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风湿性多肌痛和巨细胞动脉炎的免疫调节治疗流程:一项临床试验的系统评价

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

作者信息

Kawka Lou, Chevet Baptiste, Arnaud Laurent, Becker Guillaume, Carvajal Alegria Guillermo, Felten Renaud

机构信息

Service de Rhumatologie, Centre National de Référence des Maladies Auto-immunes et Systémiques Rares (RESO), Hôpitaux Universitaires de Strasbourg, F-67000 Strasbourg, France.

UMR 1227 Lymphocytes B et auto-immunité, université de Brest, Inserm, CHU de Brest, Brest, France; Service de Rhumatologie, Hôpital de la Cavale Blanche, CHU de Brest, Bd Tanguy-Prigent, 29200 Brest, France.

出版信息

Autoimmun Rev. 2024 Jul-Aug;23(7-8):103590. doi: 10.1016/j.autrev.2024.103590. Epub 2024 Aug 7.

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disease-modifying anti-rheumatic drugs (DMARDs) for PMR and GCA that are already marketed, in clinical development or withdrawn.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.

摘要

引言

本系统评价的目的是概述未来几年风湿性多肌痛(PMR)和巨细胞动脉炎(GCA)的当前进展及潜在的可用治疗选择。

方法

我们对17个国家和国际临床试验数据库进行了系统评价,以查找已上市、处于临床开发阶段或已撤市的用于PMR和GCA的所有改善病情抗风湿药物(DMARDs)。检索于2024年1月进行,关键词为“风湿性多肌痛”和“巨细胞动脉炎”。对于每个分子,我们仅考虑临床开发最先进阶段的研究。

结果

对于PMR,共鉴定出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,鉴定出18种DMARDs:2种csDMARDs、14种bDMARDs和2种tsDMARDs。目前,这些疾病中仅有2种获批的糖皮质激素节省疗法,均靶向IL-6信号通路,即GCA中的托珠单抗和PMR中的萨瑞鲁单抗。当前正在开发的大多数分子是从其他病症中重新利用的,PMR/GCA的临床研究似乎主要由重新利用现有治疗方法的潜力驱动,而非转化研究。

结论

本系统评价确定了23种针对PMR和GCA进行评估的DMARDs:3种csDMARDs、17种bDMARDs和3种tsDMARDs。未来几年可能会有几种有前景的治疗方法上市。

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