Equal preference for naloxegol or PEG 3350 for opioid-induced constipation

Last Updated: 2019-05-15

By Marilynn Larkin

NEW YORK (Reuters Health) - About half of patients with opioid-induced constipation (OIC) prefer prescription naloxegol and about half prefer over-the-counter polyethylene glycol (PEG) 3350, researchers have found.

"The study legitimizes past and current treatment algorithms recommending the use of over-the-counter treatments as first-line agents and also substantiates the use of peripherally-acting mu-opioid receptor antagonists (PAMORAs) like naloxegol in the treatment paradigm for OIC," Dr. Darren Brenner of Northwestern University Feinberg School of Medicine in Chicago told Reuters Health.

"Furthermore, this study validates the utilization of the bowel function index (BFI) not only as a clinical indicator for prescription treatment of OIC, but also as a measure of clinical response to therapy," he said by email. "We found that there was an almost dichotomous split in patient preferences for PEG 3350 or naloxegol, and in the majority of cases, this preference was strong and correlated highly with overall improvements in bowel parameters."

For the crossover study, Dr. Brenner and colleagues randomized 276 adults of various ages (about 65% women; about 80% white) with baseline BFI scores of at least 30 to one of two treatment sequences, separated by a one-week washout period: naloxegol/PEG 3350 or PEG 3350/naloxegol. Daily during the two-week treatment periods, patients either took a 25-mg naloxegol pill or 17 mg of PEG 3350 (the active ingredient in MiraLAX) dissolved in 4 to 8 ounces of liquid.

Most patients (94.1%) had musculoskeletal or connective tissue disorders.

As reported online May 3 in the American Journal of Gastroenterology, 246 patients (89%) completed both treatment periods and reported a preference. Similar proportions of patients reported overall preference for naloxegol (50.4%) or PEG 3350 (48%); 1.6% reported no preference.

Medication characteristics influencing preference were similar for both treatments, except more patients who preferred naloxegol cited "convenience" and "working quickly" as strong influences of preference (69.9% and 39%, respectively) compared to patients who preferred PEG 3350 (29.9% and 27.4%, respectively).

Patients under age 50 or those receiving laxatives within the previous two weeks generally preferred naloxegol.

Changes from baseline in overall BFI and Patient Global Impression of Change scores were similar between treatments, but analyses according to treatment preference showed that clinical improvement aligned with reported preference.

Specifically, among patients preferring naloxegol, the mean BFI score reduction after two weeks of naloxegol treatment (-33.5) was nearly twice the mean reduction seen after PEG 3350 (-17.6). Similarly, among patients preferring PEG 3350, the mean BFI score reduction at two weeks was -34.1 after PEG 3350 versus -14.5 after naloxegol.

"Almost equal proportions of patients with OIC reported similar preference for daily naloxegol or PEG 3350 treatment, and their preference was generally supported by clinically relevant and measurable improvements in OIC symptoms," the authors conclude.

Dr. Anton Bilchik, chief of gastrointestinal research at John Wayne Cancer Institute at Providence Saint John's Health Center in Santa Monica, California, told Reuters Health, "Although this is an important study...we have not found that the benefits of OTC PEG 3350 and naloxegol are age-dependent. OTC PEG 3350 is typically given as a first-line treatment for OIC and naloxegol if the treatment is ineffective."

"Although both treatments are safe, there are more side effects with naloxegol mainly related to abdominal pain and bloating," he said by email. "The cost is significantly higher for naloxegol."

"Opioid induced constipation is common and very challenging to treat," he noted. "Until recently, laxatives were the only option and after a while patients often stop responding to laxatives. Naloxegol offers an effective alternative treatment and specifically targets the opioid receptor. It is likely that many more drugs targeting these pathways will be available soon."

"Reducing the use of opioids, given the addiction crisis and side effects, is an imperative," he added. "Many non-opioid medications are now available to help manage chronic pain. Physicians should try to prevent opioid use at all costs."

The study was funded by Astra Zeneca. Dr. Brenner has served as a speaker/advisor for the company, three coauthors are employees, another coauthor received a research grant from the company.

SOURCE: http://bit.ly/2VFw8ic

Am J Gastroenterol 2019.