Effect of subcutaneous methylnaltrexone on patient-reported outcomes in advanced illness patients with opioid-induced constipation

Opioid-induced constipation (OIC) is a common side effect of opioid therapy that can be more distressing to chronic pain patients than the underlying pain syndrome. Subcutaneous methylnaltrexone (MNTX) has demonstrated efficacy in increasing the frequency of rescue-free bowel movements (RFBMs) in advanced illness patients with OIC. Addressing more subjective, patient-reported outcomes (PROs) in OIC patients may lead to improved symptom control, quality of life, and satisfaction with therapy. The objective of this analysis was to examine the impact of MNTX on PROs of constipation distress, BM difficulty, and Global Clinical Impression of Change (GCIC), all pre-specified secondary efficacy assessments in a 2-week, randomized, double-blind, placebo (PBO)-controlled trial. Advanced illness patients (n=133) maintained on stable doses of opioids, and who had failed prior laxative therapy, were treated every other day with MNTX 0.15 mg/kg or PBO. Demographic and baseline characteristics were similar between groups. At baseline, 60% and 63% of patients in the PBO and MNTX groups reported “quite a bit” or “very much” constipation-related distress. On Day 1 of treatment, 52.7% of MNTX treated patients reported that constipation distress had “improved” vs. 29.7% of PBO-treated patients, a finding that persisted throughout the study. For doses of MNTX and PBO that resulted in a RFBM within 4 hours, the BM difficulty was rated as “moderate,” “considerable,” or “great” for 33.0% (58 of 176) of doses in the MNTX group vs. 50.0% (24 of 48) of doses in the PBO group. Regarding CGIC, 73.5% (Day 7) and 67.9% (Day 14) of MNTX-treated patients reported that bowel status was “Better,” vs. 35.1% and 44.6% of PBO-treated patients. These PRO findings complement objective assessments of MNTX-related improvements in bowel function, and indicate that MNTX decreases symptom severity across several dimensions in patients with advanced illness. Development of abstract supported by Salix Pharmaceuticals, Inc.