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阿泊替尼治疗 12 例日本特应性皮炎患者的真实世界疗效和安全性及外周血转录组分析

Real-world effectiveness and safety of abrocitinib in 12 Japanese patients with atopic dermatitis and transcriptome analysis with peripheral blood.

机构信息

Department of Dermatology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.

出版信息

J Dermatol. 2024 Jun;51(6):849-853. doi: 10.1111/1346-8138.17173. Epub 2024 Mar 3.

Abstract

Atopic dermatitis (AD) is a common chronic inflammatory skin disease characterized by recurrent, pruritic, and localized eczema. Various types of new drugs have been recently investigated for treating AD. The efficacy and safety of abrocitinib in treating AD has been reported in clinical trials, but the real-world data from Japan has not been reported. Herein, we analyzed 12 Japanese patients with AD treated with 100 mg of abrocitinib using our real-world data. We also performed transcriptome analysis with peripheral blood to investigate the effects of abrocitinib on cytokine expressions and inflammatory pathways in AD from three patients. This study included patients with moderate to severe AD treated with abrocitinib at Gunma University Hospital, Japan. All patients were systemic treatment-naïve. All patients received a 100-mg dose of abrocitinib daily, and used strong or very strong topical steroids and moisturizers. The Eczema Area and Severity Index (EASI) response analysis revealed that after 4 weeks, 25% (three of 12) of the cases reached a 75% reduction in the EASI score (EASI-75) and a 90% reduction in the EASI score (EASI-90). After 12 weeks, 83.3.% (10 of 12), 41.6% (five of 12), and 16.7% (two of 12) of the patients reached EASI-50, a 75% reduction in the EASI score (EASI-75), and EASI-90. Peak Pruritus Numerical Rating Scale was achieved in nine patients (75%) at week 12. The most frequent adverse reaction was acne (six cases [50%]). Gene Ontology pathway analysis using Differentially expressed genes from RNA sequencing analysis revealed attenuation of defense responses to biotic stimulus, virus, and cytokines. Th2 cytokine expression was not suppressed, but several chemokines, especially CXCL1, were suppressed by abrocitinib treatment. Our results indicate abrocitinib as a fast-acting and highly antipruritic agent that is effective for moderate skin eruptions.

摘要

特应性皮炎(AD)是一种常见的慢性炎症性皮肤病,其特征为反复发作、瘙痒和局部湿疹。最近已经研究了各种新型药物来治疗 AD。临床试验已经报道了阿布昔替尼治疗 AD 的疗效和安全性,但来自日本的真实世界数据尚未报道。在此,我们使用真实世界的数据分析了 12 例接受 100mg 阿布昔替尼治疗的 AD 日本患者。我们还对 3 例患者的外周血进行了转录组分析,以研究阿布昔替尼对 AD 中细胞因子表达和炎症途径的影响。本研究纳入了在日本群马大学医院接受阿布昔替尼治疗的中重度 AD 患者。所有患者均未接受过系统性治疗。所有患者均每日接受 100mg 阿布昔替尼治疗,并使用强效或极强效外用皮质类固醇和保湿剂。Eczema Area and Severity Index(EASI)应答分析显示,治疗 4 周后,25%(12 例中的 3 例)的病例达到 EASI 评分降低 75%(EASI-75),EASI 评分降低 90%(EASI-90)。治疗 12 周后,83.3%(12 例中的 10 例)、41.6%(12 例中的 5 例)和 16.7%(12 例中的 2 例)的患者达到 EASI-50、EASI 评分降低 75%(EASI-75)和 EASI-90。12 周时,9 例(75%)患者达到 Peak Pruritus Numerical Rating Scale。最常见的不良反应是痤疮(6 例[50%])。使用 RNA 测序分析差异表达基因的基因本体通路分析显示,对生物刺激、病毒和细胞因子的防御反应减弱。Th2 细胞因子表达未被抑制,但几种趋化因子,特别是 CXCL1,被阿布昔替尼治疗抑制。我们的结果表明,阿布昔替尼是一种快速起效和高度止痒的药物,对中度皮肤发作有效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6d8/11483892/8482b29f777e/JDE-51--g001.jpg

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