Efficacy and safety of linaclotide in patients with irritable bowel syndrome with constipation: Chinese sub-cohort analysis of a phase III, randomized, double-blind, placebo-controlled trial

Li Hua Peng, Jing Yuan Fang, Ning Dai, Xi Zhong Shen, You Lin Yang, Jing Sun, Yun Sheng Yang, Li Hua Peng, Jing Yuan Fang, Ning Dai, Xi Zhong Shen, You Lin Yang, Jing Sun, Yun Sheng Yang

Abstract

Objective: To conduct a sub-cohort analysis to evaluate the efficacy and safety of linaclotide in Chinese patients with constipation-predominant irritable bowel syndrome (IBS-C) using data from a completed trial (NCT01880424).

Methods: In this phase III, double-blind, placebo-controlled trial, IBS-C patients were randomized to receive linaclotide (290 μg/d) or placebo for 12 weeks. Efficacy was assessed with two co-primary responder end-points (12-wk abdominal pain/discomfort: ≥30% reduction in either score with neither deteriorating from baseline for ≥6 wks; 12-wk IBS degree of relief: score ≤2 for ≥ 6 wks), seven secondary endpoints and several additional end-points.

Results: In total, 659 Chinese IBS-C patients received linaclotide (n = 327) or placebo (n = 332). The 12-week abdominal pain/discomfort end-point was met in 62.1% and 53.3% of the linaclotide-treated and placebo-treated patients, respectively (odds ratio [OR] 1.43, 95% confidence interval [CI] 1.05-1.96, P = 0.023); the 12-week IBS degree of relief end-point was achieved in 32.7% and 16.9% of the patients treated with linaclotide and placebo, respectively (OR 2.40, 95% CI 1.66-3.47, P < 0.001). The linaclotide-treated patients had a shorter time to the first spontaneous bowel movement than the placebo-treated patients (23.6 h vs 43.7 h, P < 0.001). Linaclotide produced significantly greater improvement than placebo in all secondary end-points from the first 2 weeks (all P < 0.001). Diarrhea was reported in 8.3% of linaclotide-treated patients and 1.2% of placebo-treated patients.

Conclusion: Linaclotide (290 μg/d) was efficacious and well-tolerated in Chinese IBS-C patients with a rapid onset of effect.

Keywords: abdominal pain; constipation; guanylate cyclase; irritable bowel syndrome; linaclotide.

Conflict of interest statement

None.

© 2022 The Authors. Journal of Digestive Diseases published by Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

Figures

FIGURE 1
FIGURE 1
Flowchart of patient recruitment and randomization
FIGURE 2
FIGURE 2
A, Incremental 12‐week complete spontaneous bowel movement (CSBM) responder end‐point. P < 0.05 at each level of increase, except for an increase of ≥6 (P = 0.052) and ≥7 (P = 0.149). B, Incremental 12‐week abdominal pain responder end‐point. P < 0.05 at each level of increase. C, Incremental 12‐week abdominal discomfort responder end‐point. P < 0.05 at each level of increase, except for an increase of ≥40% (P = 0.168), ≥50% (P = 0.073) and ≥70% (P = 0.164). Statistical analysis was performed using the Cochran‐Mantel‐Haenszel test. ▪▪▪ Linaclotide 290 μg/d; ▪▪▪ placebo

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