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比较现有用于治疗银屑病患者的JAK抑制剂。

Comparing available JAK inhibitors for treating patients with psoriasis.

作者信息

Funk Parker J, Perche Patrick O, Singh Rohan, Kelly Katherine A, Feldman Steven R

机构信息

Center for Dermatology Research, Department of Dermatology, Wake Forest School of Medicine, Winston-Salem.

Department of Pathology, Wake Forest School of Medicine, Winston-Salem.

出版信息

Expert Rev Clin Immunol. 2022 Mar;18(3):281-294. doi: 10.1080/1744666X.2022.2039121. Epub 2022 Feb 10.

Abstract

INTRODUCTION

Cytokine blockers have revolutionized the management of psoriasis. While efficacious, not all patients respond, and treatment may lose efficacy over time. Janus kinase (JAK) inhibitors target the Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) transduction cascade from transmitting cytokine signals in psoriasis.

AREAS COVERED

A PubMed search of phase I, II, and III clinical trials published between 2012 and 2021 utilizing the key terms: . Our search was expanded from clinical trials to further investigate the pathophysiology, standard of care, and safety and efficacy of JAK inhibitors in psoriasis.

EXPERT OPINION

Current treatments for psoriasis include topicals, phototherapy, and systemic therapy. The subcutaneous or intravenous route of biologic administration presents a challenge as patients often prefer oral medications over injections and because of anti-drug antibody development. Tofacitinib is effective and has an overall mild-to-moderate safety profile but includes an FDA black box warning for increased risk of cardiovascular events and malignancy. Other JAK inhibitors have an acceptable safety profile and are effective in early clinical trials. Poor topical medication adherence should be considered when evaluating JAK inhibitors. Oral JAK inhibitors may provide a preferable route of administration and improved clinical outcomes.

摘要

引言

细胞因子阻滞剂彻底改变了银屑病的治疗方式。虽然有效,但并非所有患者都有反应,而且治疗效果可能会随着时间推移而降低。Janus激酶(JAK)抑制剂通过阻断银屑病中细胞因子信号传导的Janus激酶/信号转导及转录激活因子(JAK/STAT)转导级联反应发挥作用。

涵盖领域

利用关键词对2012年至2021年间发表的I期、II期和III期临床试验进行PubMed检索。我们的检索范围从临床试验扩展到进一步研究JAK抑制剂在银屑病中的病理生理学、治疗标准以及安全性和有效性。

专家观点

目前银屑病的治疗方法包括局部用药、光疗和全身治疗。生物制剂的皮下或静脉给药途径存在挑战,因为患者通常更喜欢口服药物而非注射给药,且会产生抗药物抗体。托法替布有效且总体安全性为轻度至中度,但美国食品药品监督管理局(FDA)对其发出黑框警告,提示心血管事件和恶性肿瘤风险增加。其他JAK抑制剂具有可接受的安全性,且在早期临床试验中有效。在评估JAK抑制剂时应考虑局部用药依从性差的问题。口服JAK抑制剂可能提供更优的给药途径并改善临床结局。

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