Efficacy and Safety of Abrocitinib in Prurigo Nodularis and Chronic Pruritus of Unknown Origin: A Nonrandomized Controlled Trial.

IF 11.5 1区医学 Q1 DERMATOLOGY JAMA dermatology Pub Date : 2024-07-01 DOI:10.1001/jamadermatol.2024.1464

Shawn G Kwatra, Zachary A Bordeaux, Varsha Parthasarathy, Alexander L Kollhoff, Ali Alajmi, Thomas Pritchard, Hannah L Cornman, Anusha Kambala, Kevin K Lee, Jaya Manjunath, Emily Z Ma, Carly Dillen, Madan M Kwatra

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Abstract

Importance: 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.

Objective: 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.

Intervention: Abrocitinib, 200 mg, by mouth once daily for 12 weeks.

Main outcomes and measures: 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.

Results: 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.

Conclusions and relevance: 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.

Trial registration: ClinicalTrials.gov Identifier: NCT05038982.

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阿昔替尼治疗结节性瘙痒症和不明原因慢性瘙痒症的有效性和安全性：非随机对照试验。

重要性：结节性瘙痒症（PN）和原因不明的慢性瘙痒症（CPUO）是严重影响生活质量的慢性瘙痒症，但治疗方案却很有限。阿罗西替尼是一种Janus激酶1抑制剂，是治疗这两种疾病的一种很有前景的疗法：评估每日一次口服 200 毫克阿罗西替尼治疗中重度 PN 或 CPUO 成人患者的疗效和安全性：该 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 名中重度 PN 或 CPUO 成年患者。10 名 PN 患者和 10 名 CPUO 患者入选。所有20名患者均完成了为期12周的治疗，其中18名患者完成了为期4周的随访：阿罗西替尼，200 毫克，口服，每日一次，疗程 12 周：主要疗效终点是瘙痒峰值数字评分量表（PP-NRS）每周评分从基线到第12周的变化百分比。主要次要终点包括从基线到第12周每周PP-NRS评分至少降低4分的患者比例，以及皮肤科生活质量指数（DLQI）评分的变化百分比：共有 10 名 PN 患者（平均 [SD] 年龄为 58.6 [13.1] 岁，均为女性）和 10 名 CPUO 患者（平均 [SD] 年龄为 70.7 [5.6] 岁，其中 2 人为女性）参加了研究。PN和CPUO患者的PP-NRS基线得分分别为9.2（1.0）和8.2（1.2）。PN 的 PP-NRS 评分下降了 78.3%（95% CI，-118.5 至 -38.1；P 结论和相关性：这项非随机对照试验的结果表明，阿罗西替尼单药治疗对成人 PN 或 CPUO 患者可能有效且耐受性良好。需要进行随机、双盲、安慰剂对照试验来验证这些结果：试验注册：ClinicalTrials.gov Identifier：试验注册：ClinicalTrials.gov Identifier：NCT05038982。

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来源期刊

JAMA dermatology DERMATOLOGY-

CiteScore

14.10

自引率

5.50%

发文量

300

期刊介绍： JAMA Dermatology is an international peer-reviewed journal that has been in continuous publication since 1882. It began publication by the American Medical Association in 1920 as Archives of Dermatology and Syphilology. The journal publishes material that helps in the development and testing of the effectiveness of diagnosis and treatment in medical and surgical dermatology, pediatric and geriatric dermatology, and oncologic and aesthetic dermatologic surgery. JAMA Dermatology is a member of the JAMA Network, a consortium of peer-reviewed, general medical and specialty publications. It is published online weekly, every Wednesday, and in 12 print/online issues a year. The mission of the journal is to elevate the art and science of health and diseases of skin, hair, nails, and mucous membranes, and their treatment, with the aim of enabling dermatologists to deliver evidence-based, high-value medical and surgical dermatologic care. The journal publishes a broad range of innovative studies and trials that shift research and clinical practice paradigms, expand the understanding of the burden of dermatologic diseases and key outcomes, improve the practice of dermatology, and ensure equitable care to all patients. It also features research and opinion examining ethical, moral, socioeconomic, educational, and political issues relevant to dermatologists, aiming to enable ongoing improvement to the workforce, scope of practice, and the training of future dermatologists. JAMA Dermatology aims to be a leader in developing initiatives to improve diversity, equity, and inclusion within the specialty and within dermatology medical publishing.

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