Effect of Methylnaltrexone SC on Constipation Symptoms Using the Patient Assessment of Constipation Symptoms (PAC-SYM) Questionnaire in Patients with Chronic Non-Malignant Pain and Opioid-Induced Constipation

Abstract

Purpose: To assess the effect of methylnaltrexone SC on patient-reported constipation symptoms. Methods: In this study, 469 subjects were randomized to either methylnaltrexone SC QD (daily) or QOD (every other day) dosing or placebo for 4 weeks and 460 received at least 1 dose. Subjects were eligible if they had an opioid dose of ≥50 mg oral morphine equivalents/day for ≥2 weeks and <3 rescue-free bowel movements (RFBMs)/week. Rescue laxative use was standardized and allowed if needed. Constipation symptoms were assessed using the Patient Assessment of Constipation-Symptoms (PAC-SYM) questionnaire at day 14 and day 28. PAC-SYM is a validated 12-item questionnaire assessing rectal (4 items), stool (4 items) and abdominal symptoms (4 items) on a 5-point likert scale ranging from 0 (none) to 4 (very severe). Symptom scores were calculated as the average of the individual items of the sub-scales. The global score was calculated as the mean of 12 items. Higher scores indicate higher symptom severity. Change from baseline in mean symptom and global scores were compared between the methylnaltrexone and placebo arms at day 28 using analysis of covariance, with treatment group as a factor and baseline score as covariate. Results: Majority of the patients in the study were female (60%), Caucasian (90%), average age was 49 years and back pain (60%) was the most frequently reported pain condition. The mean daily baseline morphine equivalent opioid dose was 222 mgs. At the end of the double-blind period (day 28), a statistically significant improvement was detected in the methylnaltrexone SC QD dosing group compared to placebo for rectal symptoms (-0.56 vs. -0.30; p<0.05), stool symptoms (-0.76 vs. -0.43; p<0.001) and the global PAC-SYM (-0.62 vs. -0.37; p<0.001) scores. For QOD dosing, improvement in stool symptoms (-0.69 vs.-0.43; p<0.05) and the global PAC-SYM scores (-0.52 vs. -0.37; p<0.05) were significantly greater in the methylnaltrexone group compared to the placebo group. No statistically significant differences were found in change from baseline in abdominal symptoms scores between either the methylnaltrexone SC QD or QOD dosing arms and placebo. Conclusion: Methylnaltrexone SC showed a significant improvement in patient reported constipation symptoms compared to placebo in patients with chronic non-malignant pain and opioid induced constipation. Disclosure: All authors are employees of Wyeth Research-manufacturer of Methylnaltrexone SC.