Difelikefalin for CKD-aP: real world evidence of efficacy and safety in Italian patients

Background: Chronic kidney disease-associated pruritus (CKD-aP), defined as moderate to severe itching directly related to kidney disease, affects about one-third of haemodialysis patients and has been associated with poor quality of life, poor sleep, depression and increased mortality. Difelikefalin (DFK) is the first-in-class therapy approved by Food and Drug Administration and European Medicines Agency for this condition. The aim of the present study was to evaluate DFK efficacy and safety in a real-world setting in Italy. Methods: We retrospectively collected data for 20 patients treated with DFK in a compassionate manner, before the drug was commercialized, after obtaining approval by the relevant Ethics Committee for each individual case. Mean age and dialysis vintage were 72 ± 11 years and 54 ± 44 months, respectively; basal WI-NRS (24-h Worst Itching Intensity Numerical Rating Scale) score was 8.2 and 5D-ITCH was 18.6. Scratching lesions were detected in 15/20 patients. DFK was administered intravenously with weight-based dosing at the end of each dialysis session. Results: Eighteen of 20 patients were treated for 12 weeks; 2 patients stopped treatment for dizziness (n = 1) and discomfort (n = 1). WI-NRS score improved >3 in 11/18 (61%) at Week 4 and in 16/18 (88%) at Week 12. 5D-ITCH decreased from basal 18.6 to 10.5 at Week 12, while sleep quality at the same time points changed from 2.6 to 5.8; scratching lesions disappeared in 12/15 (80%). Except for the two early therapy breaks, no other side effects were reported. Conclusions: In haemodialysis patients affected by CKD-aP, DFK is an effective and safe treatment that might clearly improve this distressing and overlooked condition.