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Bruce H Chamberlain,1 Michelle Rhiner,2 Neal E Slatkin,3,4 Nancy Stambler,5 Robert J Israel6 1Genesis Healthcare, Davenport, IA, USA; 2Loma Linda University Health, Department of Family Medicine, Loma Linda, CA, USA; 3University of California Riverside, School of Medicine, Riverside, CA, USA; 4Salix Pharmaceuticals, Medical Affairs, Bridgewater, NJ, USA; 5Progenics Pharmaceuticals, Inc., a subsidiary of Lantheus Holdings Inc., Clinical Research, New York, NY, USA; 6Bausch Health US, LLC, Clinical and Medical Affairs, Bridgewater, NJ, USACorrespondence: Robert J IsraelBausch Health US, LLC, Clinical and Medical Affairs, 400 Somerset Corporate Boulevard, Room 6-1001, Bridgewater, NJ, 08807, USATel +1 908 541-2288Fax +1 585 338-0668Email Robert.Israel@bauschhealth.comPurpose: 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.Patients and Methods: 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.Results: 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%; P < 0.0001). The median time to laxation within 24 hours after the first methylnaltrexone dose was significantly shorter in cancer and noncancer patients versus placebo (cancer: 0.96 vs 22.53 hours, P < 0.0001; noncancer: 1.25 vs > 24 hours, P = 0.0002). The mean number of weekly laxations within 24 hours after dosing by week 2 was significantly higher in methylnaltrexone- vs placebo-treated cancer and noncancer patients (cancer: 7.9 vs 4.9, P < 0.0001; noncancer: 8.4 vs 5.0, P < 0.0001). Methylnaltrexone reduced rescue laxative use without impacting pain scores. Consistent with previous data, methylnaltrexone was well tolerated in cancer and noncancer patients, and the AE profile did not suggest symptoms of opioid withdrawal.Conclusion: 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.Keywords: methylnaltrexone, opioid-induced constipation, μ-opioid receptor antagonist, cancer, chronic pain |
