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巨细胞动脉炎(GCA)的治疗

Treatment of Giant Cell Arteritis (GCA).

作者信息

Régent Alexis, Mouthon Luc

机构信息

Service de Médecine Interne, Centre de Référence Maladies Auto-Immunes et Systémiques Rares d'Ile de France, APHP-CUP, Hôpital Cochin, F-75014 Paris, France.

Institut Cochin, Université de Paris Cité, F-75014 Paris, France.

出版信息

J Clin Med. 2022 Mar 24;11(7):1799. doi: 10.3390/jcm11071799.

Abstract

Giant cell arteritis (GCA) is the most frequent primary large-vessel vasculitis in individuals older than 50. Glucocorticoids (GCs) are considered the cornerstone of treatment. GC therapy is usually tapered over months according to clinical symptoms and inflammatory marker levels. Considering the high rate of GC-related adverse events in these older individuals, immunosuppressive treatments and biologic agents have been proposed as add-on therapies. Methotrexate was considered an alternative option, but its clinical impact was limited. Other immunosuppressants failed to demonstrate a significant favourable benefit/risk ratio. The approval of tocilizumab, an anti-interleukin 6 (IL-6) receptor inhibitor brought significant improvement. Indeed, tocilizumab had a noticeable effect on cumulative GCs' dose and relapse prevention. After the improvement in pathophysiological knowledge, other targeted therapies have been proposed, with anti-IL-12/23, anti-IL-17, anti-IL-1, anti-cytotoxic T-lymphocyte antigen 4, Janus kinase inhibitors or anti-granulocyte/macrophage colony stimulating factor therapies. These therapies are currently under evaluation. Interestingly, mavrilimumab, ustekinumab and, to a lesser extent, abatacept have shown promising results in phase 2 randomised controlled trials. Despite this recent progress, the value, specific condition and optimal application of each treatment remain undecided. In this review, we discuss the scientific rationale for each treatment and the therapeutic strategy.

摘要

巨细胞动脉炎(GCA)是50岁以上人群中最常见的原发性大血管血管炎。糖皮质激素(GCs)被认为是治疗的基石。GC治疗通常根据临床症状和炎症标志物水平在数月内逐渐减量。考虑到这些老年患者中与GC相关的不良事件发生率较高,免疫抑制治疗和生物制剂已被提议作为附加疗法。甲氨蝶呤曾被视为一种替代选择,但其临床效果有限。其他免疫抑制剂未能显示出显著的有利效益/风险比。抗白细胞介素6(IL-6)受体抑制剂托珠单抗的获批带来了显著改善。事实上,托珠单抗对累积GC剂量和预防复发有显著效果。在病理生理学知识取得进展后,人们提出了其他靶向治疗方法,包括抗IL-12/23、抗IL-17、抗IL-1、抗细胞毒性T淋巴细胞抗原4、Janus激酶抑制剂或抗粒细胞/巨噬细胞集落刺激因子疗法。这些疗法目前正在评估中。有趣的是,玛弗珠单抗、乌司奴单抗以及程度稍轻的阿巴西普在2期随机对照试验中已显示出有前景的结果。尽管有这些最新进展,但每种治疗的价值、具体情况和最佳应用仍未确定。在本综述中,我们讨论了每种治疗的科学依据和治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffe1/8999932/3d19b790810e/jcm-11-01799-g001.jpg

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