RELATIONSHIP BETWEEN ITCH INTENSITY AND PATIENT-REPORTED DISEASE IMPROVEMENT IN PATIENTS WITH CHRONIC KIDNEY DISEASE-ASSOCIATED PRURITUS TREATED WITH DIFELIKEFALIN

Abstract BACKGROUND AND AIMS Chronic kidney disease-associated pruritus (CKD-aP) is a common condition in patients with CKD undergoing haemodialysis (HD), leading to poor sleep quality, reduced quality of life and depression. Difelikefalin is a selective kappa opioid receptor agonist approved in the United States for the treatment of moderate-to-severe pruritus in adults undergoing HD, which significantly reduced itch intensity in HD patients with CKD-aP in the Phase 3 KALM-1 and KALM-2 multicentre, placebo-controlled trials. The KALM trials used the Worst-Itching Numerical Rating Scale (WI-NRS) to assess itch-intensity [range from 0 (no itching) to 10 (worst itching imaginable)] and the Patient Global Impression of Change (PGIC) to assess the patient's overall perception of change in itch (range from ‘very much improved’ to ‘very much worse’) relative to the start of the study. The aim of this post hoc analysis was to establish how the WI-NRS score relates to the PGIC and to assess a clinically relevant change in WI-NRS. METHOD A post hoc analysis of data from KALM-1 and KALM-2 was performed. Studies enrolled maintenance HD patients with mean baseline 24-h WI-NRS score > 4 in KALM-1 or ≥ 5 in KALM-2. Patients were randomized 1:1 to intravenous difelikefalin 0.5 mcg/kg or placebo three times/week for 12 weeks. Patients completed the PGIC at the end of the 12-week, double-blind treatment period, as well as completing the WI-NRS daily. Cumulative distribution function (CDF) analyses were performed at Week 12. Results are reported for 50% CDF at week 12. RESULTS For the overall population, ‘very much improved’ corresponded to a 5-to-6-point WI-NRS reduction; ‘much improved’ corresponded to a 3-to-4-point WI-NRS reduction; and ‘minimally improved’ corresponded to a 1-to-2-point WI-NRS reduction (Figure 1). CONCLUSION There is a clear relationship between the PGIC and the WI-NRS, with greater reductions in itch severity corresponding to perceptions of better overall improvement in itch following treatment with difelikefalin. A 3-point reduction in WI-NRS can be considered clinically relevant, since it was perceived by patients as equivalent to their itch being ‘much improved’. This analysis further corroborates similar clinically meaningful changes in pruritus, previously reported in patients with CKD-aP, as ≥ 3-points [1, 2].