Poster Number-73 - Impact of Patient Subgroups on the Efficacy of Methylnaltrexone for Opioid-Induced Constipation in Patients With Advanced Illness

Impact of Patient Subgroups on the Efficacy of Methylnaltrexone for Opioid-induced Constipation in Patients With Advanced Illness

Purpose:

Constipation is a leading adverse event of opioid use and is associated with reduced quality of life and lowered adherence to opioid treatment. Methylnaltrexone (MNTX) is a peripherally acting µ-opioid receptor antagonist indicated for opioid-induced constipation (OIC) in patients with advanced illness who are receiving palliative care and in patients with chronic noncancer pain.¹ MNTX relieves constipation without diminishing the effects of opioid analgesia. We investigated whether baseline patient characteristics, including age, Eastern Cooperative Oncology Group (ECOG) performance status, cancer status, and oral morphine equivalent dose, impact the efficacy of MNTX in patients with advanced illness and OIC.

Methods:

This post hoc analysis included pooled data from 2 randomized, double-blind, placebo (PBO)-controlled studies (study 302 [NCT00402038]² and study 4000 [NCT00672477]³) involving patients with advanced illness, including cancer. Study 302 included 133 patients with advanced illness randomized to receive subcutaneous (SC) MNTX 0.15 mg/kg or PBO every other day (QOD) for 2 weeks, with possible dose escalation to 0.30 mg/kg in the second week.² Study 4000 included 230 patients with advanced illness receiving SC MNTX 8 mg or 12 mg QOD in patients weighing 38 kg to < 62 kg or ≥ 62 kg, respectively, or PBO for 2 weeks.³ The proportion of patients who achieved a rescue-free laxation (RFL) within 4 hours after the first dose of study drug was assessed in patient subgroups stratified by baseline age (< 65 vs ≥ 65), performance status (ECOG ≤ 2 vs ECOG > 2), cancer status, and oral morphine equivalent dose (< 80 mg/day, 80 to < 150 mg/day, and ≥ 150 mg/day). Institutional review board approval was obtained for these studies.

Results:

Overall, 363 patients were included in the pooled analysis (MNTX = 178; PBO = 185). Mean age was 67.8 years in the MNTX group and 66.7 years in the PBO group; 46.8% were men across all treatment groups. Overall, a significantly greater proportion of patients receiving MNTX achieved RFL within 4 hours (n = 111/178 [62.4%] vs n = 31/185 [16.8%], P < 0.0001). When stratified by baseline characteristics, a significantly greater proportion of patients in the MNTX group (P < 0.0001 for all comparisons MNTX vs PBO) achieved RFL within 4 hours after the first dose versus PBO, regardless of baseline age (< 65 years: 63.9% vs 14.6%; ≥ 65 years: 61.1% vs 18.8%), performance status (ECOG ≤ 2: 66.7% vs 22.5%; ECOG > 2: 59.0% vs 12.4%), cancer status (cancer: 63.8% vs 14.9%; no-cancer: 59.7% vs 19.7%), and oral morphine equivalent dose (< 80 mg: 57.1% vs 12.3%; 80 to < 150 mg: 61.5% vs 19.0%; ≥ 150 mg: 64.9% vs 18.6%). Most adverse events associated with MNTX were gastrointestinal in nature and included abdominal pain and nausea.

Conclusion:

Across the range of patient characteristics, including age, ECOG performance status, cancer status, and oral morphine equivalent dose, treatment with MNTX was superior to PBO in achieving RFL within 4 hours after the first dose.

References: 1. Relistor [package insert]. Bridgewater, NJ: Salix Pharmaceuticals, Inc. 2020.
2. Thomas J, Karver S, Cooney GA, et al. Methylnaltrexone for opioid-induced constipation in advanced illness. N Engl J Med. 2008;358(22):2332–2343.
3. Bull J, Wellman CV, Israel RJ, et al. Fixed-dose subcutaneous methylnaltrexone in patients with advanced illness and opioid-induced constipation: results of a randomized, placebo-controlled study and open-label extension. J Palliat Med. 2015;18(7):593–600.