_and_Pain:_A_Phase_3B_Trial_Using_a_Novel_Abdominal_Scoring_System_ L2 - https://doi.org/10.14309/ajg.0000000000001334 DB - PRIME DP - Unbound Medicine ER -