Efficacy of Secretagogues in Patients With Irritable Bowel Syndrome With Constipation: Systematic Review and Network Meta-analysis

Background & Aims: Several secretagogues have been approved treatment of irritable bowel syndrome with constipation (IBS-C). However, their relative efficacy is unclear because there have been no head-to-head randomized controlled trials. We conducted a network meta-analysis to compare their efficacies in patients with IBS-C.

Methods: We searched MEDLINE, EMBASE, EMBASE Classic, and the Cochrane central register of controlled trials through June 2018 to identify randomized controlled trials assessing the efficacy of secretagogues in adults with IBS-C. Trials included in the analysis reported a dichotomous assessment of overall response to therapy, and data were pooled using a random effects model. Efficacy and safety of secretagogues were reported as a pooled relative risk with 95% CIs to summarize the effect of each comparison tested, and treatments were ranked according to their P-score.

Results: We identified 15 eligible randomized controlled trials of secretagogues, containing 8462 patients. Linaclotide, lubiprostone, plecanatide, and tenapanor were all superior to placebo for the treatment of IBS-C. Linaclotide (290 mcg, once daily) was ranked first in efficacy, based on the Food and Drug Administration-recommended endpoint for trials in IBS-C, the primary endpoint used in each trial, abdominal pain, and complete spontaneous bowel movements. Tenapanor (50 mg twice daily) was ranked first for reducing bloating. Total numbers of adverse events were significantly greater with linaclotide (290 mcg, once daily and 500 mcg, once daily) and plecanatide (3 mg, once daily) compared with placebo. However, 6 mg, once-daily plecanatide ranked first for safety. Diarrhea was significantly more common with all drugs, except lubiprostone (8 mcg, twice daily). Nausea was significantly more common among patients who received lubiprostone.

Conclusions: In a network analysis of randomized controlled trials of secretagogues for IBS-C, we found all drugs to be superior to placebo. Efficacy was similar among individual drugs and dosages for most endpoints. However, data were extracted at the 12-week time point, so the long term relative efficacy of these drugs is unknown.