尼莫利珠单抗治疗中重度结节性痒疹的试验。

Trial of Nemolizumab in Moderate-to-Severe Prurigo Nodularis.

机构信息

From the Department of Dermatology and Center for Chronic Pruritus, University Hospital Münster, Münster (S.S.), the Department of Dermatology and Allergy, Christine Kühne Center for Allergy Research and Education, University Hospital, Bonn (T.B.), and the Department of Dermatology and Allergy, Ludwig Maximilian University of Munich, Munich (A.W.) - all in Germany; the Itch Center, Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami Hospital, Miami (G.Y.); the Department of Dermatology and Venereology, Medical University of Graz, Graz, Austria (F.J.L.); the Department of Dermatology, University Hospital of Nice, Nice (J.-P.L.), the Department of Dermatology, University of Toulouse, Toulouse (C. Paul), and the Department of Dermatology, University Hospital of Brest, Brest (L.M.) - all in France; the Department of Dermatology, Medical University of Lodz, Lodz (J.N.), and the Department of Dermatology, University of Rzeszow, Rzeszow (A.R.) - both in Poland; Galderma, Fort Worth, TX (F.A.); and Galderma, Lausanne, Switzerland (C. Piketty).

出版信息

N Engl J Med. 2020 Feb 20;382(8):706-716. doi: 10.1056/NEJMoa1908316.

DOI:10.1056/NEJMoa1908316

PMID:32074418

Abstract

BACKGROUND

Prurigo nodularis is a chronic pruritic skin disease with multiple nodular skin lesions. Nemolizumab is a monoclonal antibody targeting the interleukin-31 receptor, which is involved in the pathogenesis of prurigo nodularis.

METHODS

We conducted a 12-week, randomized, double-blind, phase 2 trial of nemolizumab (at a dose of 0.5 mg per kilogram of body weight) administered subcutaneously at baseline, week 4, and week 8, as compared with placebo, in patients with moderate-to-severe prurigo nodularis and severe pruritus. Moderate-to-severe prurigo nodularis was defined as 20 or more nodules, and severe pruritus was defined as a mean score of at least 7 for the worst daily intensity of pruritus on the numerical rating scale (scores range from 0 [no itch] to 10 [worst itch imaginable]). The primary outcome was the percent change from baseline in the mean peak score for pruritus on the numerical rating scale at week 4. Secondary outcomes included additional measures of itching and disease severity. Safety assessments were performed through week 18.

RESULTS

A total of 70 patients were randomly assigned in a 1:1 ratio to receive nemolizumab (34 patients) or placebo (36). The initial pruritus score on the numerical rating scale was 8.4 in each group. At week 4, the peak pruritus score on the numerical rating scale was reduced from baseline by 4.5 points (change, -53.0%) in the nemolizumab group, as compared with a reduction of 1.7 points (change, -20.2%) in the placebo group (difference, -32.8 percentage points; 95% confidence interval, -46.8 to -18.8; P<0.001). Results for secondary outcomes were in the same direction as for the primary outcome. Nemolizumab was associated with gastrointestinal symptoms (abdominal pain and diarrhea) and musculoskeletal symptoms.

CONCLUSIONS

Nemolizumab resulted in a greater reduction in pruritus and severity of skin lesions than placebo in patients with prurigo nodularis but was associated with adverse events. Larger and longer trials are needed to determine the durability and safety of nemolizumab for the treatment of prurigo nodularis. (Funded by Galderma; ClinicalTrials.gov number, NCT03181503.).

摘要

背景

结节性痒疹是一种慢性瘙痒性皮肤病，伴有多个结节性皮肤损伤。Nemolizumab 是一种针对白细胞介素-31 受体的单克隆抗体，该受体参与结节性痒疹的发病机制。

方法

我们进行了一项为期 12 周、随机、双盲、2 期试验，将 nemolizumab（剂量为每公斤体重 0.5 毫克）皮下注射，在基线时、第 4 周和第 8 周给药，与安慰剂相比，用于中度至重度结节性痒疹和严重瘙痒的患者。中度至重度结节性痒疹定义为 20 个或更多结节，严重瘙痒定义为数字评分量表上每日最严重瘙痒强度的平均评分至少为 7 分（评分范围为 0 [无瘙痒]至 10 [可想象的最严重瘙痒]）。主要结局是第 4 周时数字评分量表上瘙痒的平均峰值评分与基线相比的变化百分比。次要结局包括瘙痒和疾病严重程度的其他测量指标。安全性评估持续到第 18 周。

结果

共有 70 名患者以 1:1 的比例随机分配接受 nemolizumab（34 名患者）或安慰剂（36 名患者）。两组初始数字评分量表上的瘙痒评分均为 8.4。第 4 周时，nemolizumab 组数字评分量表上的瘙痒峰值评分较基线下降 4.5 分（变化，-53.0%），安慰剂组下降 1.7 分（变化，-20.2%）（差异，-32.8 个百分点；95%置信区间，-46.8 至-18.8；P<0.001）。次要结局的结果与主要结局一致。Nemolizumab 与胃肠道症状（腹痛和腹泻）和肌肉骨骼症状相关。

结论

与安慰剂相比，Nemolizumab 可使结节性痒疹患者的瘙痒和皮肤损伤严重程度更大程度地减轻，但与不良反应相关。需要更大规模和更长时间的试验来确定 Nemolizumab 治疗结节性痒疹的持久性和安全性。（由 Galderma 资助；ClinicalTrials.gov 编号，NCT03181503）。