Geetha Duvuru, Cortazar Frank B, Bruchfeld Annette, Kronbichler Andreas, Karras Alexandre, Nakhoul Georges N, Merkel Peter A, Bray Sarah, Bozeman Alana M, Jayne David R W
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
New York Nephrology Vasculitis and Glomerular Center, Albany, New York, USA.
Kidney Int Rep. 2025 Jun 2;10(8):2751-2765. doi: 10.1016/j.ekir.2025.05.041. eCollection 2025 Aug.
Kidney disease impacts long-term outcomes of patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). This analysis evaluated the effect of avacopan in a subgroup of patients with GPA or MPA and kidney involvement at baseline from the ADVOCATE trial.
The analysis included a study population of 268 patients (of 330 patients, 81.2%). Key efficacy outcomes were remission at week 26, sustained remission at week 52, and relapse after remission through week 52. Changes in estimated glomerular filtration rate (eGFR) were analyzed overall and stratified by baseline eGFR categories (≥ 90, 60-89, 45-59, 30-44, and 15-29 ml/min per 1.73 m). Additional outcomes were changes in albuminuria and hematuria, glucocorticoid (GC) use, glucocorticoid toxicity index (GTI), and safety.
Remission at week 26 and sustained remission at week 52, respectively, were respectively achieved by 99 of 134 (73.9%) and 91 of 134 (67.9%) patients in the avacopan group and 95 of 134 (70.9%) and 76 of 134 (56.7%) in the prednisone taper group. Relapse rate after remission was lower in the avacopan than in the prednisone taper group (9.4% vs. 20.9%; hazard ratio [95% confidence interval, CI]: 0.43 [0.22-0.85]). Recovery of kidney function, speed of reduction in albuminuria and hematuria, and changes in GTI favored the avacopan group. No new safety issues were reported for this subset of patients.
In patients with GPA or MPA with kidney involvement, treatment with an avacopan regimen compared with a prednisone taper regimen achieved similar rates of remission, improved recovery of kidney function, led to faster reduction in albuminuria and hematuria, and lowered GC-related toxicity, with an acceptable safety profile.
肾脏疾病会影响肉芽肿性多血管炎（GPA）和显微镜下多血管炎（MPA）患者的长期预后。本分析评估了在ADVOCATE试验中，阿伐可泮对基线时患有GPA或MPA且有肾脏受累的亚组患者的疗效。
该分析纳入了268例患者的研究人群（占330例患者的81.2%）。主要疗效指标为第26周时的缓解、第52周时的持续缓解以及至第52周缓解后的复发情况。对估计肾小球滤过率（eGFR）的变化进行总体分析，并按基线eGFR类别（≥90、60 - 89、45 - 59、30 - 44和15 - 29 ml/min per 1.73 m²）进行分层分析。其他指标包括蛋白尿和血尿的变化、糖皮质激素（GC）的使用、糖皮质激素毒性指数（GTI）以及安全性。
阿伐可泮组134例患者中分别有99例（73.9%）和91例（67.9%）在第26周时达到缓解和在第52周时达到持续缓解，泼尼松递减组134例患者中分别有95例（70.9%）和76例（56.7%）达到上述情况。缓解后的复发率在阿伐可泮组低于泼尼松递减组（9.4%对20.9%；风险比[95%置信区间，CI]：0.43[0.22 - 0.85]）。肾功能的恢复、蛋白尿和血尿减少的速度以及GTI的变化均有利于阿伐可泮组。该亚组患者未报告新的安全问题。
在患有GPA或MPA且有肾脏受累的患者中，与泼尼松递减方案相比，阿伐可泮方案治疗达到了相似的缓解率，改善了肾功能恢复，使蛋白尿和血尿更快减少，并降低了与GC相关的毒性，且安全性可接受。
