From Johns Hopkins Itch Center, Johns Hopkins University School of Medicine, Baltimore (S.G.K.); the Miami Itch Center, Miller School of Medicine at the University of Miami, Miami (G.Y.); the Department of Dermatology and Venereology, Medical University of Graz, Graz, Austria (F.J.L.); the Department of Dermatology, University of Rzeszow, Rzeszow (A.R.), and the Department of Dermatology, Venereology and Allergology, Wroclaw Medical University, Wroclaw (J.C.S.) - both in Poland; the Department of Dermatology, Medical University of Toulouse, Toulouse (C.P.), the Department of Dermatology, University Hospital, Nantes (S.B.), and the Department of Dermatology, University Hospital of Brest, Brest (L.M.) - all in France; the Department of Dermatology, Bern University Hospital, Bern (D.S.), the Department of Dermatology, Lausanne University Hospital CHUV and University of Lausanne, Lausanne, (C.C.), and Galderma, Zug (Z.K.J.L., C.P.) - all in Switzerland; the Academic Research Center, Centro Studi GISED, Bergamo, Italy (L.N.); the Lynde Institute for Dermatology & Lynderm Research and the Division of Dermatology, Department of Medicine (C.L.), University of Toronto, Toronto (C.L., M.S.); the Department of Dermatology and Allergology, Utrecht University-UMC, Utrecht, the Netherlands (M.S.D.B.-W.); the University Dermatology Group, University of California, San Diego, San Diego (W.K.N.), and First OC Dermatology Research, Fountain Valley (V.T.L.) - both in California; West Virginia Research Institute, Morgantown (R.G.); the Department of Dermatology, University of Cincinnati College of Medicine, Cincinnati (A.F.); Hospital de la Santa Creu i Sant Pau, Barcelona (E.S-B.); the Department of Dermatology, Ghent University Hospital, Ghent, Belgium (H.L.); Galderma R&D, Dallas (F.A.); and the Center for Chronic Pruritus, University Hospital, Munster, Germany (S.S.).
N Engl J Med. 2023 Oct 26;389(17):1579-1589. doi: 10.1056/NEJMoa2301333.
Prurigo nodularis is a chronic, debilitating, and severely pruritic neuroimmunologic skin disease. Nemolizumab, an interleukin-31 receptor alpha antagonist, down-regulates key pathways in the pathogenesis of prurigo nodularis.
In this phase 3, double-blind, multicenter, randomized trial, we assigned adults with moderate-to-severe prurigo nodularis to receive an initial 60-mg dose of nemolizumab followed by subcutaneous injections of 30 mg or 60 mg (depending on baseline weight) every 4 weeks for 16 weeks or matching placebo. The primary end points were an itch response (a reduction of ≥4 points on the Peak Pruritus Numerical Rating Scale [PP-NRS; scores range from 0 to 10, with higher scores indicating more severe itch]) and an Investigator's Global Assessment (IGA) response (a score of 0 [clear] or 1 [almost clear] on the IGA [scores range from 0 to 4] and a reduction from baseline to week 16 of ≥2 points). There were five key secondary end points.
A total of 274 patients underwent randomization; 183 were assigned to the nemolizumab group, and 91 to the placebo group. Treatment efficacy was shown with respect to both primary end points at week 16; a greater percentage of patients in the nemolizumab group than in the placebo group had an itch response (56.3% vs. 20.9%; strata-adjusted difference, 37.4 percentage points; 95% confidence interval [CI], 26.3 to 48.5), and a greater percentage in the nemolizumab group had an IGA response (37.7% vs. 11.0%; strata-adjusted difference, 28.5 percentage points; 95% CI, 18.8 to 38.2) (P<0.001 for both comparisons). Benefits were observed for the five key secondary end points: itch response at week 4 (41.0% vs. 7.7%), PP-NRS score of less than 2 at week 4 (19.7% vs. 2.2%) and week 16 (35.0% vs. 7.7%), and an improvement of 4 or more points on the sleep disturbance numerical rating scale (range, 0 [no sleep loss] to 10 [unable to sleep at all]) at week 4 (37.2% vs. 9.9%) and week 16 (51.9% vs. 20.9%) (P<0.001 for all comparisons). The most common individual adverse events were headache (6.6% vs. 4.4%) and atopic dermatitis (5.5% vs. 0%).
Nemolizumab monotherapy significantly reduced the signs and symptoms of prurigo nodularis. (Funded by Galderma; ClinicalTrials.gov number, NCT04501679; EudraCT number, 2019-004789-17.).
结节性痒疹是一种慢性、使人虚弱和严重瘙痒的神经免疫性皮肤疾病。Nemolizumab 是一种白细胞介素-31 受体 α 拮抗剂，可下调结节性痒疹发病机制中的关键途径。
在这项 3 期、双盲、多中心、随机试验中，我们将患有中重度结节性痒疹的成年人随机分配，接受初始 60 毫克剂量的 nemolizumab 治疗，然后根据基线体重接受皮下注射 30 毫克或 60 毫克（取决于基线体重），每 4 周一次，持续 16 周，或匹配安慰剂。主要终点是瘙痒反应（Peak Pruritus Numerical Rating Scale [PP-NRS] 降低≥4 分[评分范围为 0 至 10，得分越高表示瘙痒越严重]）和研究者全球评估（IGA）反应（IGA 评分为 0 [清除]或 1 [几乎清除] [IGA 评分范围为 0 至 4]，并且从基线到第 16 周的降低≥2 分）。有五个关键次要终点。
共有 274 名患者接受了随机分组；183 名患者被分配到 nemolizumab 组，91 名患者被分配到安慰剂组。在第 16 周时，两个主要终点均显示出治疗效果；nemolizumab 组中比安慰剂组中具有瘙痒反应的患者比例更高（56.3% vs. 20.9%；分层调整差异，37.4 个百分点；95%置信区间[CI]，26.3 至 48.5），并且 nemolizumab 组中 IGA 反应的患者比例更高（37.7% vs. 11.0%；分层调整差异，28.5 个百分点；95%CI，18.8 至 38.2）（两者均<0.001）。五个关键次要终点也观察到了益处：第 4 周时的瘙痒反应（41.0% vs. 7.7%）、第 4 周和第 16 周时的 PP-NRS 评分<2（19.7% vs. 2.2%和 35.0% vs. 7.7%），以及睡眠障碍数字评分量表（0 分表示无睡眠损失，10 分表示无法入睡）提高 4 分或更多分（第 4 周和第 16 周时，37.2% vs. 9.9%和 51.9% vs. 20.9%）（所有比较均<0.001）。最常见的单个不良事件是头痛（6.6% vs. 4.4%）和特应性皮炎（5.5% vs. 0%）。
Nemolizumab 单药治疗可显著减轻结节性痒疹的体征和症状。（由 Galderma 资助；ClinicalTrials.gov 编号，NCT04501679；EudraCT 编号，2019-004789-17。）
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