Comparative Efficacy of Linaclotide Versus Other Oral Constipation Treatments in Chronic Constipation: a Network Meta-analysis

Abstract

This systematic literature review and network meta-analysis (NMA) indirectly compared the Japanese standard dose of linaclotide 500 μg with other oral chronic constipation (CC) treatments. PubMed, Cochrane-CENTRAL, Ichushi-Web, and ClinicalTrials.gov were systematically searched for eligible randomized controlled trials of 43 oral drugs approved globally for CC, including irritable bowel syndrome with constipation (IBS-C) and opioid-induced constipation (OIC). The mean difference (95% credible interval) in change from baseline in weekly number of spontaneous bowel movements (SBM) was compared between linaclotide 500 μg (unapproved in OIC) and other treatments using Bayesian methodology. Fifty-two publications (54 trials) involving 47 treatments (16 drugs, different doses of the same drug treated as different treatments) were included in the NMA. Despite including various drugs/doses, for the mean difference in weekly SBM change, linaclotide 500 μg was statistically significantly more efficacious than other drugs/doses (vs 500 μg linaclotide) including the following: placebo (− 1.907; − 2.568, − 1.237); lubiprostone 16 μg (− 2.090; − 3.226, − 0.968); methylnaltrexone 150 mg (− 1.807; − 3.126, − 0.491), 300 mg (− 1.411; − 2.722, − 0.096), and 450 mg (− 1.405; − 2.708, − 0.097); naloxegol 5 mg (− 2.074; − 4.001, − 0.131) and 12.5 mg (− 1.329; − 2.347, − 0.318); and tegaserod 4 mg (− 1.133; − 2.059, − 0.207) and 12 mg (− 1.024; − 1.822, −0.228), and statistically significantly less effective than linaclotide 600 μg non-approved dose (1.159; 0.123, 2.199) and bisacodyl 10 mg (2.979; 1.723, 4.233). These findings provide relative efficacy data for linaclotide 500 μg vs other constipation drugs/doses regarding improving weekly SBM in CC and IBS-C and may inform clinical decision-making for constipation treatments.