Hu Xiaofan, Ren Hong, Xu Jing, Gao Chenni, Wu Yifan, Ouyang Yan, Lin Li, Li Xiao, Liu Na, Wang Weiming, Xie Jingyuan, Chen Nan
Department of Nephrology, School of Medicine, Institute of Nephrology, Shanghai Ruijin Hospital, Shanghai Jiao Tong University, Shanghai, China.
Biomedical and health informatics, University of Washington, Seattle, WA, USA.
Kidney Dis (Basel). 2024 Jul 29;10(5):359-368. doi: 10.1159/000540548. eCollection 2024 Oct.
Previous studies have shown that rituximab (RTX) and cyclic oral corticosteroid-cyclophosphamide (CTX) regimens have similar effects on primary membranous nephropathy (PMN). However, no studies have compared RTX with an intravenous CTX regimen, which is more commonly used in China and requires fewer cumulative CTX doses.
We prospectively assigned 141 PMN patients with baseline proteinuria ≥4 g/24 h, serum albumin <30 g/L, and eGFR ≥30 mL/min × 1.73 m despite at least 3 months of treatment with ACEI and/or ARB to the RTX group (375 mg/m per injection per week × 4 injections) or to the CTX group (prednisone 0.8 mg/kg/day and intravenous CTX 500 mg/m per month until the total dose reached 6-8 g). The primary endpoint was defined as a combination of partial remission or complete remission at 12 months.
By the end of 12 months, 43 of 70 patients (61.43%) in the RTX group and 54 of 71 patients (76.06%) in the CTX group reached the primary endpoint ( = 0.06). Significantly fewer patients in the RTX group achieved complete remission than the CTX group (14.29% vs. 33.80%, = 0.01). The adverse events rate was similar between the RTX group and the CTX group (28.57% vs. 40.85%, = 0.13). In subgroup analysis, we found that fewer patients from the RTX group achieved the primary endpoint than the CTX group (48.65% vs. 74.29%, = 0.03) among patients with massive proteinuria (urine protein ≥8 g/24 h). During the observational phase, 61 patients in the RTX group and 58 in the CTX group completed 24 months of follow-up, exhibiting similar remission rates (RTX vs. CTX: 75.41% vs. 68.97%, = 0.54).
Our results show that the intravenous CTX regimen has similar safety and efficacy with higher rates of early complete remission than RTX in the treatment of PMN patients.
既往研究表明，利妥昔单抗（RTX）与口服糖皮质激素 - 环磷酰胺（CTX）方案对原发性膜性肾病（PMN）的疗效相似。然而，尚无研究将RTX与静脉注射CTX方案进行比较，后者在中国更常用且累积CTX剂量要求更少。
我们前瞻性地将141例尽管接受了至少3个月的ACEI和/或ARB治疗，但基线蛋白尿≥4 g/24 h、血清白蛋白<30 g/L且估算肾小球滤过率（eGFR）≥30 mL/min×1.73 m²的PMN患者分为RTX组（每周每平方米375 mg，共注射4次）或CTX组（泼尼松0.8 mg/kg/天，每月静脉注射CTX 500 mg/m²，直至总剂量达到6 - 8 g）。主要终点定义为12个月时部分缓解或完全缓解。
到12个月末，RTX组70例患者中有43例（61.43%），CTX组71例患者中有54例（76.06%）达到主要终点（P = 0.06）。RTX组达到完全缓解的患者明显少于CTX组（14.29%对33.80%，P = 0.01）。RTX组和CTX组的不良事件发生率相似（28.57%对40.85%，P = 0.13）。在亚组分析中，我们发现大量蛋白尿（尿蛋白≥8 g/24 h）患者中，RTX组达到主要终点的患者少于CTX组（48.65%对74.29%，P = 0.03）。在观察期内，RTX组61例患者和CTX组58例患者完成了24个月的随访，缓解率相似（RTX组对CTX组：75.41%对68.97%，P = 0.54）。
我们的结果表明，在治疗PMN患者时，静脉注射CTX方案具有相似的安全性和疗效，且早期完全缓解率高于RTX。
