Department of Dermatology, Centro Hospitalar e Universitário do Porto, Porto, Portugal.
Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Porto, Portugal.
J Dermatolog Treat. 2020 Feb;31(1):33-40. doi: 10.1080/09546634.2019.1577549. Epub 2019 Feb 18.
Atopic dermatitis (AD) is the most common chronic inflammatory skin disease. Lesional skin of AD contains elevated levels of Th2, Th17, Th22 and Th1-citokines. With a growing movement toward use of targeted therapies, parallel to psoriasis, JAK inhibitors are an important focus of therapeutic research for AD. We review current evidence on the efficacy and safety of oral and topical JAK inhibitors for the treatment of AD. Several JAK inhibitors are in phase II and III clinical trials as oral therapies for moderate-to-severe AD or as topical treatments for mild-to-moderate AD. Results thus far are encouraging, with the majority of the patients achieving the primary outcome of their trial as well as a favorable safety profile. JAK inhibitors will most certainly be the first oral targeted option when topical therapy fails. With good oral bioavailability and lack of immunogenicity, they address some of the limitations of biologics. Yet to be defined is whether selective JAK 1 inhibitors or nonselective JAK inhibitors will provide the best equilibrium of efficacy versus side effects. Less clear is the position in the therapeutic ladder for topical JAK inhibitors; although, an unmeet need exists in the topical treatment of AD.
特应性皮炎(AD)是最常见的慢性炎症性皮肤病。AD 的皮损处含有高水平的 Th2、Th17、Th22 和 Th1-细胞因子。随着针对特定疗法的应用越来越多,与银屑病平行,JAK 抑制剂是 AD 治疗研究的一个重要焦点。我们回顾了口服和局部 JAK 抑制剂治疗 AD 的疗效和安全性的现有证据。几种 JAK 抑制剂正在进行 II 期和 III 期临床试验,作为中重度 AD 的口服治疗或轻中度 AD 的局部治疗。迄今为止的结果令人鼓舞,大多数患者达到了试验的主要终点,且具有良好的安全性特征。当局部治疗失败时,JAK 抑制剂肯定将成为第一个口服靶向选择。具有良好的口服生物利用度和缺乏免疫原性,它们解决了一些生物制剂的局限性。然而,尚待确定的是,选择性 JAK1 抑制剂还是非选择性 JAK 抑制剂将在疗效与副作用之间提供最佳平衡。局部 JAK 抑制剂在治疗阶梯中的地位尚不清楚;然而,AD 的局部治疗存在未满足的需求。