OBJECTIVES: A systematic literature review (SLR) and network meta-analysis (NMA) were conducted in order to compare linaclotide with other oral medications for the treatment of chronic constipation.

METHODS: MEDLINE, ICHUSHI, Cochrane CENTRAL, and ClinicalTrials.gov were systematically searched up to August 8, 2017. Eligible studies were randomized controlled trials of 43 oral drugs approved around the world for adult patients with chronic functional constipation, including irritable bowel syndrome with constipation and opioid-induced constipation. Change from baseline in weekly number of spontaneous bowel movements (SBM) was used as an efficacy endpoint. Mean differences (MD) of SBM were compared between linaclotide 500 mcg versus other treatments. The Bayesian hierarchical methodology was used for the NMA.

RESULTS: From 1,577 references, the SLR identified 54 trials including four trials by hand searching. Totally, 47 treatments/16 drugs (different doses of the same drug were defined as separate treatments) including placebo were incorporated in the NMA. Linaclotide 500 mcg showed higher improvement of SBM change than placebo (MD: -1.906; 95% credible interval: -2.672, -1.197), lubiprostone 16 mcg (-1.903 [-3.254, -0.704]), methylnaltrexone 450 mg (-1.407 [-2.796, -0.003]) and tegaserod 12 mg (-1.023 [-1.909, -0.182]), but was less effective than linaclotide 600 mcg (non-marketed dose, 1.156 [0.025, 2.281]) and bisacodyl 10 mg (2.997 [1.652, 4.359]). In point-estimate terms, linaclotide 500 mcg was more effective than lubiprostone 32 mcg and 48 mcg, plecanatide 3 mg and 6 mg, polyethylene glycol 5.9 g to 26 g, prucalopride 1 mg to 4 mg, lactulose 10 g and 20 g, and lactitol 10 g and 20 g.

CONCLUSIONS: Linaclotide 500 mcg was superior to placebo, low-dose of lubiprostone (16 mcg), methylnaltrexone and tegaserod, but inferior to bisacodyl and higher dose of linaclotide (600 mcg) in terms of improvement of SBM change.