Efficacy and Safety of Peripherally Acting Mu-Opioid Receptor Antagonists for the Treatment of Opioid-Induced Constipation: A Bayesian Network Meta-analysis.

Abstract

To assess the efficacy and safety of peripherally acting mu-opioid receptor antagonists (PAMORAs) for the treatment of opioid-induced constipation (OIC). Randomized controlled trials (RCTs) were searched for OIC therapy comparing PAMORAs with placebo. Both a pairwise and network meta-analysis were performed. The surface under the cumulative ranking area (SUCRA) was used to determine the efficacy and safety of OIC treatment using different PAMORAs. The primary target outcome was a response that achieves an average of three or more bowel movements (BMs) per week. In the network meta-analysis, four PAMORAs (naldemedine, naloxone, methylnaltrexone, and alvimopan) showed a better BM response than the placebo. Naldemedine was ranked first (odds ratio [OR] = 2.8, 95% credible interval [CrI] = 2-4.5, SUCRA = 89.42%), followed by naloxone (OR = 2.9, 95% CrI = 1.6-5.3, SUCRA = 87.44%), alvimopan (OR = 2.2, 95% CrI = 1.3-3.5, SUCRA = 68.02%), and methylnaltrexone (OR = 1.7, 95% CrI = 1.0-2.8, SUCRA = 46.09%). There were no significant differences in safety found between the PAMORAs and the placebo. We found that PAMORAs are effective and can be safely used for the treatment of OIC. In network meta-analysis, naldemedine and naloxone appear to be the most effective PAMORAs for the treatment of OIC.