Reductions in All-Cause Mortality Associated with the Use of Methylnaltrexone for Opioid-Induced Bowel Disorders: A Pooled Analysis

Pain Med. 2023 Mar 1;24(3):341-350. doi: 10.1093/pm/pnac136.

Abstract

Objective: Preclinical and clinical studies suggest that activation of the µ-opioid receptor may reduce overall survival and increase the risk for all-cause mortality in patients with cancer and noncancer pain. Methylnaltrexone, a selective, peripherally acting µ-opioid receptor antagonist, has demonstrated efficacy for the treatment of opioid-induced constipation. This retrospective analysis of 12 randomized, double-blind, placebo-controlled studies of methylnaltrexone evaluated the treatment of opioid-induced bowel disorders in patients with advanced illness or noncancer pain.

Methods: The risk of all-cause mortality within 30 days after the last dose of study medication during the double-blind phase was compared between methylnaltrexone and placebo groups. The data were further stratified by cancer vs noncancer, age, gender, and acute vs chronic diagnoses.

Results: Pooled data included 2,526 methylnaltrexone-treated patients of which 33 died, and 1,192 placebo-treated patients of which 35 died. The mortality rate was 17.8 deaths/100 person-years of exposure in the methylnaltrexone group and 49.5 deaths/100 person-years of exposure for the placebo group. The all-cause mortality risk was significantly lower among patients receiving methylnaltrexone compared with placebo (hazard ratio: 0.399, 95% confidence interval: 0.25, 0.64; P = .0002), corresponding to a 60% risk reduction. Significant risk reductions were observed for those receiving methylnaltrexone who had cancer or chronic diagnoses. Methylnaltrexone-treated patients had a significantly reduced mortality risk compared with placebo regardless of age or gender.

Conclusions: Methylnaltrexone reduced all-cause mortality vs placebo treatment across multiple trials, suggesting methylnaltrexone may confer survival benefits in patients with opioid-induced bowel disorders taking opioids for cancer-related or chronic noncancer pain.

Keywords: Methylnaltrexone; Mortality; Opioid Analgesia; Survival.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics, Opioid* / therapeutic use
  • Chronic Pain* / drug therapy
  • Constipation / chemically induced
  • Double-Blind Method
  • Humans
  • Naltrexone
  • Narcotic Antagonists
  • Randomized Controlled Trials as Topic
  • Retrospective Studies

Substances

  • methylnaltrexone
  • Analgesics, Opioid
  • Naltrexone
  • Narcotic Antagonists