Linaclotide for Treatment of IBS-C and Chronic Constipation

Orlando—There are limited options available for the treatment of irritable bowel syndrome with constipation (IBS-C). The FDA recently approved linaclotide for the treatment of IBS-C and functional constipation.

Researchers recently conducted a meta-analysis of existing clinical trials to determine the efficacy and safety of varying daily doses of oral linaclotide in management of IBS-C and chronic constipation. They reported results of the analysis in a poster session during Digestive Disease Week 2013 in Orlando, Florida. The poster was titled Effect of Linaclotide in the Treatment of Irritable Bowel Syndrome and Chronic Constipation: A Meta-Analysis.

In November 2012, the researchers conducted a systematic search of PubMed, CINAHL, Scopus, and the Cochrane Database of Systematic Reviews, as well as the ClinicalTrials.gov registry. Two independent reviewers identified prospective, randomized controlled trials published in English comparing the effect of oral linaclotide versus placebo in adults with IBS-C and chronic constipation.

The primary outcome of ≥3 complete spontaneous bowel movements (CSBMs) per week and an increase of at least 1 CSBM per week from baseline was determined using a random effects model. The secondary outcome was frequency of adverse events.

Subgroup analysis was performed by dividing the studies into 2 groups: (1) patients receiving 290-300 mcg of linaclotide daily (high-dose group) and (2) patients receiving 145-150 mcg of linaclotide daily (low-dose group).

The literature search identified 6 studies that met inclusion criteria. The 6 eligible studies involved a total of 3644 patients. The mean percentage of patients who reached the primary end point was 9% (n=1375) in the placebo group and 22% (n=2227) in the linaclotide group.

For the primary outcome of CSBM, there was a statistically significant improvement in the linaclotide group compared with the placebo group (odds ratio [OR] 3.42; 95% confidence interval [CI], 2.06-5.68; P<.01). For the secondary outcome, there was a statistically significant increase in adverse events compared with placebo (OR 1.28; 95% CI, 1.11-1.48; P<.01).

Results of the subgroup analysis demonstrated that a daily dose of 145-150 mcg of linaclotide demonstrated a statistically significant improvement in CSBM (OR 3.50; 95% CI, 1.92-6.38; P<.01) compared with placebo. There was also an increase in adverse events in the 145-150 mcg group compared with the placebo group (OR 1.39; 95% CI, 1.09-1.76; P<.01).

In the high-dose group, there was a statistically significant improvement in CSBM (OR 3.84; 95% CI, 2.20-6.69; P<.01) compared with placebo. There was also an increase in adverse events in the high-dose group compared with placebo (OR 1.24; 95% CI, 1.07-1.45; P<.01).

In summary, the researchers stated, “Linaclotide appears to be effective in the treatment of IBS-C and chronic constipation, however, linaclotide has more adverse events, which do not appear to be dose-related. Given the limited options in the treatment of IBS-C and chronic constipation, linaclotide seems to be a viable option.”