ABSTRACT

Introduction

Janus kinase (JAK) inhibitors are emerging treatments in dermatology. Also known as JAKinibs, these agents target JAK-signal transducers and activators of transcription (JAK-STAT) pathway for intracellular signaling. Among the various immune-mediated inflammatory skin diseases that the JAK-STAT pathway plays a role in, atopic dermatitis (AD) is an important one. AD has a complex and multifactorial pathophysiology that is not fully understood. Immune dysregulation can result in epidermal barrier disruption and intensify atopic dermatitis. The newly developed abrocitinib (PF-04965842) selectively inhibits the JAK1 protein, which is believed to modulate cytokines involved in AD pathophysiology.

Areas covered

This work is a review of the current literature related to abrocitinib, including the phase I, II, and III clinical trials, for the treatment of AD. Immunological considerations of abrocitinib and JAK inhibition are also explored.

Expert opinion

Abrocitinib is among the first JAK inhibitors evaluated for the treatment of AD. Similar to other JAKinhibs that mechanistically block the signaling of several cytokines, abrocitinib possesses both positive and negative clinical attributes. Nonetheless, the risk-benefit profile of abrocitinib remains favorable. Up to 61% of AD patients achieve an EASI 75 response while a minority of responding patients experience mild to moderate symptoms related to tolerability.

中文翻译：

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Abrocitinib 用于治疗特应性皮炎。

摘要

介绍

Janus 激酶 (JAK) 抑制剂是皮肤病学中的新兴治疗方法。这些药物也称为 JAKinib，靶向 JAK 信号转导和转录激活因子 (JAK-STAT) 通路以进行细胞内信号传导。在 JAK-STAT 通路发挥作用的各种免疫介导的炎症性皮肤病中，特应性皮炎 (AD) 是重要的一种。AD 具有尚未完全了解的复杂且多因素的病理生理学。免疫失调可导致表皮屏障破坏并加剧特应性皮炎。新开发的 abrocitinib (PF-04965842) 选择性抑制 JAK1 蛋白，据信该蛋白可调节参与 AD 病理生理学的细胞因子。

覆盖区域

这项工作是对当前与 abrocitinib 相关的文献的综述，包括 I、II 和 III 期临床试验，用于治疗 AD。还探讨了 abrocitinib 和 JAK 抑制的免疫学考虑。

专家意见

Abrocitinib 是首批评估用于治疗 AD 的 JAK 抑制剂之一。与机械阻断几种细胞因子信号传导的其他 JAKinhib 类似，阿布替尼具有积极和消极的临床属性。尽管如此，阿布西替尼的风险收益状况仍然有利。高达 61% 的 AD 患者达到 EASI 75 反应，而少数有反应的患者出现与耐受性相关的轻度至中度症状。