Efficacy and Safety of Rituximab in Patients With Active Proliferative Lupus Nephritis The Lupus Nephritis Assessment With Rituximab Study
Efficacy and Safety of Rituximab in Patients With Active Proliferative Lupus Nephritis The Lupus Nephritis Assessment With Rituximab Study
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DOI：
10.1002/art.34359
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发表时间：
2012-04-01
影响因子：
--
通讯作者：
Appel, Gerald
中科院分区：
文献类型：
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作者：
Rovin, Brad H.;Furie, Richard;Appel, Gerald
Objective.在一项随机、双盲、安慰剂对照的III期临床试验中，评价利妥昔单抗联合霉酚酸酯（MMF）和皮质类固醇治疗狼疮性肾炎的疗效和安全性。III类或IV类狼疮性肾炎患者（n = 144）按1：1的比例随机接受利妥昔单抗（1，000 mg）或安慰剂治疗，治疗时间分别为第1、15、168和182天。主要终点为第52周时的肾脏反应状态。72例患者中有71例患者的外周血CD 19 + B细胞被利妥昔单抗清除。72例接受安慰剂治疗的患者的总体（完全和部分）肾脏缓解率为45.8%，72例接受利妥昔单抗治疗的患者为56.9%（P = 0.18）;部分缓解占差异的大部分。主要终点（利妥昔单抗的上级应答率）未达到。至第52周，8例安慰剂治疗患者和0例利妥昔单抗治疗患者需要环磷酰胺补救治疗。在利妥昔单抗治疗的患者中观察到血清补体C3、C4和抗双链DNA（抗dsDNA）水平的统计学显著改善。在两个治疗组中，抗dsDNA水平的降低大于中位降低与蛋白尿减少相关。两组中严重不良事件（包括感染）的发生率相似。利妥昔单抗组中性粒细胞减少、白细胞减少和低血压的发生率更高。结论。虽然利妥昔单抗治疗导致更多的应答者和抗dsDNA和C3/C4水平的更大降低，但治疗1年后并没有改善临床结局。利妥昔单抗与MMF和皮质类固醇联合用药未产生任何新的或非预期的安全性信号。
Objective. To evaluate the efficacy and safety of rituximab in a randomized, double-blind, placebocontrolled phase III trial in patients with lupus nephritis treated concomitantly with mycophenolate mofetil (MMF) and corticosteroids.Methods. Patients (n = 144) with class III or class IV lupus nephritis were randomized 1: 1 to receive rituximab (1,000 mg) or placebo on days 1, 15, 168, and 182. The primary end point was renal response status at week 52.Results. Rituximab depleted peripheral CD19+ B cells in 71 of 72 patients. The overall (complete and partial) renal response rates were 45.8% among the 72 patients receiving placebo and 56.9% among the 72 patients receiving rituximab (P = 0.18); partial responses accounted for most of the difference. The primary end point (superior response rate with rituximab) was not achieved. Eight placebo-treated patients and no rituximab-treated patients required cyclophosphamide rescue therapy through week 52. Statistically significant improvements in serum complement C3, C4, and anti-double-stranded DNA (anti-dsDNA) levels were observed among patients treated with rituximab. In both treatment groups, a reduction in anti-dsDNA levels greater than the median reduction was associated with reduced proteinuria. The rates of serious adverse events, including infections, were similar in both groups. Neutropenia, leukopenia, and hypotension occurred more frequently in the rituximab group.Conclusion. Although rituximab therapy led to more responders and greater reductions in anti-dsDNA and C3/C4 levels, it did not improve clinical outcomes after 1 year of treatment. The combination of rituximab with MMF and corticosteroids did not result in any new or unexpected safety signals.