From the Kimberly and Eric J. Waldman Department of Dermatology (B.S.K., M.L.), the Mark Lebwohl Center for Neuroinflammation and Sensation (B.S.K.), the Marc and Jennifer Lipschultz Precision Immunology Institute (B.S.K.), and the Friedman Brain Institute (B.S.K.), Icahn School of Medicine at Mount Sinai, New York; Innovaderm Research, Montreal (R.B.); and Cara Therapeutics, Stamford, CT (K.N., C.M., N.S., A.J., J.C., J.G.).
N Engl J Med. 2023 Feb 9;388(6):511-517. doi: 10.1056/NEJMoa2210699.
Notalgia paresthetica is a neuropathic disorder characterized by pruritus in a circumscribed region of the upper back. Difelikefalin, a selective kappa opioid receptor agonist, has shown efficacy in other chronic pruritic conditions and is being investigated for the treatment of notalgia paresthetica.
In this phase 2, double-blind, placebo-controlled trial, we randomly assigned, in a 1:1 ratio, patients with moderate-to-severe pruritus caused by notalgia paresthetica to receive 2 mg of oral difelikefalin or placebo twice daily for 8 weeks. The primary outcome was the change from baseline at week 8 in the weekly mean score on the daily Worst Itch Numeric Rating Scale (WI-NRS; scores range from 0 [no itch] to 10 [worst itch imaginable]). The secondary clinical outcomes were itch-related quality-of-life and itch-related sleep measures.
A total of 126 patients were enrolled; 62 patients were assigned to receive difelikefalin, and 63 were assigned to receive placebo. One patient who had been assigned to receive difelikefalin withdrew consent before the first dose and is not included in the main analyses. The mean baseline WI-NRS score was 7.6 (indicating severe itch) in each group. The change from baseline in the weekly mean WI-NRS score at week 8 was -4.0 points in the difelikefalin group and -2.4 points in the placebo group (difference in change, -1.6 points; 95% confidence interval, -2.6 to -0.6; P = 0.001). The results for the secondary outcomes generally did not support those of the primary analysis. Headache, dizziness, constipation, and increased urine output occurred more frequently in the difelikefalin group than in the placebo group.
Among patients with notalgia paresthetica, oral treatment with difelikefalin resulted in modestly greater reductions in itch intensity scores than placebo over a period of 8 weeks but was associated with adverse events. Larger and longer trials are needed to assess the efficacy and safety of difelikefalin treatment in this disorder. (Funded by Cara Therapeutics; KOMFORT ClinicalTrials.gov number, NCT04706975.).
感觉异常性背疼是一种神经病理性疾病，其特征为上背部局限性区域的瘙痒。地洛啡肽，一种选择性 κ 阿片受体激动剂，已在其他慢性瘙痒疾病中显示出疗效，目前正在研究用于治疗感觉异常性背疼。
在这项 2 期、双盲、安慰剂对照试验中，我们按照 1:1 的比例将因感觉异常性背疼而导致中度至重度瘙痒的患者随机分为两组，分别接受每日两次口服 2 mg 地洛啡肽或安慰剂治疗，为期 8 周。主要结局是从基线到第 8 周每周平均每日最差瘙痒数字评定量表（WI-NRS；评分范围为 0 [无瘙痒]至 10 [可想象的最严重瘙痒]）的变化。次要临床结局为瘙痒相关的生活质量和瘙痒相关的睡眠指标。
共纳入 126 例患者；62 例患者被分配接受地洛啡肽治疗，63 例患者被分配接受安慰剂治疗。1 例已被分配接受地洛啡肽治疗的患者在首次给药前撤回了同意，并未纳入主要分析。两组患者的基线 WI-NRS 评分均为 7.6（表示严重瘙痒）。第 8 周时，地洛啡肽组每周平均 WI-NRS 评分的变化为-4.0 分，安慰剂组为-2.4 分（变化差值为-1.6 分；95%置信区间，-2.6 至-0.6；P=0.001）。次要结局的结果通常不支持主要分析的结果。与安慰剂组相比，地洛啡肽组头痛、头晕、便秘和尿失禁的发生率更高。
在感觉异常性背疼患者中，与安慰剂相比，口服地洛啡肽治疗在 8 周内可适度减轻瘙痒强度评分，但与不良反应相关。需要更大规模和更长时间的试验来评估地洛啡肽治疗这种疾病的疗效和安全性。（由 Cara Therapeutics 资助；KOMFORT ClinicalTrials.gov 编号，NCT04706975。）
