Difelikefalin effective in treatment of pruritus for patients receiving hemodialysis: JAMA

Patients with pruritus receiving hemodialysis frequently experience oppressive physical and psychiatric symptoms that directly affect their quality of life and increase mortality. However, treatment options are limited.

A study was conducted to determine the clinically recommended dose of difelikefalin, a κ-opioid receptor agonist, based on the efficacy, dose-response, safety, and pharmacokinetics.

This randomized, double-blind, placebo-controlled, 4-arm phase 2 trial was conducted from February 1, 2019, to October 22, 2019, at 94 sites in Japan. Patients with moderate to severe pruritus receiving hemodialysis were enrolled. Difelikefalin (0.25, 0.5, and 1.0 μg/kg) and placebo were intravenously administered 3 times a week at the end of each hemodialysis session for 8 weeks. The primary endpoint was the change from baseline in the weekly mean Worst Itching Intensity Numerical Rating Scale (NRS) score at week 8. Secondary outcomes measured changes in the itch-related quality-of-life score using the Skindex-16 and 5-D itch scale. Safety was assessed according to adverse events, laboratory tests, vital signs, body weight, and a 12-lead electrocardiogram.

Results:

• A total of 247 Japanese patients were randomized to placebo (n = 63), 0.25 μg/kg of difelikefalin (n = 61), 0.5 μg/kg of difelikefalin (n = 61), or 1.0 μg/kg of difelikefalin (n = 62).
• The changes from baseline in the adjusted mean (SE) of the 24-hour Worst Itching Intensity NRS score at week 8 were −2.86 (0.29) in the placebo group, −2.97 (0.29) in the 0.25 μg/kg of difelikefalin group, −3.65 (0.30) in the 0.5 μg/kg of difelikefalin group, and −3.64 (0.30) in the 1.0 μg/kg of difelikefalin group.
• Significant differences were found in the 0.5 μg/kg of difelikefalin group (adjusted mean difference, −0.80; 95% CI, −1.55 to −0.04; P = .04) and the 1.0 μg/kg of difelikefalin group compared with placebo.
• The Skindex-16 overall score and 5-D itch scale total score indicated an improvement with treatment with 0.5 and 1.0 μg/kg of difelikefalin
• The incidence of adverse events was 67% (42 of 63 patients) in the placebo group, 72% (44 of 61 patients) in the 0.25 μg/kg of difelikefalin group, 77% (47 of 61 patients) in the 0.5 μg/kg of difelikefalin group, and 85% (53 of 62 patients) in the 1.0 μg/kg of difelikefalin group.
• No dependency was reported.

The findings of this phase 2 randomized clinical trial of difelikefalin suggest that 0.5 μg/kg of difelikefalin should be the clinically recommended dose as a new option for treating moderate to severe pruritus in patients undergoing hemodialysis because of its efficacy, acceptable tolerability, and manageable safety profile.

Reference:

Efficacy and Safety of Difelikefalin in Japanese Patients With Moderate to Severe Pruritus Receiving Hemodialysis: A Randomized Clinical Trial by Ichiei Narita, et al. published in the JAMA Netw Open.

doi:10.1001/jamanetworkopen.2022.10339