Effects of linaclotide in the treatment of chronic constipation and irritable bowel syndrome with constipation: a meta-analysis.

Abstract

OBJECTIVE:

Linaclotide is a guanylate cyclase-C (GCC) agonist that is found in intestinal epithelial cells and is used when treating chronic constipation (CC) and irritable bowel syndrome with constipation (IBS-C). Several randomized controlled trials (RCTs) were conducted for evaluating its efficacy and safety.

METHODS:

The PubMed, EMBASE, and Cochrane databases and the Web of Science were searched to find multiple RCTs of patients with CC or IBS-C. The Jadad scoring system was used for evaluating each study's methodological quality, and RevMan5.3 was used for meta-analysis. The composite endpoint reaction approved by the FDA, abdominal pain and discomfort relief, symptom improvement, and diarrhea-related adverse reactions were chosen as observation indicators, and relative risk (RR) and 95% confidence interval (CI) were obtained for quantitative and comprehensive evaluation.

RESULTS:

Eleven randomized controlled studies were included, consisting of 5 cases of CC and 6 cases of IBS-C. Linaclotide reached the composite endpoint response approved by FDA in the treatment of CC (RR = 3.26, 95% CI: 2.45-4.33), and the composite endpoint response approved by FDA for the treatment of IBS-C (RR = 2.26, 95% CI: 1.86-2.74) was greater than the placebo (both p < 0.00001). The main adverse reactions of linaclotide were gastrointestinal, mostly diarrhea, which was higher than that of the placebo when treating CC (RR = 3.56, 95% CI: 2.76-4.60) and IBS-C (RR = 8.23, 95% CI: 5.69-11.90) (both p < 0.00001).

CONCLUSION:

Linaclotide proved to be effective and safe for the treatment of CC and IBS-C compared to the placebo. However, diarrhea is the primary adverse reaction.

• Authors: Qi Zhao, Yongkun Fang, Cheng Yan, Jing Gao, Zhuangzhuang Liu, Hanjian Zhu, Dong Tang, Daorong Wang
• Journal: Zeitschrift fur Gastroenterologie (Z Gastroenterol) Vol. 60 Issue 6 Pg. 970-977 (Jun 2022) ISSN: 1439-7803 [Electronic] Germany
• Vernacular Title: Wirkungen von Linaclotid bei der Behandlung von chronischer Verstopfung und Reizdarmsyndrom mit Verstopfung: eine Metaanalyse.
• PMID: 34215016 (Publication Type: Journal Article, Meta-Analysis)
• Copyright: Thieme. All rights reserved.

Chemical References

• Peptides
• linaclotide

Topics

• Constipation (drug therapy)
• Diarrhea (chemically induced, drug therapy)
• Humans
• Irritable Bowel Syndrome (complications, drug therapy)
• Peptides
• Treatment Outcome