Abstract：
OBJECTIVE: This prospective single-arm trial with historic controls evaluated the efficacy and safety of treatment based on a combination of rituximab, intravenous cyclophosphamide, and corticosteroids (RCP) administered at lower cumulative doses for the induction of early remission in primary membranous nephropathy (PMN).
METHODS: We prospectively enrolled 30 high-risk PMN patients with persistent nephrotic syndrome (NS) and elevated antibodies to the phospholipase A2 receptor who underwent RCP therapy. We compared the effectiveness of RCP with that of historic controls who received rituximab-based therapy (RTX, n = 15) or cyclosporine + corticosteroids (CSA, n = 42). The primary outcomes were complete remission (CR) and overall remission (OR) by month 12 and the time to remission.
RESULTS: In the RCP group, the OR and CR rates by 12 months (97% and 60%) were higher than those in the RTX group (60% and 7%, P ≤ 0.009) and the CSA group (50% and 24%, P ≤ 0.003). The median time to OR (2.8 (1.6-3.9) months) was shorter compared to RTX (7.1 (3.4-17.5) months, P = 0.008) and CSA (7.3 (6.0-13.6) months, P < 0.001). In adjusted Cox regression, hazard ratios for OR and CR attainment for RCP versus other treatments were 5.2 (95% CI: 2.8-9.6) and 4.8 (95% CI: 2.2-10.3), respectively. Propensity score-matched group analyses confirmed these results. One serious adverse event occurred in the RCP group in the follow-up of 56 patient-years.
CONCLUSIONS: RCP therapy is considered effective and safe for inducing early remission in high-risk PMN patients.
METHODS: We prospectively enrolled 30 high-risk PMN patients with persistent nephrotic syndrome (NS) and elevated antibodies to the phospholipase A2 receptor who underwent RCP therapy. We compared the effectiveness of RCP with that of historic controls who received rituximab-based therapy (RTX, n = 15) or cyclosporine + corticosteroids (CSA, n = 42). The primary outcomes were complete remission (CR) and overall remission (OR) by month 12 and the time to remission.
RESULTS: In the RCP group, the OR and CR rates by 12 months (97% and 60%) were higher than those in the RTX group (60% and 7%, P ≤ 0.009) and the CSA group (50% and 24%, P ≤ 0.003). The median time to OR (2.8 (1.6-3.9) months) was shorter compared to RTX (7.1 (3.4-17.5) months, P = 0.008) and CSA (7.3 (6.0-13.6) months, P < 0.001). In adjusted Cox regression, hazard ratios for OR and CR attainment for RCP versus other treatments were 5.2 (95% CI: 2.8-9.6) and 4.8 (95% CI: 2.2-10.3), respectively. Propensity score-matched group analyses confirmed these results. One serious adverse event occurred in the RCP group in the follow-up of 56 patient-years.
CONCLUSIONS: RCP therapy is considered effective and safe for inducing early remission in high-risk PMN patients.
摘要：
目的：这项具有历史对照的前瞻性单臂试验评估了基于利妥昔单抗联合治疗的有效性和安全性，静脉注射环磷酰胺,和较低累积剂量的皮质类固醇（RCP）用于诱导原发性膜性肾病（PMN）的早期缓解。
方法：我们前瞻性招募了30例接受RCP治疗的持续性肾病综合征（NS）和磷脂酶A2受体抗体升高的高危PMN患者。我们比较了RCP与接受基于利妥昔单抗治疗的历史对照的有效性（RTX，n=15）或环孢菌素+皮质类固醇（CSA，n=42)。主要结果是到12个月时完全缓解（CR）和总体缓解（OR）以及缓解时间。
结果：在RCP组中，12个月的OR和CR率（97％和60％）高于RTX组（60％和7％，P≤0.009)和CSA组(50%和24%，P≤0.003)。与RTX（7.1（3.4-17.5）个月相比，OR的中位时间（2.8（1.6-3.9）个月）较短，P=0.008)和CSA(7.3(6.0-13.6)个月，P<0.001)。在调整后的Cox回归中，与其他治疗相比，RCP达到OR和CR的风险比分别为5.2（95％CI：2.8-9.6）和4.8（95％CI：2.2-10.3），分别。倾向得分匹配的组分析证实了这些结果。在56例患者-年的随访中，RCP组发生了1例严重不良事件。
结论：RCP治疗对于高危PMN患者早期缓解被认为是有效和安全的。
方法：我们前瞻性招募了30例接受RCP治疗的持续性肾病综合征（NS）和磷脂酶A2受体抗体升高的高危PMN患者。我们比较了RCP与接受基于利妥昔单抗治疗的历史对照的有效性（RTX，n=15）或环孢菌素+皮质类固醇（CSA，n=42)。主要结果是到12个月时完全缓解（CR）和总体缓解（OR）以及缓解时间。
结果：在RCP组中，12个月的OR和CR率（97％和60％）高于RTX组（60％和7％，P≤0.009)和CSA组(50%和24%，P≤0.003)。与RTX（7.1（3.4-17.5）个月相比，OR的中位时间（2.8（1.6-3.9）个月）较短，P=0.008)和CSA(7.3(6.0-13.6)个月，P<0.001)。在调整后的Cox回归中，与其他治疗相比，RCP达到OR和CR的风险比分别为5.2（95％CI：2.8-9.6）和4.8（95％CI：2.2-10.3），分别。倾向得分匹配的组分析证实了这些结果。在56例患者-年的随访中，RCP组发生了1例严重不良事件。
结论：RCP治疗对于高危PMN患者早期缓解被认为是有效和安全的。
