Efficacy of Difelikefalin for the Treatment of Moderate to Severe Pruritus in Hemodialysis Patients: Pooled Analysis of KALM-1 and KALM-2 Phase 3 Studies.
Rationale & Objective: Chronic kidney disease-associated pruritus (CKD-aP) in patients treated by hemodialysis (HD) impairs quality of life (QoL). Difelikefalin, a selective κ-opioid receptor agonist, decreased the intensity of CKD-aP in patients undergoing HD. This pooled analysis evaluated difelikefalin's efficacy and the itch-related QoL overall and in subgroups defined by demographics or disease characteristics.
Study Design: In KALM-1 and KALM-2, participants were randomized (1:1) to receive intravenous difelikefalin or placebo 3 times/wk for 12 weeks, followed by a 52-week open-label extension.
Setting & Participants: Adults with moderate to severe CKD-aP treated by HD in North America, Europe, and the Asia-Pacific region.
Intervention: Intravenous difelikefalin at 0.5 mcg/kg or placebo.
Outcomes: Itch intensity (Worst Itching Intensity Numerical Rating Scale [WI-NRS]) and itch-related QoL (Skindex-10 and 5-D Itch questionnaires).
Results: 851 participants were randomized (difelikefalin, n = 426; placebo, n = 425). This pooled analysis demonstrated early (week 1), sustained difelikefalin efficacy, with significantly greater achievement of ≥3-point WI-NRS reduction with difelikefalin (51.1%) versus placebo (35.2%;
Limitations: Subgroup samples were small. The WI-NRS, Skindex-10, and 5-D Itch are not used in routine clinical care of dialysis patients; therefore, findings may not reflect the real-world effectiveness of difelikefalin.
Conclusions: Difelikefalin demonstrated rapid, sustained efficacy, with consistent results in diverse populations of patients treated by HD.
Funding: Cara Therapeutics, Inc.
Trial Registration: The KALM-1 trial is registered as NCT03422653 and the KALM-2 trial is registered as NCT03636269.
Topf J, Wooldridge T, McCafferty K, Schömig M, Csiky B, Zwiech R, et al. Efficacy of difelikefalin for the treatment of moderate to severe pruritus in hemodialysis patients: pooled analysis of KALM-1 and KALM-2 phase 3 studies. Kidney Med. 2022 Jun 28;4(8):100512. doi: 10.1016/j.xkme.2022.100512. PMID: 36016762.