Ständer Sonja, Yosipovitch Gil, Legat Franz J, Reich Adam, Paul Carle, Simon Dagmar, Naldi Luigi, Metz Martin, Tsianakas Athanasios, Pink Andrew, Fage Simon, Micali Giuseppe, Weisshaar Elke, Sundaram Hema, Metelitsa Andrei, Augustin Matthias, Wollenberg Andreas, Homey Bernhard, Fargnoli Maria Concetta, Sofen Howard, Korman Neil J, Skov Lone, Chen Xiaoxiao, Jabbar-Lopez Zarif K, Piketty Christophe, Kwatra Shawn G
Center for Chronic Pruritus and Department for Dermatology, University Hospital Münster, Münster, Germany.
Miami Itch Center, Miller School of Medicine at the University of Miami, Miami, Florida.
JAMA Dermatol. 2025 Feb 1;161(2):147-156. doi: 10.1001/jamadermatol.2024.4796.
Prurigo nodularis (PN) is a chronic and debilitating skin condition, characterized by intense itch with multiple nodular lesions. Nemolizumab demonstrated significant improvements in itch and skin nodules in adults with moderate to severe PN in a previous 16-week phase 3 study (OLYMPIA 2).
To assess the efficacy and occurrence of adverse events in adults with moderate to severe PN treated with nemolizumab vs those receiving placebo.
DESIGN, SETTING, AND PARTICIPANTS: OLYMPIA 1 was a multicenter, placebo-controlled, phase 3 randomized clinical trial, conducted from August 2020 to March 2023 at 77 centers across 10 countries in adults with moderate to severe PN (at least 20 nodules and an Investigator's Global Assessment [IGA] score ≥3) and Peak Pruritus Numerical Rating Scale (PP-NRS) score of at least 7.0; consisted of screening (up to 4 weeks), 24-week treatment, and 8-week follow-up periods.
Patients were randomized (2:1) to nemolizumab monotherapy, 30 mg or 60 mg (depending on baseline weight of less than 90 kg vs 90 kg or greater, respectively), or matching placebo administered every 4 weeks for 24 weeks.
The primary end points were the proportion of patients with itch response (≥4-point improvement from baseline in weekly average PP-NRS) and IGA success (score of 0/1 [clear/almost clear] and 2-grade or more improvement from baseline) at week 16.
Of 286 patients (mean [SD] age, 57.5 [13.0] years; mean [SD] body weight, 85.0 [20.7] kg; 166 [58.0%] female), 190 were randomized to receive nemolizumab, and 96 were randomized to placebo. A significantly greater proportion of patients assigned to nemolizumab vs placebo achieved itch response (111/190 [58.4%] vs 16/96 [16.7%]; Δ, 40.1% [95% CI, 29.4%-50.8%]; P < .001) and IGA success (50/190 [26.3%] vs 7/96 [7.3%]; Δ, 14.6% [95% CI, 6.7%-22.6%]; P = .003) at week 16. At week 24, the proportion of patients with itch response was 58.3% vs 20.4% (Δ, 38.7% [95% CI, 27.5%-49.9%]) in the ad hoc analysis, and IGA success was 58/190 (30.5%) vs 9/96 (9.4%) (Δ, 19.2% [95% CI, 10.3%-28.1%]) in the nemolizumab-treated vs placebo group. During the treatment period, 134 patients (71.7%) receiving nemolizumab vs 62 patients (65.3%) receiving placebo had at least 1 adverse event; most events were of mild to moderate severity.
In this randomized clinical trial, nemolizumab monotherapy led to clinically meaningful and statistically significant improvements in core signs and symptoms of PN.
ClinicalTrials.gov Identifier: NCT04501666.
结节性痒疹（PN）是一种慢性且使人衰弱的皮肤疾病，其特征为剧烈瘙痒并伴有多个结节性病变。在先前一项为期16周的3期研究（OLYMPIA 2）中，奈莫利珠单抗在中度至重度PN的成人患者中显示出瘙痒和皮肤结节方面的显著改善。
评估接受奈莫利珠单抗治疗的中度至重度PN成人患者与接受安慰剂治疗的患者相比的疗效及不良事件的发生情况。
设计、设置和参与者：OLYMPIA 1是一项多中心、安慰剂对照的3期随机临床试验，于2020年8月至2023年3月在10个国家的77个中心进行，纳入中度至重度PN（至少20个结节且研究者整体评估[IGA]评分≥3）且瘙痒峰值数字评定量表（PP-NRS）评分至少为7.0的成人患者；包括筛查（最长4周）、24周治疗期和8周随访期。
患者按2:1随机分组，接受奈莫利珠单抗单药治疗，30 mg或60 mg（分别取决于基线体重小于90 kg还是90 kg及以上），或匹配的安慰剂，每4周给药一次，共24周。
主要终点为第16周时出现瘙痒缓解（每周平均PP-NRS较基线改善≥4分）和IGA成功（评分为0/1[清除/几乎清除]且较基线改善2级或更多）的患者比例。
在286例患者中（平均[标准差]年龄，57.5[13.0]岁；平均[标准差]体重，85.0[20.7]kg；166例[58.0%]为女性），190例被随机分配接受奈莫利珠单抗治疗，96例被随机分配接受安慰剂治疗。与安慰剂组相比，接受奈莫利珠单抗治疗的患者在第16周时出现瘙痒缓解的比例显著更高（111/190[58.4%] vs 16/96[16.7%]；差值，40.1%[95%CI，29.4%-50.8%]；P < .001），IGA成功的比例也更高（50/190[26.3%] vs 7/96[7.3%]；差值，14.6%[95%CI，6.7%-22.6%]；P = .003）。在第24周的临时分析中，接受奈莫利珠单抗治疗的患者出现瘙痒缓解的比例为58.3%，而安慰剂组为20.4%（差值，38.7%[95%CI，27.5%-49.9%]），IGA成功的比例在奈莫利珠单抗治疗组为58/190（30.5%），安慰剂组为9/96（9.4%）（差值，19.2%[95%CI，10.3%-28.1%]）。在治疗期间，接受奈莫利珠单抗治疗的134例患者（71.7%）与接受安慰剂治疗的62例患者（65.3%）至少发生1次不良事件；大多数事件为轻度至中度严重程度。
在这项随机临床试验中，奈莫利珠单抗单药治疗使PN的核心体征和症状在临床意义和统计学上均有显著改善。
ClinicalTrials.gov标识符：NCT04501666。
