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Neel Mehta,1,* Neal E Slatkin,2,3,* Robert J Israel,4,* Nancy Stambler,5,* Eric D Shah6,* 1Department of Anesthesiology, Weill Cornell School of Medicine, New York, NY, USA; 2School of Medicine, University of California Riverside, Riverside, CA, USA; 3Medical Affairs, Salix Pharmaceuticals, Bridgewater, NJ, USA; 4Clinical and Medical Affairs, Bausch Health US LLC, Bridgewater, NJ, USA; 5Clinical Research, Progenics Pharmaceuticals, a Subsidiary of Lantheus Holdings Inc, North Billerica, MA, USA; 6Division of Gastroenterology and Hepatology, University of Michigan, Michigan Medicine, Ann Arbor, MI, USA*These authors contributed equally to this workCorrespondence: Eric D Shah, Division of Gastroenterology and Hepatology, University of Michigan | Michigan Medicine, 300 N Ingalls Street, Ann Arbor, MI, 48109, USA, Tel +1 877 285-7788, Email ershah@umich.eduPurpose: We evaluated the impact of baseline patient characteristics on safety and efficacy of methylnaltrexone, a peripherally acting μ-opioid receptor antagonist, in patients with advanced illness with opioid-induced constipation (OIC).Patients and Methods: This analysis pooled data from 2 randomized, double-blind, placebo-controlled studies (study 302: NCT00402038; study 4000: NCT00672477) in patients with advanced illness, including cancer, and OIC. Patients were randomized to receive subcutaneous methylnaltrexone (study 302: 0.15 mg/kg; study 4000: 8 or 12 mg based on weight) or placebo every other day for 2 weeks. The proportions of patients achieving rescue-free laxation within 4 or 24 hours after the first dose of study drug were assessed in patient subgroups stratified by baseline age, Eastern Cooperative Oncology Group (ECOG) performance status, cancer status, laxative type, and opioid requirement. Treatment-emergent adverse events (TEAEs) were evaluated.Results: Overall, 363 patients were included in this analysis (methylnaltrexone, 178; placebo, 185). Mean (SD) age was 66.3 (13.7) years and 48.5% were men overall. A significantly greater proportion of patients receiving methylnaltrexone versus placebo achieved rescue-free laxation within 4 hours (111/178 [62.4%] vs 31/185 [16.8%]; P< 0.0001) and 24 hours (135/178 [75.8%] vs 81/185 [43.8%]; P< 0.0001) of the first dose. These trends were consistent across all subgroups. Most patients experienced ≥ 1 TEAE in the overall population (methylnaltrexone, 82.1%; placebo, 76.2%), which remained consistent when stratified by baseline characteristics. More than half of TEAEs were gastrointestinal in nature. Abdominal pain was more common in patients receiving methylnaltrexone than placebo across baseline characteristic subgroups.Conclusion: Methylnaltrexone treatment was superior to placebo in achieving rescue-free laxation within 4 and 24 hours after the first dose, irrespective of patients’ cancer status, baseline ECOG performance status, or baseline opioid or laxative use. The methylnaltrexone safety profile remained consistent across baseline characteristic subgroups.Keywords: methylnaltrexone, opioid-induced constipation, μ-opioid receptor antagonist |
