Objectives Avacopan, a selective C5aR1 inhibitor, recently emerged as a glucocorticoid (GCs) sparing agent in ANCA-associated vasculitis (AAV). We aim to evaluate the tolerance and efficacy of avacopan given outside randomized clinical trials or with severe kidney involvement. Methods In this multicentre retrospective study, we reviewed the clinical charts of patients with AAV and contraindication to high dose of GCs who received avacopan 30 mg b.i.d plus standard-of-care regimen owing to the French early access program between 2020 and 2023. Efficacy and safety data were recorded using a standardized case report form. Results Among the 31 patients (median age 72 years), 10 had a relapsing AAV, twenty had anti-myeloperoxidase antibodies, and thirty had kidney vasculitis. Induction regimen included rituximab (n = 27), cyclophosphamide (n = 2), or both (n = 2). Five patients did not receive GCs. Despite rapid GCs tapering (which were withdrawn in 23 patients before month 3), 25 patients (81%) had a favorable outcome and no severe adverse event. The estimated glomerular filtration rate increased from 19 [15; 34] to 35 mL/min/1.73m2 [23; 45] at month 12 (p< 0.05), independently of kidney biopsies findings. One patient developed refractory AAV and two had a relapse while receiving avacopan. At month 12, ANCA remained positive in 10/18 patients (55.5%). Two patients developed severe adverse events leading to a withdrawal of avacopan (hepatitis and age-related macular degeneration). Conclusions The GCs’ sparing effect of avacopan was confirmed, even in patients with severe kidney vasculitis, but further studies are required to identify the optimal dosing of GCs when avacopan is used.

中文翻译：

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Avacopan 治疗抗中性粒细胞胞质抗体相关性血管炎：一项多中心真实世界研究


目标 Avacopan 是一种选择性 C5aR1 抑制剂，最近作为 ANCA 相关血管炎 (AAV) 的糖皮质激素 (GC) 节约剂出现。我们的目的是在随机临床试验之外或严重肾脏受累的情况下评估 avacopan 的耐受性和疗效。方法 在这项多中心回顾性研究中，我们回顾了 2020 年至 2023 年间因法国早期进入计划而接受 avacopan 30 mg bid 加标准护理方案的 AAV 患者和高剂量 GC 禁忌症患者的临床图表。使用标准化病例报告表记录安全数据。结果 31 名患者（中位年龄 72 岁）中，10 名患有复发性 AAV，20 名患有抗髓过氧化物酶抗体，30 名患有肾血管炎。诱导方案包括利妥昔单抗 (n = 27)、环磷酰胺 (n = 2) 或两者兼用 (n = 2)。 5 名患者未接受 GC。尽管 GC 逐渐减量（23 名患者在第 3 个月前停药），但 25 名患者 (81%) 取得了良好的结果，并且没有严重不良事件。估计的肾小球滤过率从 19 增加[15; 34] 至 35 毫升/分钟/1.73 平方米 [23； 45] 第 12 个月 (p< 0.05)，与肾活检结果无关。一名患者出现难治性 AAV，两名患者在接受阿瓦科潘治疗期间病情复发。第 12 个月时，10/18 名患者 (55.5%) 的 ANCA 仍呈阳性。两名患者出现严重不良事件，导致 avacopan 停药（肝炎和年龄相关性黄斑变性）。结论 avacopan 的 GC 保护作用得到证实，即使在患有严重肾血管炎的患者中也是如此，但需要进一步研究以确定使用 avacopan 时 GC 的最佳剂量。