Pooled Data on Studies of Difelikefalin for CKD-Associated Pruritus

ANNA 2021 National Symposium

Patients undergoing hemodialysis commonly develop chronic kidney disease-associated pruritus (CKD-aP), creating a negative impact on quality of life. Difelikefalin is a selective kappa opioid receptor agonist in development for the treatment of CKD-aP. In a phase 3 study in the United States, difelikefalin significantly reduced itch intensity based on the Worst Itching Intensity Numerical Rating Scale (WI-NRS) and was generally well tolerated in a cohort of patients with moderate-to-severe CKD-aP on hemodialysis in the United States (KALM-1). Results of global phase 3 studies (KALM-2) were similar.

Molly Cahill, MSN, RN, ANP-C, CNN, and colleagues reported itch-related quality of life outcomes in a pooled analysis of results of KALM-1 and KALM-2 during a virtual poster session at the ANNA 2021 National Symposium. The poster was titled Improvements in Itch-Related Quality of Life with Difelikefalin for Moderate-to-Severe Chronic Kidney Disease-Associated Pruritus: Pooled Analysis of KALM-1 and KALM-2 Phase 3 Studies in Hemodialysis Patients.

Patients were randomized to intravenous difelikefalin 0.5 mcg/kg or placebo three times per week for 12 weeks. Multi-dimensional itch-related questionnaires (5-D itch and Skindex-10 scales) were used to assess quality of life. The pooled data were analyzed based on mixed model for repeated measures.

The pooled studies included 851 patients; 426 were in the difelikefalin group and 425 in the placebo group. Mean baseline WI-NRS scores were 7.2 (1.4; difelikefalin) and 7.2 (1.5; placebo), confirming moderate-to-severe itch. In both studies, the primary endpoint of ≥3-point reduction in WI-NRS score at 12 weeks was met. Estimates for the pooled population were 51.1% with difelikefalin versus 35.2% with placebo (P<.001). Compared with placebo, difelikefalin showed overall greater and clinically meaningful improvements in 5-D itch and Skindex-10 total scores. Improvements in most of the domains on the two tests were greater with difelikefalin than with placebo.

In conclusion, the authors said, “Difelikefalin administered for 12 weeks to patients with moderate-to-severe CKD-aP undergoing hemodialysis resulted in significant relief of their itching accompanied by meaningful improvements in itch-related quality of life.”

Source: Cahill M, Fishbane S, Wooldridge T, Wen W, Munera C, Menzaghi F. Improvements in itch-related quality of life with difelikefalin for moderate-to-severe chronic kidney disease-associated pruritus: Pooled results of KALM-1 and KALM-2 phase 3 studies in hemodialysis patients. Abstract of a poster presented at the virtual 2021 American Nephrology Nurses Association National Symposium, May 2-5, 2021.