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JAK抑制剂与黑框警告:JAK抑制剂的未来何去何从?

JAK inhibitors and black box warnings: what is the future for JAK inhibitors?

作者信息

Tokareva Kate, Reid Pankti, Yang Victor, Liew David, Peterson Alexander C, Baraff Aaron, Giles Jon, Singh Namrata

机构信息

Medical Student, University of Washington, Seattle, WA, USA.

Division of Rheumatology and Committee on Clinical Pharmacology and Pharmacogenomics, Department of Medicine, University of Chicago Biological Sciences Division, Chicago, IL, USA.

出版信息

Expert Rev Clin Immunol. 2023 Jul-Dec;19(11):1385-1397. doi: 10.1080/1744666X.2023.2249237. Epub 2023 Sep 4.

Abstract

INTRODUCTION

Janus kinase inhibitors (JAKi) have dramatically improved the treatment of various autoimmune and myeloproliferative disorders. Recently, concern has arisen regarding their safety in patients with rheumatoid arthritis.

AREAS COVERED

Here, we provide a comprehensive summary of the major current and emerging JAKi and their indications, address recent studies on comparative safety, and provide insight into their future and use. We emphasize that the application of the research findings on a case-by-case basis should consider a patient's age, comorbidities, disease for which JAKi is being considered, disease activity, the JAKi target(s), alternate treatment options available for the patient, and the planned duration of JAKi.

EXPERT OPINION

Rheumatologists are used to prescribing therapies in which a risk-to-benefit assessment is required as well as to screening and monitoring the safety of medications. Thus, rheumatologists are already practiced in applying specific criteria to effectively screen and monitor patients who are candidates for JAKi therapy. Ongoing research will help to clarify any mechanisms underlying differential safety signals between JAK and other therapies, what the balance between risk and efficacy is, who the susceptible subpopulations are, and whether safety signals are shared between different JAKis and across indications.

摘要

引言

Janus激酶抑制剂(JAKi)显著改善了多种自身免疫性疾病和骨髓增殖性疾病的治疗。最近,人们对其在类风湿关节炎患者中的安全性产生了担忧。

涵盖领域

在此,我们全面总结了当前主要和新兴的JAKi及其适应症,阐述了近期关于比较安全性的研究,并对其未来发展和应用提供见解。我们强调,根据具体情况应用研究结果时,应考虑患者的年龄、合并症、考虑使用JAKi治疗的疾病、疾病活动度、JAKi的靶点、患者可用的替代治疗方案以及JAKi的计划使用时长。

专家观点

风湿病学家习惯于开具需要进行风险效益评估以及筛查和监测药物安全性的疗法。因此,风湿病学家已经在应用特定标准来有效筛查和监测JAKi治疗候选患者方面积累了经验。正在进行的研究将有助于阐明JAK与其他疗法之间不同安全信号的潜在机制、风险与疗效的平衡、易感亚群是谁,以及不同JAKi之间和不同适应症之间是否存在共同的安全信号。

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