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评估外用JAK抑制剂作为特应性皮炎的一种治疗选择。

Evaluating topical JAK inhibitors as a treatment option for atopic dermatitis.

作者信息

Fardos Mohammad I, Singh Rohan, Perche Patrick O, Kelly Katherine A, Feldman Steven R

机构信息

Center for Dermatology Research, Department of Dermatology, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States.

Department of Pathology, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States.

出版信息

Expert Rev Clin Immunol. 2022 Mar;18(3):221-231. doi: 10.1080/1744666X.2022.1993061. Epub 2021 Oct 22.

Abstract

INTRODUCTION

Atopic dermatitis (AD) is a chronic, inflammatory skin condition mediated by cytokines that utilize the Janus Kinase/Signal Transducer and Activator of Transcription (JAK-STAT) signaling cascade. Topical JAK inhibitors are an emerging alternative in the treatment of AD.

AREAS COVERED

This expert review presents an overview of the underlying molecular pathophysiology of AD, current standards of care, and evaluation of the efficacy and safety of topical JAK inhibitors. A PubMed database search was utilized with a focus on the evidence from double-blind, randomized Phase I, II, and III clinical trials published between January 2015 and July 2021.

EXPERT OPINION

Current topical therapies for AD are efficacious but limited by their adverse side effects. Long-term topical corticosteroid use leads to loss of pigmentation, striae, and skin atrophy. Patients may be concerned about topical calcineurin inhibitors' black box warning of increased risk of malignancy. Topical crisaborole, a phosphodiesterase four inhibitor, is limited by application site burning. Topical ruxolitinib is a JAK inhibitor comparable to triamcinolone in efficacy without the adverse effects seen with long-term topical corticosteroid use. Although topical JAK inhibitors have promising efficacy and safety profiles, poor medication adherence common to topical treatments may limit their utility in a clinical setting.

摘要

引言

特应性皮炎(AD)是一种慢性炎症性皮肤病,由利用 Janus 激酶/信号转导子和转录激活子(JAK-STAT)信号级联的细胞因子介导。局部 JAK 抑制剂是 AD 治疗中一种新兴的替代方法。

涵盖领域

本专家综述概述了 AD 的潜在分子病理生理学、当前的护理标准以及局部 JAK 抑制剂的疗效和安全性评估。利用 PubMed 数据库进行搜索,重点关注 2015 年 1 月至 2021 年 7 月期间发表的双盲、随机 I、II 和 III 期临床试验的证据。

专家意见

目前用于 AD 的局部治疗方法有效,但受到其不良副作用的限制。长期使用局部皮质类固醇会导致色素沉着丧失、条纹和皮肤萎缩。患者可能担心局部钙调神经磷酸酶抑制剂的黑框警告,即恶性肿瘤风险增加。局部使用克立硼罗,一种磷酸二酯酶 4 抑制剂,受到用药部位烧灼感的限制。局部使用芦可替尼是一种 JAK 抑制剂,其疗效与曲安奈德相当,且没有长期使用局部皮质类固醇所出现的不良反应。尽管局部 JAK 抑制剂具有良好的疗效和安全性,但局部治疗常见的药物依从性差可能会限制其在临床环境中的应用。

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