Department of Dermatology, Centro Hospitalar Universitário do Porto, Edifício das Consultas Externas, Ex. CICAP, Rua D. Manuel II, s/n, 4100, Porto, Portugal.
Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, USA.
Am J Clin Dermatol. 2020 Dec;21(6):783-798. doi: 10.1007/s40257-020-00548-6.
Atopic dermatitis is a common, chronic, immune-mediated disease associated with several comorbidities. Elevated levels of T helper (Th)2, Th22, and also some Th1 and Th17 cytokines are found in atopic dermatitis skin lesions. Similar to psoriasis, there is a tendency towards increased use of more targeted therapies. However, there are still several unmet needs in the treatment of atopic dermatitis concerning long-term efficacy, tolerability, safety, route of administration, and cost. The increased knowledge of atopic dermatitis pathogenesis and the role of Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways has allowed the development of new compounds to inhibit this intracellular signaling pathway implicated in atopic dermatitis-related immune responses. Currently, JAK inhibitors are an important focus of therapeutic research for atopic dermatitis. Upadacitinib and abrocitinib are oral small molecules that inhibit the JAK/STAT pathway by selectively blocking JAK1. Data from phase II and III trials are encouraging, revealing that JAK1 inhibitors are effective and well-tolerated agents for moderate-to-severe atopic dermatitis. Selective JAK1 inhibitors may represent an important therapeutic option to be included in the treatment algorithm of atopic dermatitis, owing to oral administration and a favorable safety and tolerability profile. In this article, we review the current evidence on the efficacy and safety of oral selective JAK1 inhibitors for the treatment of atopic dermatitis.
特应性皮炎是一种常见的慢性免疫介导性疾病，与多种合并症相关。在特应性皮炎皮损中可发现辅助性 T 细胞（Th）2、Th22 以及一些 Th1 和 Th17 细胞因子水平升高。与银屑病类似，也倾向于更多地使用更具针对性的治疗方法。然而，在特应性皮炎的治疗中，仍存在一些尚未满足的需求，包括长期疗效、耐受性、安全性、给药途径和成本。特应性皮炎发病机制和 Janus 激酶/信号转导和转录激活因子（JAK/STAT）途径作用的知识增加，使得能够开发新的化合物来抑制特应性皮炎相关免疫反应中涉及的细胞内信号通路。目前，JAK 抑制剂是特应性皮炎治疗研究的重要焦点。Upadacitinib 和 abrocitinib 是口服小分子药物，通过选择性阻断 JAK1 来抑制 JAK/STAT 通路。来自 II 期和 III 期试验的数据令人鼓舞，表明 JAK1 抑制剂是治疗中重度特应性皮炎有效且耐受性良好的药物。选择性 JAK1 抑制剂可能是特应性皮炎治疗算法中纳入的一个重要治疗选择，因为其为口服给药，且具有良好的安全性和耐受性特征。本文综述了口服选择性 JAK1 抑制剂治疗特应性皮炎的疗效和安全性的现有证据。
