Stacey Hannah L, Francis Lucy, Smith Rona M, Jones Rachel B
Department of Nephrology, Addenbrooke's Hospital, Cambridge, UK.
Department of Medicine, University of Cambridge, Cambridge, UK.
Glomerular Dis. 2024 Dec 18;5(1):84-102. doi: 10.1159/000543159. eCollection 2025 Jan-Dec.
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis can be a life-threatening condition, characterized by necrotizing inflammation of small blood vessels. Major organ involvement, most commonly kidney and lung disease, is associated with significant morbidity and mortality. Intensive early immunosuppressive therapy is the cornerstone of management and has transformed ANCA-associated vasculitis (AAV) into a chronic relapsing condition. Remission induction with tapering glucocorticoids in combination with cyclophosphamide or rituximab is the standard of care for severe disease. Avacopan, an oral C5aR1 antagonist, has been approved for remission induction and helps minimize glucocorticoid exposure. Plasma exchange should be considered for severe kidney or life-threatening disease. Lower dose glucocorticoid induction regimens can be used without compromising remission rates. Remission maintenance therapy is recommended, and rituximab is usually first line over azathioprine. Mycophenolate mofetil (MMF) or methotrexate with low-dose glucocorticoids are third-line options. Immunosuppression-associated infection risk remains a concern, both during acute presentations and in the long term, highlighted by the impact of rituximab on humoral immunity and vaccine response during the COVID-19 pandemic. There remains an ongoing need for therapies that induce rapid remission and optimize kidney recovery while minimizing infection risk. Clinical trials are evaluating newer therapeutic options. Due to increasing treatment options, management should be individualized, balancing effective immunosuppression against comorbidities and frailty.
This review focuses on the treatment decision pathways for clinicians and patients in the management of severe AAV (granulomatosis with polyangiitis and microscopic polyangiitis). Key clinical trials, predictors of outcome, novel therapeutics, and practical steps to mitigate infection risk are discussed.
Immunosuppression regimens have been refined due to emerging evidence from clinical trials. Rituximab, avacopan, and reduced-dose glucocorticoid schedules have been the focus of recent studies. Infections and immunosuppression-induced immunodeficiency must be considered when determining individualized treatment.
抗中性粒细胞胞浆抗体（ANCA）相关血管炎可能是一种危及生命的疾病，其特征为小血管的坏死性炎症。主要器官受累，最常见的是肾脏和肺部疾病，与显著的发病率和死亡率相关。强化早期免疫抑制治疗是管理的基石，并已将ANCA相关血管炎（AAV）转变为一种慢性复发性疾病。使用逐渐减量的糖皮质激素联合环磷酰胺或利妥昔单抗进行诱导缓解是重症疾病的标准治疗方法。阿伐可泮，一种口服C5aR1拮抗剂，已被批准用于诱导缓解，并有助于尽量减少糖皮质激素暴露。对于重症肾脏疾病或危及生命的疾病，应考虑进行血浆置换。可以使用较低剂量的糖皮质激素诱导方案，而不影响缓解率。建议进行缓解维持治疗，利妥昔单抗通常是优于硫唑嘌呤的一线药物。霉酚酸酯（MMF）或甲氨蝶呤联合低剂量糖皮质激素是三线选择。免疫抑制相关的感染风险在急性发作期和长期都仍然是一个问题，利妥昔单抗在2019冠状病毒病大流行期间对体液免疫和疫苗反应的影响凸显了这一点。仍然持续需要能够诱导快速缓解并优化肾脏恢复同时将感染风险降至最低的治疗方法。临床试验正在评估更新的治疗选择。由于治疗选择的增加，管理应个体化，在有效的免疫抑制与合并症和虚弱之间取得平衡。
本综述重点关注临床医生和患者在重症AAV（肉芽肿性多血管炎和显微镜下多血管炎）管理中的治疗决策途径。讨论了关键临床试验、预后预测因素、新型治疗方法以及降低感染风险的实际步骤。
由于临床试验出现的新证据，免疫抑制方案已经得到完善。利妥昔单抗、阿伐可泮和减量糖皮质激素方案一直是近期研究的重点。在确定个体化治疗时，必须考虑感染和免疫抑制引起的免疫缺陷。
