Efficacy and Safety of Peripherally Acting Mu-Opioid Receptor Antagonists for the Treatment of Opioid-Induced Constipation: A Bayesian Network Meta-analysis
Rong Ouyang, Zhongzhuan Li, Shijiang Huang, Jun Liu, Jiean Huang
Abstract
OBJECTIVE: To assess the efficacy and safety of peripherally acting mu-opioid receptor antagonists (PAMORAs) for the treatment of opioid-induced constipation (OIC). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.