Patients With OIC Prefer Naloxegol, PEG 3350 Equally

Nicola M. Parry, DVM

May 14, 2019

For managing opioid-induced constipation (OIC) among individuals receiving treatment for noncancer pain, similar proportions of patients preferred naloxegol and the osmotic laxative polyethylene glycol (PEG) 3350, a recent head-to-head study published online May 3 in the American Journal of Gastroenterology has shown.

"[A]nd their preference was generally supported by clinically relevant and measurable improvements in OIC symptoms," write Darren M. Brenner, MD, Northwestern University-Feinberg School of Medicine, Chicago, Illinois, and colleagues.

OIC is a common side effect experienced by many patients receiving opioids for chronic pain.

For first-line treatment of OIC, consensus guidelines recommend over-the-counter (OTC) laxatives, of which PEG 3350 is commonly used. However, OIC does not reliably respond to treatment with conventional laxatives, possibly because they fail to target the underlying pathophysiology of the condition.

In contrast, naloxegol is a peripherally acting mu-opioid receptor antagonist that directly targets the opioid-related mechanism for inducing constipation. It is approved by the US Food and Drug Administration for treating OIC in adults with chronic noncancer pain.

However, studies on patient-reported outcomes associated with using different available treatments for OIC are lacking, especially those comparing use of prescription agents with OTC laxatives.

With this in mind, Brennan and colleagues conducted a randomized, open-label, phase 4 study to investigate preferences for naloxegol or PEG 3350 among patients with OIC associated with chronic noncancer pain.

The study used a 6-week crossover design and included two treatment sequence groups, with each sequence comprising 2-week daily treatment periods separated by a 1-week washout period.

The investigators included 246 adults ages 18 to 84 years at 53 US sites. To be eligible for inclusion, patients had to meet the Rome IV diagnostic criteria for OIC, be on stable doses of opioids for noncancer pain, and have a bowel function index (BFI) score of at least 30 at baseline.

The study's primary endpoint was patient preference for naloxegol or PEG 3350.

The study randomly assigned patients in a 1:1 ratio to the two treatment sequences, receiving naloxegol (one 25-mg tablet daily) first, followed by PEG 3350 (17 g dissolved in 4 to 8 oz liquid once daily); or PEG 3350 first, followed by naloxegol.

According to the investigators, 50.4% (124/246) of patients indicated a preference for naloxegol therapy, whereas 48% (118/246) preferred PEG 3350 (P = .92). And only 1.6% (4/246) of patients indicated no preference.

"Treatment sequence did not affect preference," the authors say.

Although most medication factors similarly affected preference for both treatments, convenience and working quickly were two characteristics reported as having strong influences on preference for more patients who preferred naloxegol (69.9% and 29%, respectively) than for those who preferred PEG 3350 (39.9% and 27.4%, respectively).

Subgroup analyses also showed that patients who were using laxatives within the 2 weeks before screening (56% vs 41.7%), and those who were younger than 50 years (53.4% vs 41.4%) also typically preferred naloxegol.

In contrast, patients aged 65 years or older preferred PEG 3350 (54.8% vs 42.9%).

The investigators also evaluated changes in BFI (as a marker of OIC symptoms) and Patient Global Impression of Change (PGIC; as a marker of general health) scores.

For both scores, changes from baseline were similar between the two treatments. However, when they analyzed the data according to patient preference, Brennan and colleagues found that clinical improvement among patients aligned with reported treatment preference.

This emphasizes the value of including patients' self-reported treatment experiences in treatment decision-making plans, they say.

"After only 2 weeks of daily treatment with these products, patients were able to report differences that were shown to correspond to the validated clinical evaluation tools of the BFI and PGIC."

The overall safety profiles observed in the treatment groups were consistent with the known safety profiles of naloxegol and PEG 3350.

The authors stress that this was the first randomized, multicenter, phase 4 study to use BFI as a screening baseline criterion and also to assess change with treatment.

"The incorporation of the BFI in this study allowed for a better understanding of the relationship between this clinical assessment of constipation and the patient experience of OIC," Brennan and colleagues conclude.

This study was supported by the AstraZeneca Pharmaceuticals LP. One author has reported serving as a speaker/advisor for AstraZeneca, Daiichi Sankyo, Salix, and Shionogi Pharmaceuticals. Three authors have reported being employees of AstraZeneca. One author has reported receiving a research grant from AstraZeneca for a study on the pharmacodynamics of naloxegol treatment.

Am J Gastroenterol. Published online May 3, 2019. Abstract

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