MedicalResearch.com Interview with:
William D. Chey, MD, AGAF, FACG, FACP, RFF
Professor of Medicine
Director, GI Physiology Laboratory
Co-director, Michigan Bowel Control Program
University of Michigan Health System
MedicalResearch: What are the main findings of the study?
Dr. Chey: Opiate analgesics are the most commonly prescribed medications in the US. GI side effects are common in patients who opiates. Constipation is the most common and most bothersome GI side effect of opiates. Peripherally acting mu opioid antagonists have been shown to benefit a subset of patients with opiate induced constipation. In 2 large, randomized, placebo controlled phase III trials, the peripherally acting, mu-opioid antagonist naloxegol was found to improve constipation in patients taking opioid analgesics for noncancer pain. Response rates were significantly higher with 25 mg of naloxegol than with placebo (intention-to-treat population: study 04, 44.4% vs. 29.4%, P = 0.001; study 05, 39.7% vs. 29.3%, P = 0.02) in both studies. Benefits were seen with the lower 12.5 mg dose in one of the studies (intention-to-treat population, 40.8% vs. 29.4%, P = 0.02). An interesting aspect of this study was the a priori inclusion of patients who had tried and failed to respond to other laxatives prior to enrollment. Response rates in this population were similar to the overall population (patients with an inadequate response to laxatives: study 04, 48.7% vs. 28.8%, P = 0.002; study 05, 46.8% vs. 31.4%, P = 0.01). Pain scores and daily opioid dosing were similar among the three groups before and after treatment.
MedicalResearch: Were any of the findings unexpected?
Dr. Chey: The lower dose of naloxegol was found to be more effective than placebo in only one of the phase III studies. The reasons for this finding are unclear though a dose response was observed for many of the pre-specified outcomes in both studies.
MedicalResearch: What should clinicians and patients take away from your report?
Dr. Chey: Naloxegol may provide an oral treatment option for patients with opiate induced constipation. An NDA has been filed with FDA.
MedicalResearch: What recommendations do you have for future research as a result of this study?
Dr. Chey: Comparative effectiveness studies between naloxegol and conventional laxative therapies for OIC would be of interest as would studies to evaluate the efficacy of PAMORAs for upper GI side effects of opiates.