Influence of Concomitant Opioids on Difelikefalin Treatment Outcomes in Adults with Moderate-to-Severe Pruritus on Maintenance Hemodialysis: Exploratory Analyses.

IF 2.1 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Kidney & blood pressure research Pub Date : 2026-01-01 Epub Date: 2025-12-17 DOI:10.1159/000549648

James O Burton, Satkiran Grewal, Thilo Schaufler, Despina Ruessmann, Murray Lowe, Warren Wen, Steven Fishbane

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引用次数: 0

Abstract

Introduction: Difelikefalin (DFK) is approved to treat chronic kidney disease-associated pruritus (CKD-aP) in adults undergoing maintenance hemodialysis. The influence of concomitant opioid use on DFK treatment outcomes remains uncertain.

Methods: Exploratory analyses were conducted from the phase 3, placebo (PBO)-controlled KALM-1 and KALM-2 trials (datasets pooled), and the phase 3, open-label, single-arm Study 3105. Each trial assessed the safety and efficacy of DFK 0.5 µg/kg in adults with moderate-to-severe CKD-aP. We report key endpoints from the primary studies, including reduction in itch intensity (Worst Itching Intensity Numerical Rating Scale [WI-NRS]), and improvements in itch-related quality of life (QoL; 5-D itch and Skindex-10), according to concomitant opioid use (+O or -O).

Results: In KALM-1/KALM-2, 24.2% of participants on DFK and 30.4% on PBO were taking concomitant opioids. Regardless of opioid use, a greater estimated percentage of those receiving DFK achieved ≥3- or ≥4-point clinically relevant reductions in itch intensity (WI-NRS; p < 0.05), or complete response (≥80% weekly mean WI-NRS scores of 0 or 1) by week 12, versus PBO. Greater improvements in itch-related QoL were also reached with DFK, versus PBO, irrespective of concomitant opioid use. With either treatment, nonfatal serious TEAEs were more common among concomitant opioid users (DFK+O: 44.7% vs. DFK-O: 19.0%; PBO+O: 38.0% vs. PBO-O: 15.9%), as were severe TEAEs. In Study 3105, 31% were taking concomitant opioids.

Conclusion: DFK reduced itch intensity and improved QoL, regardless of concomitant opioid use. Similar concomitant opioid-dependent safety findings were observed. With or without concomitant opioid use, DFK demonstrated considerable efficacy that improved QoL. Increased TEAEs with concomitant opioid use with either treatment suggests careful medication management is advisable.

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伴用阿片类药物对维持性血液透析中中度至重度瘙痒的成人异花镰刀素治疗结果的影响：探索性分析

Difelikefalin （DFK）被批准用于治疗维持性血液透析（HD）成人慢性肾脏疾病相关性瘙痒（CKD-aP）。同时使用阿片类药物对DFK治疗结果的影响仍不确定。方法：从3期安慰剂（PBO）对照的KALM - 1和KALM - 2试验（合并数据集）和3期开放标签单臂研究3105中进行探索性分析。每项试验都评估了DFK 0.5µg/kg对中重度CKD-aP成人患者的安全性和有效性。我们报告了主要研究的关键终点，包括瘙痒强度的降低（最差瘙痒强度数值评定量表[WI - NRS]），以及根据伴随使用阿片类药物（+O或-O）瘙痒相关生活质量（QoL； 5-D瘙痒和皮肤指数-10）的改善。结果：在KALM‑1/KALM‑2中，24.2%的DFK参与者和30.4%的PBO参与者同时服用阿片类药物。无论是否使用阿片类药物，接受DFK治疗的患者中，瘙痒强度临床相关降低≥3或≥4点的估计百分比（WI - NRS; p）更高。结论：无论是否同时使用阿片类药物，DFK均可降低瘙痒强度并改善生活质量。同时观察到类似的阿片类药物依赖性安全性结果。无论是否同时使用阿片类药物，DFK都显示出相当大的改善生活质量的功效。两种治疗同时使用阿片类药物会增加teae，建议谨慎用药。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Kidney & blood pressure research 医学-泌尿学与肾脏学

CiteScore

4.80

自引率

3.60%

发文量

审稿时长

6-12 weeks

期刊介绍： This journal comprises both clinical and basic studies at the interface of nephrology, hypertension and cardiovascular research. The topics to be covered include the structural organization and biochemistry of the normal and diseased kidney, the molecular biology of transporters, the physiology and pathophysiology of glomerular filtration and tubular transport, endothelial and vascular smooth muscle cell function and blood pressure control, as well as water, electrolyte and mineral metabolism. Also discussed are the (patho)physiology and (patho) biochemistry of renal hormones, the molecular biology, genetics and clinical course of renal disease and hypertension, the renal elimination, action and clinical use of drugs, as well as dialysis and transplantation. Featuring peer-reviewed original papers, editorials translating basic science into patient-oriented research and disease, in depth reviews, and regular special topic sections, ''Kidney & Blood Pressure Research'' is an important source of information for researchers in nephrology and cardiovascular medicine.