Patients with opioid-induced bowel disorders (OIBD) who received methylnaltrexone had a decreased all-cause mortality risk of 60% compared with those who received placebo, according to a study in Pain Medicine.
The findings are based on a posthoc pooled analysis of 12 randomized placebo-controlled clinical trials that evaluated the all-cause mortality risk in patients treated with methylnaltrexone for OIBD.
The participants had noncancer pain or advanced illness and received subcutaneous, intravenous, or oral methylnaltrexone or matching placebo in the studies. All-cause mortality was defined as the number of patients who died 30 days or less after the final medication dose in the double-blind phase of each study. The duration of mortality follow-up ranged from about 1 to 4 months.
The analysis included 2526 patients (mean age, 55.0 years; women, 54.4%) who received methylnaltrexone and 1192 who received placebo (mean age, 57.1 years; women, 53.9%). Overall, 33 deaths were reported in the patients who received methylnaltrexone, and 35 deaths occurred in the patients who received placebo.
The reduction in all-cause mortality risk among patients treated with methylnaltrexone compared with placebo was significant at 60% (univariable hazard ratio [HR], 0.399; 95% CI, 0.248, 0.643; P =.0002). The mortality rate was 17.8 deaths per 100 person-years of exposure (PYE) for methylnaltrexone and 49.5 deaths per 100 PYE for placebo. After adjustments for cancer status, age group, and sex, a persistently significant attenuation of risk was observed (HR, 0.508; 95% CI, 0.314, 0.820; P =.0056).
Patients with cancer who received placebo had a significant increase in all-cause mortality vs those who received methylnaltrexone (HR, 0.470; 95% CI, 0.267, 0.827, P =.0089). Participants aged younger than 60 years who received methylnaltrexone had a 79% mortality risk reduction vs those who received placebo (HR, 0.210; 95% CI, 0.077, 0.567; P =.0021).
Women who received methylnaltrexone had a 66% decrease in mortality risk compared with women who received placebo (HR, 0.340; 95% CI, 0.173, 0.670; P =.0018). Men who received methylnaltrexone had a 53% reduction in mortality risk vs those who received placebo (HR, 0.467; 95% CI, 0.238, 0.918; P =.0272).
In patients who had a chronic diagnosis, including cancer and chronic noncancer pain, those who received methylnaltrexone had a 68.5% reduction in mortality risk compared with those who received placebo (HR, 0.315; 95% CI, 0.185, 0.537; P <.0001).
Study limitations include the retrospective design, variability in drug dose, duration and route of administration, limited data on opioid requirements, and the inability to follow participants after prespecified time limits.
“The results of this study demonstrate a statistically and clinically significant reduction in all-cause mortality among patients receiving MNTX [methylnaltrexone] for treatment of opioid-induced constipation [OIC], with consistent effects observed in patients with cancer or chronic diagnoses, independent of age and gender,” the study authors wrote. “We hypothesize that MNTX may provide protective benefit against the additional mortality risk associated with opioid treatment in patients with chronic diagnoses and OIC.”
Disclosure: The study was funded by Salix Pharmaceuticals, a division of Bausch Health US, LLC. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Webster LR, Brenner D, Israel RJ, Stambler N, Slatkin NE. Reductions in all-cause mortality associated with the use of methylnaltrexone for opioid-induced bowel disorders: a pooled analysis. Pain Med. Published online September 14, 2022. doi:10.1093/pm/pnac136