Effects of Linaclotide in Patients With Irritable Bowel Syndrome With Constipation or Chronic Constipation: A Meta-analysis

BACKGROUND & AIMS: Linaclotide is a minimally absorbed, 14 amino acid peptide used to treat patients with irritable bowel syndrome with constipation (IBS C) or chronic constipation (CC). We per formed a meta analysis to determine the efficacy of linaclotide, compared with placebo, for patients with IBS C or CC. METHODS: MEDLINE, EMBASE, and the Cochrane central register of controlled trials were searched for randomized, placebo controlled trials examining the effect of linaclotide in adults with IBS C or CC. Dichotomous results were pooled to yield a relative risk (RR), 95% confidence intervals (CIs), and number needed to treat (NNT). RESULTS: The search identified 7 trials of linaclotide in patients with IBS C or CC; 6 were included in the analysis. Two of 3 trials of IBS C used the end point recommended by the U. S. Food and Drug Administration: an increase from baseline of 1 or more complete spontaneous bowel movement (CSBM)/week and a 30% or more reduction from baseline in the weekly average of daily worst abdominal pain scores for 50% of the treatment weeks. On the basis of this end point, the RR for response to treatment with 290 mu g linaclotide, compared with placebo, was 1.95 (95% CI, 1.3-2.9), and the NNT was 7 (95% CI, 5 11). For CC, on the basis of data from 3 trials of patients with CC, the RR for the primary end point (more than 3 CSBMs/week and an increase in 1 or more CSBM/week, for 75% of weeks) was 4.26 for 290 mu g linaclotide vs placebo (95% CI, 2.80-6.47), and the NNT was 7 (95% CI, 5 8). Linaclotide also improved stool form and reduced abdominal pain, bloating, and overall symptom severity in patients with IBS C or CC. CONCLUSIONS: On the basis of a meta analysis, linaclotide improves bowel function and reduces abdominal pain and overall severity of IBS C or CC, compared with placebo.