Difelikefalin Improved Quality of Life

Washington, DC—More than 40% of patients with chronic kidney disease (CKD) undergoing hemodialysis have moderate-to-severe pruritis, resulting in poor quality of life. Difelikefalin DFK;CR845), a selective kappa opioid receptor agonist that acts peripherally with a dual anti-inflammatory/antipruritic effect, has negligible abuse potential to date. Results of a previous phase 2 study of patients on hemodialysis with CKD-associated pruritis demonstrated a significant reduction in itch intensity in patients treated with difelikefalin. There was a correlation between itch reduction, assessed using the Worst Itching Intensity Numerical Rating Scale (WI-NRS) score, and significant improvement in itch-related quality of life measures.

Improvements in quality of life were measured by the Skindexc-10 and 5-D Itch scales. During a poster session at Kidney Week 2019, Steven Fishbane, MD, and colleagues reported results using the 5-D Itch scale domains to further characterize the impact of itch reduction on patient quality of life. The poster was titled Difelikefalin Improved Quality of Life (5-D Itch Scale-Domains) in Hemodialysis Patients with Pruritis in an 8-Week Phase 2 Randomized, Placebo-Controlled Study.

Patients were randomized to 1:1:1:1 to receive an intravenous bolus of DKF 1.5, 1.0, 0.5 mcg/kg or placebo at the end of each dialysis session over an 8-week treatment period. The 5-D Itch scale uses the domains of Degree, Duration, Direction (change over time of itch), Disability (sleep, leisure/social, housework/errands, work/school), and Distribution (body location of itch), each ranked on a 5-point increasing scale of severity, to measure the impact of itch reduction on patient quality of life. The focus of the current analysis was the 0.5 mcg/kg dosage that was advanced into phase 3 studies.

At week 8, patients in the DFK 0.5 mcg/kg arm (n=44) demonstrated a clinically meaningful improvement in 5-D Itch total scores compared with patients in the placebo arm: –5.7 vs –2.8 least squares mean (P<.001 vs placebo). There was a significant correlation between WI-NRS and 5-D total scores.

With the exception of Distribution (–0.6 vs –0.4; P=.368), at the end of week 8, significant improvement from baseline was reported across all subdomains in DFK versus placebo arms: Degree, –1.1 vs –0.5, P<.001 vs placebo; Duration, –1.2 vs –0.6, P=.003; Direction, –1.6 vs –0.7, P<.001; and Disability, –1.2 vs –0.5; P=.004.

The researchers said, “This analysis further characterized the impact of itch severity reduction with DFK indicating significant improvement in quality of life as measured by the 5-D Itch multidimensional questionnaire. Results demonstrate itch intensity reduction with DFK is associated with improved quality of life.”

Source: Fishbane S, Spencere RH, Munera C, Menzaghi F. Difelikefalin improved quality of life (5-D Itch scale domains) in hemodialysis patients with pruritis in an 8-week phase 2, randomized, placebo-controlled study. Abstract of a poster presented at the American Society of Nephrology Kidney Week 2019 (Abstract TH-PO245), November 7, 2019, Washington, DC.