The pipeline of immunomodulatory therapies in polymyalgia rheumatica and giant cell arteritis: A systematic review of clinical trials

IF 9.2 1区 医学 Q1 IMMUNOLOGY Autoimmunity reviews Pub Date : 2024-07-01 DOI:10.1016/j.autrev.2024.103590
Lou Kawka , Baptiste Chevet , Laurent Arnaud , Guillaume Becker , Guillermo Carvajal Alegria , Renaud Felten
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Abstract

Introduction

The objective of this systematic review was to provide an overview of current developments and potentially available therapeutic options for polymyalgia rheumatic (PMR) and giant cell arteritis (GCA), in the coming years.

Methods

We conducted a systematic review of 17 national and international clinical trial databases for all disease-modifying anti-rheumatic drugs (DMARDs) for PMR and GCA that are already marketed, in clinical development or withdrawn. The search was performed on January 2024, with the keywords “polymyalgia rheumatica” and “giant cell arteritis”. For each molecule, we only considered the study at the most advanced stage of clinical development.

Results

For PMR, a total of 15 DMARDs were identified: 2 conventional synthetic DMARDs (csDMARDs), 11 biologic DMARDs (bDMARDs) and 2 targeted synthetic DMARDs (tsDMARDs). For GCA, 18 DMARDs were identified: 2 csDMARDs, 14 bDMARDs and 2 tsDMARDs. Currently, there are only 2 approved corticosteroid-sparing therapies in these diseases, which both target the IL-6 signaling pathway, namely tocilizumab in GCA and sarilumab in PMR. Most of the molecules in current development are repurposed from from other conditions and clinical research in PMR/GCA seems to be mostly driven by the potential to repurpose existing treatments rather than by translational research.

Conclusion

This systematic review identified 23 DMARDs evaluated for PMR and GCA: 3 csDMARDs, 17 bDMARDs and 3 tsDMARDs. Several promising treatments are likely to be marketed in the coming years.

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多发性风湿痛和巨细胞动脉炎的免疫调节疗法:临床试验系统回顾。
导言:本系统综述旨在概述多发性风湿痛(PMR)和巨细胞动脉炎(GCA)目前的发展情况以及未来几年可能的治疗方案:我们对17个国家和国际临床试验数据库中所有已上市、处于临床开发阶段或已撤出的治疗多发性风湿痛和巨细胞性动脉炎的疾病修饰抗风湿药(DMARDs)进行了系统性检索。搜索时间为 2024 年 1 月,关键词为 "多发性风湿痛 "和 "巨细胞动脉炎"。对于每种分子,我们只考虑处于临床开发最后期阶段的研究:结果:针对多发性风湿性关节炎,共发现了 15 种 DMARDs:结果:对于 PMR,共发现了 15 种 DMARDs:2 种传统合成 DMARDs(csDMARDs)、11 种生物 DMARDs(bDMARDs)和 2 种靶向合成 DMARDs(tsDMARDs)。对于 GCA,确定了 18 种 DMARDs:2种csDMARDs、14种bDMARDs和2种tsDMARDs。目前,在这些疾病中仅有两种获批的皮质类固醇保留疗法,这两种疗法都以 IL-6 信号通路为靶点,即治疗 GCA 的托西珠单抗和治疗 PMR 的沙利单抗。目前正在开发的大多数分子都是从其他疾病中转用而来,而PMR/GCA的临床研究似乎主要是由转用现有疗法的潜力而非转化研究驱动的:本系统综述确定了23种针对PMR和GCA的DMARDs:3种csDMARDs、17种bDMARDs和3种tsDMARDs。未来几年,一些有前景的治疗方法可能会上市。
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来源期刊
Autoimmunity reviews
Autoimmunity reviews 医学-免疫学
CiteScore
24.70
自引率
4.40%
发文量
164
审稿时长
21 days
期刊介绍: Autoimmunity Reviews is a publication that features up-to-date, structured reviews on various topics in the field of autoimmunity. These reviews are written by renowned experts and include demonstrative illustrations and tables. Each article will have a clear "take-home" message for readers. The selection of articles is primarily done by the Editors-in-Chief, based on recommendations from the international Editorial Board. The topics covered in the articles span all areas of autoimmunology, aiming to bridge the gap between basic and clinical sciences. In terms of content, the contributions in basic sciences delve into the pathophysiology and mechanisms of autoimmune disorders, as well as genomics and proteomics. On the other hand, clinical contributions focus on diseases related to autoimmunity, novel therapies, and clinical associations. Autoimmunity Reviews is internationally recognized, and its articles are indexed and abstracted in prestigious databases such as PubMed/Medline, Science Citation Index Expanded, Biosciences Information Services, and Chemical Abstracts.
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