Effect of Linaclotide in the Treatment of Irritable Bowel Syndrome and Chronic Constipation: a Meta-Analysis

Background: Irritable Bowel Syndrome with Constipation (IBS-C) and functional constipation are common gastrointestinal disorders with limited treatment options. We performed a meta-analysis to estimate the efficacy of different daily doses of oral linaclotide in the management of IBS-C and chronic constipation. Methods: A search was performed in May 2014. A meta-analysis was performed on randomized controlled trials comparing linaclotide versus placebo to assess the primary outcome (three or more Complete Spontaneous Bowel Movement (CSBM) per week and an increase of at least one CSBM per week from baseline) and secondary outcome (frequency of adverse events). Subgroup analysis was performed by dividing the studies into a high-dose group (290-300 mcg) and low-dose group (145-150 mcg). Results: Six studies (N=3,654) were included. Linaclotide demonstrated a statistically significant improvement as compared to placebo (OR 3.42; 95% CI: 2.06-5.68; p<0.01) for CSBM. However, linaclotide showed a statistically significant increase in adverse events as compared to placebo (OR 1.28; 95% CI: 1.12-1.48; p<0.01). In subgroup analysis, linaclotide of 145-150 mcg and 290-300 mcg demonstrated statistically significant improvements in CSBM (OR 3.81; 95% CI: 2.55-5.70; p<0.01 and OR 3.84; 95% CI: 2.20-6.69; p<0.01, respectively) as compared to placebo. However, linaclotide of 145-150 mcg and 290-300 mcg revealed a statistically significant increase in adverse events (OR 1.39; 95% CI: 1.09-1.76; p<0.01 and OR 1.24; 95% CI: 1.07-1.45; p<0.01, respectively) as compared to placebo. Conclusion: Linaclotide appears to be effective in the treatment of IBS-C and chronic constipation but has more adverse events.