Difelikefalin in Chinese patients with chronic kidney disease-associated pruritus

Abstract Background Chronic kidney disease-associated pruritus (CKD-aP) is a common and debilitating condition in patients receiving in-centre haemodialysis. This study evaluated the efficacy and safety of difelikefalin (a new, intravenous treatment for moderate-to-severe CKD-aP approved in more than 40 countries) in a Chinese population receiving haemodialysis. Methods This Phase 3, multicentre, randomised placebo-controlled study included a 12-week double-blind treatment period, during which patients received either difelikefalin or placebo, followed by an optional 14-week open-label extension, in which all patients received difelikefalin. Endpoints included change from baseline in the Worst Itching Intensity Numerical Rating Scale (WI-NRS) at Week 4 (primary endpoint), the percentage of patients achieving a clinically relevant ≥ 3-point change in WI-NRS, patient-reported health-related quality-of-life measures, and incidence of adverse events. Results Difelikefalin-treated patients showed significantly greater improvements in least squares mean change from baseline in WI-NRS at Week 4 of the double-blind period compared with placebo (difelikefalin minus placebo: −0.81 [95% confidence interval: −1.25, −0.37]; P = 0.0003), and patients with ≥ 3-point improvement in WI-NRS at Week 12 (48.7% versus 33.8%, nominal P = 0.0235). Difelikefalin also improved health-related quality of life, with clinically relevant changes observed in 5-D itch and Skindex-10 in most patients at Week 4 of the open-label extension (estimated ≥ 62% and ≥ 56%, respectively). Adverse events were mostly mild or moderate in severity and generally consistent with the known safety profile of difelikefalin. Conclusion Difelikefalin effectively reduced pruritus intensity and improved quality of life in Chinese patients with CKD-aP receiving haemodialysis, supporting its use in this population.