Real-world safety of difelikefalin for chronic kidney disease-associated pruritus: initial insights from a European managed access programme.

Background: Chronic kidney disease-associated pruritus (CKD-aP) is a debilitating condition with limited treatment options. A managed access programme (MAP) began in October 2021 to provide early, controlled access to the novel antipruritic difelikefalin to European and Australian patients with CKD-aP with no local access to commercially available treatments. Here, we describe the safety data collected up to 31 October 2024. Methods: Eligible adults with moderate-to-severe CKD-aP receiving in-centre haemodialysis (HD) were provided with difelikefalin (0.5 µg/kg) intravenously after each HD session. All adverse events (AEs) were recorded; a Global Drug Safety team assessed seriousness and causality. AE details, including outcomes, were also recorded. Results: A total of 438 patients were provided with a median of 115 (min-max: 30-1035) days of difelikefalin treatment. Of these, 167 (38.1%) patients experienced 458 AEs. Of 246 serious AEs (SAEs), 10.2% were considered possibly related to difelikefalin. Of those with a known outcome, 88.0% were resolved during the MAP. There were 63 fatal SAEs, none considered related to difelikefalin. There were 152 non-serious AEs, of which 63.8% were deemed possibly/probably related to difelikefalin. Of the 59 difelikefalin-related non-serious AEs with a known outcome, 86.4% were resolved during the MAP. Most AEs and SAEs were consistent with conditions typical of patients with CKD requiring HD and/or the known safety profile of difelikefalin. Conclusions: No new safety signals were detected in this MAP analysis over a 3-year period. The overall safety results were consistent with the known safety profile for difelikefalin patients with moderate-to-severe CKD-aP receiving HD.