Kwatra Shawn G, Bordeaux Zachary A, Parthasarathy Varsha, Kollhoff Alexander L, Alajmi Ali, Pritchard Thomas, Cornman Hannah L, Kambala Anusha, Lee Kevin K, Manjunath Jaya, Ma Emily Z, Dillen Carly, Kwatra Madan M
Department of Dermatology, University of Maryland School of Medicine, Baltimore.
Maryland Itch Center, University of Maryland School of Medicine, Baltimore.
JAMA Dermatol. 2024 Jul 1;160(7):717-724. doi: 10.1001/jamadermatol.2024.1464.
Prurigo nodularis (PN) and chronic pruritus of unknown origin (CPUO) are chronic pruritic diseases that dramatically impair quality of life, but therapeutic options are limited. Abrocitinib, a Janus kinase 1 inhibitor, represents a promising therapy for both conditions.
To assess the efficacy and safety of 200-mg oral abrocitinib administered once daily in adults with moderate to severe PN or CPUO.
DESIGN, SETTING, AND PARTICIPANTS: This phase 2, open-label, nonrandomized controlled trial conducted between September 2021 and July 2022 took place at a single center in the US. A total of 25 adult patients with moderate to severe PN or CPUO were screened. Ten patients with PN and 10 patients with CPUO were enrolled. All 20 patients completed the 12-week treatment period, 18 of whom completed the 4-week follow-up period.
Abrocitinib, 200 mg, by mouth once daily for 12 weeks.
The primary efficacy end point was the percent change in weekly Peak Pruritus Numerical Rating Scale (PP-NRS) scores from baseline to week 12. Key secondary end points included the percentage of patients achieving at least a 4-point reduction in weekly PP-NRS score from baseline to week 12 and the percent change in Dermatology Life Quality Index (DLQI) scores.
A total of 10 patients with PN (mean [SD] age, 58.6 [13.1] years; all were female) and 10 patients with CPUO (mean [SD] age, 70.7 [5.6] years; 2 were female) enrolled in the study. The mean (SD) baseline PP-NRS score was 9.2 (1.0) for PN and 8.2 (1.2) for CPUO. PP-NRS scores decreased by 78.3% in PN (95% CI, -118.5 to -38.1; P < .001) and 53.7% in CPUO (95% CI, -98.8 to -8.6; P = .01) by week 12. From baseline to week 12, 8 of 10 patients with PN and 6 of 10 patients with CPUO achieved at least a 4-point improvement on the PP-NRS. Both groups experienced significant improvement in quality of life as demonstrated by percent change in DLQI scores (PN: -53.2% [95% CI, -75.3% to -31.1%]; P = .002; CPUO: -49.0% [95% CI, -89.6% to -8.0%]; P = .02). The most common adverse event among patients was acneiform eruption in 2 of 20 patients (10%). No serious adverse events occurred.
The results of this nonrandomized controlled trial suggest that abrocitinib monotherapy may be effective and tolerated well in adults with PN or CPUO. Randomized, double-blind, placebo-controlled trials are warranted to validate these findings.
ClinicalTrials.gov Identifier: NCT05038982.
结节性痒疹（PN）和不明原因的慢性瘙痒（CPUO）是严重影响生活质量的慢性瘙痒性疾病，但治疗选择有限。阿布昔替尼是一种Janus激酶1抑制剂，有望用于治疗这两种疾病。
评估每日口服一次200mg阿布昔替尼治疗中度至重度PN或CPUO成人患者的疗效和安全性。
设计、地点和参与者：这项2期开放标签、非随机对照试验于2021年9月至2022年7月在美国的一个中心进行。共筛选了25例中度至重度PN或CPUO的成年患者。10例PN患者和10例CPUO患者入组。所有20例患者均完成了12周的治疗期，其中18例完成了4周的随访期。
口服200mg阿布昔替尼，每日一次，共12周。
主要疗效终点为从基线到第12周每周瘙痒峰值数字评定量表（PP-NRS）评分的变化百分比。关键次要终点包括从基线到第12周每周PP-NRS评分至少降低4分的患者百分比以及皮肤病生活质量指数（DLQI）评分的变化百分比。
共有10例PN患者（平均[标准差]年龄，58.6[13.1]岁；均为女性）和10例CPUO患者（平均[标准差]年龄，70.7[5.6]岁；2例为女性）入组本研究。PN患者的平均（标准差）基线PP-NRS评分为9.2（1.0），CPUO患者为8.2（1.2）。到第12周时，PN患者的PP-NRS评分下降了78.3%（95%置信区间，-118.5至-38.1；P＜0.001），CPUO患者下降了53.7%（95%置信区间，-98.8至-8.6；P = 0.01）。从基线到第12周，10例PN患者中有8例、10例CPUO患者中有6例的PP-NRS评分至少改善了4分。两组患者的生活质量均有显著改善，DLQI评分变化百分比表明了这一点（PN：-53.2%[95%置信区间，-75.3%至-31.1%]；P = 0.002；CPUO：-49.0%[95%置信区间，-89.6%至-8.0%]；P = 0.02）。患者中最常见的不良事件是20例中有2例（10%）出现痤疮样皮疹。未发生严重不良事件。
这项非随机对照试验的结果表明，阿布昔替尼单药治疗可能对PN或CPUO成人患者有效且耐受性良好。有必要进行随机、双盲、安慰剂对照试验来验证这些发现。
ClinicalTrials.gov标识符：NCT05038982。
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