Subcutaneous Methylnaltrexone for Treatment of Opioid-Induced Constipation in Cancer versus Noncancer Patients: An Analysis of Efficacy and Safety Variables from Two Studies.

Methylnaltrexone inhibits opioid-induced constipation (OIC) by binding to peripheral µ-opioid receptors without impacting central opioid receptor mediated analgesia. This analysis compared methylnaltrexone efficacy and safety among advanced illness patients with and without active cancer and OIC. This post hoc analysis included two multicenter, randomized, double-blind, placebo-controlled studies in adults with advanced illness and OIC who received subcutaneous methylnaltrexone. Efficacy endpoints included the proportion of patients achieving rescue-free laxation (RFL), time to RFL, weekly laxations within 24 hours after dosing, rescue laxative use, and pain scores. Adverse events were monitored for safety. After pooling, 178 patients received methylnaltrexone (n = 116 with cancer) and 185 received placebo (n = 114 with cancer). Median baseline daily opioid morphine equivalents (mg/d) were higher in cancer (methylnaltrexone: 180; placebo: 188) versus noncancer patients (methylnaltrexone: 120; placebo: 80). The proportions of patients achieving RFL within 4 hours after ≥2 of the first 4 doses were significantly greater with methylnaltrexone (cancer: 56.9%; noncancer: 58.1%) versus placebo (cancer: 5.3%; noncancer: 11.3%; Methylnaltrexone reduced RFL time in advanced-illness patients with and without active cancer, while maintaining pain control with opioid treatment despite higher baseline opioid use among cancer patients.

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© 2021 Chamberlain et al.

Déclaration de conflit d'intérêts

Dr. Chamberlain has nothing to disclose. Dr. Israel is an employee of Bausch Health US, LLC, which has a proprietary interest in methylnaltrexone. Dr. Rhiner has received a grant from Wyeth Pharmaceuticals for the 302 study mentioned in this manuscript and was reimbursed by Salix Pharmaceuticals for travel expenses related to poster presentations at the 2018 World Congress on Regional Anesthesia & Pain Medicine and the 2018 Palliative and Supportive Care in Oncology meeting. Dr. Slatkin is an employee of Salix Pharmaceuticals since July 2016, has received personal fees from Salix Pharmaceuticals for consulting/speaking between 2012 and 2016, and has received a grant from Progenics Pharmaceuticals for the 302 study mentioned in this manuscript. Dr. Stambler is an employee of Progenics Pharmaceuticals, Inc., a subsidiary of Lantheus Holdings Inc., New York, NY. The authors report no other conflicts of interest in this work.