{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T22:52:58Z","timestamp":1783119178598,"version":"3.54.6"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T00:00:00Z","timestamp":1663113600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Salix Pharmaceuticals"},{"name":"Bausch Health US"},{"name":"Lantheus Holdings, Inc."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Preclinical and clinical studies suggest that activation of the \u00b5-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 \u00b5-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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The risk of all-cause mortality within 30\u2009days 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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\u2009=\u2009.0002), 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.1093\/pm\/pnac136","type":"journal-article","created":{"date-parts":[[2022,9,13]],"date-time":"2022-09-13T20:14:36Z","timestamp":1663100076000},"page":"341-350","source":"Crossref","is-referenced-by-count":3,"title":["Reductions in All-Cause Mortality Associated with the Use of Methylnaltrexone for Opioid-Induced Bowel Disorders: A Pooled Analysis"],"prefix":"10.1093","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8609-9424","authenticated-orcid":false,"given":"Lynn 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