Difelikefalin in Black/African American Hemodialysis Patients with Moderate-to-Severe Pruritus: Post hoc Analysis of KALM-1 and KALM-2

Abstract

<b><i>Introduction:</i></b> Black and African American (AA) people are over-represented in the kidney failure population; therefore, the safety and efficacy of difelikefalin in Black/AA patients was evaluated. <b><i>Methods:</i></b> This was a post hoc, pooled exploratory subgroup analysis of the Phase 3 KALM-1 and -2 studies. Patients undergoing hemodialysis (HD) who had moderate-to-severe chronic kidney disease-associated pruritus (CKD-aP) at enrollment were stratified into self-reported Black/AA or White subgroups. Patients were randomized (1:1) to receive intravenous (IV) difelikefalin 0.5 µg/kg or placebo for 12 weeks. Difelikefalin efficacy was assessed with validated patient-reported outcome questionnaires: 24-h Worst Itch Numerical Rating Scale (WI-NRS), 5-D itch, and Skindex‑10. <b><i>Results:</i></b> There were 249 (29.3%) patients from the KALM studies that self-identified as Black/AA (<i>n</i> = 135 difelikefalin; <i>n</i> = 114 placebo). Clinically meaningful (≥3-point) reduction in WI-NRS score was achieved by 47.9% of Black/AA patients with difelikefalin versus 24.6% with placebo (<i>p</i> &lt; 0.001). More Black/AA patients achieved a ≥5-point 5-D itch total improvement (54.9% vs. 35.7%; <i>p</i> = 0.013) and a ≥15-point Skindex-10 score improvement with difelikefalin versus placebo (49.0% vs. 28.9%; <i>p</i> = 0.006) compared with White patients. Incidence of treatment-emergent adverse events (TEAEs) was higher for Black/AA patients (difelikefalin: 78.5%; placebo: 70.8%) versus White patients (difelikefalin: 64.8%; placebo: 61.8%). <b><i>Conclusion:</i></b> In this post hoc analysis, difelikefalin was efficacious in the Black/AA population and had an acceptable safety profile.