Division of Rheumatology, University of Alberta, Edmonton, Alberta, Canada.
Vasculitis Clinic, Division of Rheumatology, Department of Medicine, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
Expert Rev Clin Immunol. 2021 Jul;17(7):717-726. doi: 10.1080/1744666X.2021.1932466. Epub 2021 May 28.
: Anti-neutrophil cytoplasm autoantibodies (ANCA)-associated vasculitides (AAVs) are a group of rare heterogeneous diseases characterized by blood vessel inflammation resulting in organ destruction and death. Although various treatment strategies have resulted in marked improvement in vasculitis-specific outcomes, many patients with AAV continue to suffer from complications related to the prolonged use of glucocorticoids (GC) such as infections, metabolic abnormalities, and increased cardiovascular morbidity. Recently, activation of the alternative complement pathway has been implicated in the augmentation of the damage caused by AAV via the complement C5a receptor (C5aR1, CD88). Specifically targeting this pathway may lead to improved outcomes in patients with AAV.: In this article, we have summarized the rationale for targeting the complement pathway in AAV. The relevant pre-clinical, phase I, II and III findings with emphasis on the efficacy, and safety of avacopan, a new oral competitive inhibitor that interferes with the binding of C5a to C5aR1 (CD88), are reviewed.: These results are encouraging, may led to major changes in the treatment approach for AAV, and give rise to future studies utilizing complement inhibitors in AAV patients, and potentially in other immune mediated diseases.
抗中性粒细胞胞质抗体（ANCA）相关性血管炎（AAV）是一组罕见的异质性疾病，其特征为血管炎症导致器官损伤和死亡。尽管各种治疗策略已显著改善了血管炎的特定预后，但许多 AAV 患者仍因长期使用糖皮质激素（GC）而遭受相关并发症的困扰，如感染、代谢异常和心血管发病率增加。最近，补体替代途径的激活被认为通过补体 C5a 受体（C5aR1，CD88）加剧了 AAV 引起的损伤。特异性靶向该途径可能会改善 AAV 患者的预后。
在本文中，我们总结了在 AAV 中靶向补体途径的基本原理。重点介绍了 avacopan 的相关临床前、I 期、II 期和 III 期研究结果，这是一种新型口服竞争性抑制剂，可干扰 C5a 与 C5aR1（CD88）的结合。
这些结果令人鼓舞，可能会彻底改变 AAV 的治疗方法，并促使未来在 AAV 患者中以及可能在其他免疫介导性疾病中使用补体抑制剂的研究。
