A Multicenter Randomized Controlled Trial of Rituximab versus Cyclosporine in the Treatment of Idiopathic Membranous Nephropathy (MENTOR)
A Multicenter Randomized Controlled Trial of Rituximab versus Cyclosporine in the Treatment of Idiopathic Membranous Nephropathy (MENTOR)
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DOI：
10.1159/000430849
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发表时间：
2015-01-01
期刊：
影响因子：
2.5
通讯作者：
Cattran, Daniel C.
中科院分区：
文献类型：
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作者：
Fervenza, Fernando C.;Canetta, Pietro A.;Cattran, Daniel C.
背景：特发性膜性肾病仍然是高加索成人肾病综合征的主要原因。环孢素(CsA)免疫抑制治疗在减少蛋白尿方面通常是成功的，但其使用与高复发率相关。利妥昔单抗是一种针对B细胞表面CD20的单抗，能有效地实现特发性膜性肾病患者蛋白尿的完全缓解。然而，利妥昔单抗在诱导和维持这些患者的蛋白尿完全或部分缓解方面是否与CsA一样有效尚不清楚。利妥昔单抗(Mentor)的膜性肾病试验假设，利妥昔单抗靶向B细胞在诱导蛋白尿的长期缓解方面不逊于CsA。方法和设计：特发性膜性肾病、蛋白尿和GT；=5g/24小时，且血管紧张素II阻断至少3个月的患者将被随机分成12个月的治疗期，静脉注射利妥昔单抗1,000毫克(2次输注，相隔14天；如果6个月后蛋白尿大幅减少(等于或>；25%)，重复6个月；或口服CsA 3.5-5 mg/kg/天，持续6个月(如果6个月后蛋白尿显著减少(等于或>；25%)，则继续治疗6个月)。治疗效果将通过随机化后24个月的缓解状态(基于蛋白尿的变化)来评估。将通过收集不良事件数据和评估治疗前和治疗后的实验室数据来评估患者的安全性。在随机化后6个月的访问中，接受CsA或利妥昔单抗随机治疗但尿蛋白没有减少25%(在2周内重复测量证实)的患者将被认为治疗失败并退出研究。讨论：这项研究将首次测试利妥昔单抗在诱导特发性膜性肾病患者蛋白尿的长期缓解(完全或部分)方面是否不逊于CsA。(C)2015年S.Karger AG，巴塞尔
Background: Idiopathic membranous nephropathy remains the leading cause of nephrotic syndrome in Caucasian adults. Immunosuppressive therapy with cyclosporine (CSA) is often successful in reducing proteinuria, but its use is associated with a high relapse rate. Rituximab, a monoclonal antibody that specifically targets CD20 on the surface of B-cells, is effective in achieving a complete remission of proteinuria in patients with idiopathic membranous nephropathy. However, whether rituximab is as effective as CSA in inducing and maintaining complete or partial remission of proteinuria in these patients is unknown. The membranous nephropathy trial of rituximab (MENTOR) hypothesizes that B-cell targeting with rituximab is non-inferior to CSA in inducing long-term remission of proteinuria. Methods and Design: Patients with idiopathic membranous nephropathy, proteinuria >= 5 g/24 h, and a minimum of 3 months of Angiotensin-II blockade will be randomized into a 12-month treatment period with IV rituximab, 1,000 mg (2 infusions, 14 days apart; repeated at 6 months if a substantial reduction in proteinuria (equal to or >25%) is seen at 6 months) or oral CSA 3.5-5 mg/kg/day for 6 months (continued for another 6 months if a substantial reduction in proteinuria (equal to or >25%) is seen at 6 months). The efficacy of treatment will be assessed by the remission status (based on changes in proteinuria) at 24 months from randomization. Patient safety will be assessed via collection of adverse event data and evaluation of pre-and posttreatment laboratory data. At the 6-month post-randomization visit, patients who have been randomized to either CSA or rituximab but who do not have a reduction in proteinuria >= 25% (confirmed on repeat measurements within 2 weeks) will be considered treatment failures and exit the study. Discussion: This study will test for the first time whether treatment with rituximab is non-inferior to CSA in inducing long-term remission (complete or partial) of proteinuria in patients with idiopathic membranous nephropathy. (C) 2015 S. Karger AG, Basel