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从传统到靶向:皮肌炎治疗的转变轨迹。

From traditional to targeted: the changing trajectory of therapies in dermatomyositis.

机构信息

Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, 221 Longwood Avenue, Boston, Massachusetts.

Section of Dermatology, The Children's Hospital of Philadelphia.

出版信息

Curr Opin Rheumatol. 2024 Nov 1;36(6):438-444. doi: 10.1097/BOR.0000000000001041. Epub 2024 Aug 13.

Abstract

PURPOSE OF REVIEW

New breakthroughs in our understanding of dermatomyositis (DM) have spawned the recent development of novel agents that specifically target key drivers in DM immunopathogenesis. This review aims to provide a comprehensive overview of new and forthcoming therapies for DM and to highlight their mechanisms of action, best evidence to date, and potential impact on disease management.

RECENT FINDINGS

Strategies that either counteract dysregulated interferon signaling [via the inhibition of interferon β, the type I interferon receptor subunit 1 (IFNAR1), or janus kinase (JAK)-signal transducer and activator of transcription (STAT) transduction] or induce durable autoreactive B cell depletion through chimeric antigen receptor (CAR) T-cell therapy appear to hold the most promise for sustained remission in DM.

SUMMARY

The trajectory of DM treatments is rapidly evolving, fueled by the unparalleled insights provided by multiomic studies and big data analysis pipelines. Targeted therapies that maximize both efficacy and safety have the potential to complement or replace traditional immunosuppressives and revolutionize the approach to the management of DM.

摘要

目的综述

对皮肌炎(DM)认识的新突破催生了针对 DM 免疫发病机制关键驱动因素的新型靶向药物的近期发展。本综述旨在全面概述 DM 的新型和即将出现的治疗方法,并强调其作用机制、迄今为止的最佳证据以及对疾病管理的潜在影响。

最近的发现

通过抑制干扰素β、I 型干扰素受体亚单位 1(IFNAR1)或 Janus 激酶(JAK)-信号转导和转录激活因子(STAT)转导来对抗失调的干扰素信号,或者通过嵌合抗原受体(CAR)T 细胞疗法诱导持久的自身反应性 B 细胞耗竭的策略,似乎最有希望在 DM 中实现持续缓解。

总结

DM 治疗的轨迹正在迅速发展,这得益于多组学研究和大数据分析管道提供的无与伦比的见解。靶向治疗在提高疗效和安全性的同时,有可能补充或替代传统免疫抑制剂,并彻底改变 DM 的治疗方法。

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