MO467: Time to Improvement of Itch Intensity in Patients With Chronic Kidney Disease-Associated Pruritus Treated With Difelikefalin

Abstract

Abstract BACKGROUND AND AIMS Chronic kidney disease-associated pruritus (CKD-aP) is frequently reported by patients with CKD undergoing haemodialysis (HD), impacting sleep quality, 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. In the Phase 3 KALM-1 and KALM-2 multicentre, placebo-controlled trials, difelikefalin significantly reduced itch intensity in HD patients with CKD-aP. 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)], for which a ≥ 3-point improvement has been validated as a clinically relevant reduction in itch in this patient population. The aim of this post hoc analysis was to determine the time to clinically relevant improvement in WI-NRS score in patients with CKD-aP treated with difelikefalin. METHOD The KALM-1 and KALM-2 studies enrolled maintenance HD patients with moderate-to-severe CKD-aP [mean baseline 24-h WI-NRS score > 4 (KALM-1) or ≥ 5 (KALM-2)]. Patients were randomized 1:1 to intravenous difelikefalin 0.5 mcg/kg or placebo 3 times/week for 12 weeks. Patients completed the WI-NRS questionnaire daily. A post hoc analysis was performed to assess the cumulative proportion of patients achieving a ≥ 3-point improvement in WI-NRS score each week. RESULTS Two-thirds of patients treated with difelikefalin who reported a response did so within 4 weeks. A further 4 weeks of treatment resulted in over 90% of difelikefalin responders reporting a clinically relevant improvement (Figure 1). Fewer patients receiving placebo reported a reduction in itch at any time during treatment (44% versus 57% of difelikefalin-treated patients) and any improvements in pruritus were reported later than for difelikefalin-treated patients. CONCLUSION A clinically relevant response to difelikefalin is likely to be reported by most patients within 4 weeks and almost all patients benefit from improvement after a further 4 weeks of treatment. Compared with patients receiving a placebo, those treated with difelikefalin are more likely to experience clinically-relevant reductions in itch, as well as an earlier improvement in pruritus.