Department of Biomedicine, Aarhus University, Aarhus, Denmark.
Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Autoimmun Rev. 2021 Jun;20(6):102829. doi: 10.1016/j.autrev.2021.102829. Epub 2021 Apr 16.
The primary vasculitides constitute a heterogeneous group of immune mediated diseases of incompletely understood pathogenesis currently classified by the size of blood vessels affected (Chapel Hill classification). In recent years, several drugs with well-characterized immunological targets have been tested in clinical trials in large vessel vasculitis and small vessel vasculitis. Such trials provide "reverse translational" or bedside to bench information about underlying pathogenic mechanisms. Therefore, the aim of this systematic literature review was to examine the evidence base for a more refined mechanistic immunological classification of vasculitis. A total of 40 studies (20 randomized controlled trials (RCTs), 16 prospective studies, 1 retrospective cohort study and 3 case series) were included for full qualitative assessment. RCTs concerning biologic therapy for large vessel vasculitis mainly supports interleukin 6 receptor inhibition (tocilizumab). RCTs concerning biologic therapy for granulomatosis with polyangiitis and microscopic polyangiitis mainly support anti-CD20 treatment (rituximab) and complement inhibition with a small molecule C5a receptor antagonist (avacopan) is an emerging treatment option. The biologic treatment of eosinophilic granulomatosis with polyangiitis is centered around interleukin 5 inhibition (mepolizumab). Studies on tumor necrosis factor alpha inhibition (adalimumab, infliximab, and etanercept) showed negative results in giant cell arteritis but some effect in Takayasu arteritis. Taken together, clinical studies with cytokine and cell specific drugs are dissecting the heterogeneous immunopathogenic mechanisms of vasculitis and support a mechanistic immunological classification. Especially, cytokine antagonism is pointing towards immunological distinctions between eosinophilic granulomatosis with polyangiitis and granulomatosis with polyangiitis/microscopic polyangiitis and differences between giant cell arteritis and Takayasu arteritis.
原发性血管炎是一组病因不明的免疫介导性疾病，其分类依据是受累血管的大小（Chapel Hill 分类）。近年来，几种具有明确免疫靶点的药物已在大动脉炎和小血管炎的临床试验中进行了测试。这些试验为潜在发病机制提供了“反向转化”或床旁到实验室的信息。因此，本系统文献复习的目的是探讨更精细的血管炎机制免疫分类的证据基础。共有 40 项研究（20 项随机对照试验（RCT）、16 项前瞻性研究、1 项回顾性队列研究和 3 项病例系列研究）进行了全面的定性评估。关于生物治疗大动脉炎的 RCT 主要支持白细胞介素 6 受体抑制（托珠单抗）。关于生物治疗肉芽肿性多血管炎和显微镜下多血管炎的 RCT 主要支持抗 CD20 治疗（利妥昔单抗）和用小分子 C5a 受体拮抗剂抑制补体（阿伐考帕）是一种新兴的治疗选择。嗜酸性肉芽肿性多血管炎的生物治疗以白细胞介素 5 抑制（美泊利单抗）为中心。肿瘤坏死因子-α 抑制（阿达木单抗、英夫利昔单抗和依那西普）的研究在巨细胞性动脉炎中显示出阴性结果，但在 Takayasu 动脉炎中则有一定效果。总之，细胞因子和细胞特异性药物的临床研究正在剖析血管炎的异质性免疫发病机制，并支持一种机制免疫分类。特别是细胞因子拮抗作用指出了嗜酸性肉芽肿性多血管炎和肉芽肿性多血管炎/显微镜下多血管炎之间的免疫学区别，以及巨细胞性动脉炎和 Takayasu 动脉炎之间的区别。
