Nephrology Division, Hospital Universitario Fundación Alcorcón, Madrid, Spain.
Nephrology Division, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain.
Kidney Int. 2021 Apr;99(4):986-998. doi: 10.1016/j.kint.2020.10.014. Epub 2020 Nov 7.
A cyclical corticosteroid-cyclophosphamide regimen is recommended for patients with primary membranous nephropathy at high risk of progression. We hypothesized that sequential therapy with tacrolimus and rituximab is superior to cyclical alternating treatment with corticosteroids and cyclophosphamide in inducing persistent remission in these patients. This was tested in a randomized, open-label controlled trial of 86 patients with primary membranous nephropathy and persistent nephrotic syndrome after six-months observation and assigned 43 each to receive six-month cyclical treatment with corticosteroid and cyclophosphamide or sequential treatment with tacrolimus (full-dose for six months and tapering for another three months) and rituximab (one gram at month six). The primary outcome was complete or partial remission of nephrotic syndrome at 24 months. This composite outcome occurred in 36 patients (83.7%) in the corticosteroid-cyclophosphamide group and in 25 patients (58.1%) in the tacrolimus-rituximab group (relative risk 1.44; 95% confidence interval 1.08 to 1.92). Complete remission at 24 months occurred in 26 patients (60%) in the corticosteroid-cyclophosphamide group and in 11 patients (26%) in the tacrolimus-rituximab group (2.36; 1.34 to 4.16). Anti-PLA2R titers showed a significant decrease in both groups but the proportion of anti-PLA2R-positive patients who achieved immunological response (depletion of anti-PLA2R antibodies) was significantly higher at three and six months in the corticosteroid-cyclophosphamide group (77% and 92%, respectively), as compared to the tacrolimus-rituximab group (45% and 70%, respectively). Relapses occurred in one patient in the corticosteroid-cyclophosphamide group, and three patients in the tacrolimus-rituximab group. Serious adverse events were similar in both groups. Thus, treatment with corticosteroid-cyclophosphamide induced remission in a significantly greater number of patients with primary membranous nephropathy than tacrolimus-rituximab.
一种环磷酰胺-环孢菌素方案被推荐用于有进展高风险的原发性膜性肾病患者。我们假设，他克莫司和利妥昔单抗序贯治疗优于皮质类固醇和环磷酰胺的周期性交替治疗，可诱导这些患者持续缓解。这在一项针对 86 例原发性膜性肾病和持续肾病综合征患者的随机、开放性对照试验中进行了测试，这些患者在观察 6 个月后被平均分配到环磷酰胺和皮质类固醇组（6 个月的周期性治疗）或他克莫司-利妥昔单抗组（6 个月时全剂量治疗，然后再持续 3 个月减剂量治疗）。主要终点是在 24 个月时肾病综合征完全或部分缓解。在皮质类固醇-环磷酰胺组，有 36 例（83.7%）患者达到了完全或部分缓解，而在他克莫司-利妥昔单抗组，有 25 例（58.1%）患者达到了完全或部分缓解（相对风险 1.44；95%置信区间 1.08 至 1.92）。在皮质类固醇-环磷酰胺组，有 26 例（60%）患者在 24 个月时达到完全缓解，而在他克莫司-利妥昔单抗组，有 11 例（26%）患者达到完全缓解（2.36；1.34 至 4.16）。两组的抗 PLA2R 滴度均显著下降，但在皮质类固醇-环磷酰胺组，达到免疫反应（抗 PLA2R 抗体耗竭）的抗 PLA2R 阳性患者比例在 3 个月和 6 个月时明显更高（分别为 77%和 92%），而在他克莫司-利妥昔单抗组，这一比例分别为 45%和 70%。在皮质类固醇-环磷酰胺组有 1 例患者复发，在他克莫司-利妥昔单抗组有 3 例患者复发。两组的严重不良事件相似。因此，与他克莫司-利妥昔单抗相比，皮质类固醇-环磷酰胺治疗可显著诱导更多原发性膜性肾病患者缓解。
