Assmann Gunter, Adjailia El-Baraa, Klapa Sebastian, von Allwoerden Katja, Amann Kerstin, Turkiewicz Ryszard, Radermacher Joerg, Lamprecht Peter
Department of Rheumatology, RUB University Hospital Minden JWK, Minden; and Jose-Carreras Centre for Immunogenetics and Gene Therapy, University Medical School of Saarland, Germany.
Department of Rheumatology and Clinical Immunology, University of Luebeck, Germany.
Clin Exp Rheumatol. 2025 Sep 9. doi: 10.55563/clinexprheumatol/7sz0zp.
Combination therapy of rituximab (RTX) and cyclophosphamide (CYC) can be considered for the induction of remission in severe anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). The presented study reports on the safety and efficacy of the complement C5a receptor inhibition with avacopan in the patients with severe ANCA-associated vasculitis treated with RTX and CYC in combination.
Retrospective analysis of the clinical course, response to and safety of avacopan in combination with RTX and CYC in 30 patients with severe ANCA-associated vasculitis with renal and at least two further organ-threatening involvement treated in two German referral centres.
The median observation time was 49 weeks (range 26-52). All patients achieved remission by week 24. Mean BVAS score was 22.8 (range 12-53) at baseline; mean eGFR increased from 44.0 ml/min per 1.73m2 at baseline to 57.6 ml/min per 1.73m2 by week 52. GC comedication was discontinued in 17 of 29 (58.6%) patients by week 24, and in 23 of 28 (82.1%) by week 52. One patient discontinued avacopan treatment due to urosepsis, another due to refractory disease. There was a significant difference in dialysis dependency of GC-free patients versus GC-treated patients at week 24 (n=1 vs. 4, p=0.048, OR 0.12, CI:0.01-1.25).
In this observational study, avacopan as GC-sparing agent appeared safe and efficacious in combination with RTX and CYC for remission induction in severe ANCA-associated vasculitis. In this subgroup, prospective studies are needed to determine the efficacy and safety of avacopan in combination with RTX and CYC for guidance of a GC-sparing strategy.
利妥昔单抗（RTX）与环磷酰胺（CYC）联合治疗可用于诱导重症抗中性粒细胞胞浆抗体（ANCA）相关性血管炎（AAV）缓解。本研究报告了在接受RTX与CYC联合治疗的重症ANCA相关性血管炎患者中，阿伐可泮抑制补体C5a受体的安全性和有效性。
对德国两家转诊中心收治的30例伴有肾脏受累且至少有另外两个器官受威胁的重症ANCA相关性血管炎患者，回顾性分析阿伐可泮联合RTX与CYC的临床病程、疗效及安全性。
中位观察时间为49周（范围26 - 52周）。所有患者在第24周时均实现缓解。基线时平均BVAS评分为22.8（范围12 - 53）；平均估算肾小球滤过率（eGFR）从基线时的每1.73m² 44.0 ml/min升至第52周时的每1.73m² 57.6 ml/min。29例患者中有17例（58.6%）在第24周时停用糖皮质激素辅助治疗，28例患者中有23例（82.1%）在第52周时停用。1例患者因尿脓毒症停用阿伐可泮治疗，另1例因疾病难治性停药。在第24周时，未使用糖皮质激素患者与使用糖皮质激素患者的透析依赖情况存在显著差异（n = 1 vs. 4，p = 0.048，比值比0.12，可信区间：0.01 - 1.25）。
在本观察性研究中，阿伐可泮作为糖皮质激素节约剂，与RTX和CYC联合用于诱导重症ANCA相关性血管炎缓解时似乎安全有效。在该亚组中，需要进行前瞻性研究以确定阿伐可泮与RTX和CYC联合应用的疗效和安全性，为糖皮质激素节约策略提供指导。
