One-year Results of the Effects of Rituximab on Acute Antibody-Mediated Rejection in Renal Transplantation: RITUX ERAH, a Multicenter Double-blind Randomized Placebo-controlled Trial
One-year Results of the Effects of Rituximab on Acute Antibody-Mediated Rejection in Renal Transplantation: RITUX ERAH, a Multicenter Double-blind Randomized Placebo-controlled Trial
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DOI：
10.1097/tp.0000000000000958
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发表时间：
2016-02-01
期刊：
影响因子：
6.2
通讯作者：
Lebranchu, Yvon
中科院分区：
文献类型：
--
作者：
Sautenet, Benedicte;Blancho, Gilles;Lebranchu, Yvon
背景急性抗体介导的排斥反应（AMR）的治疗是基于血浆置换（PE），IVIg，皮质类固醇（CS）和利妥昔单抗的组合，但在缺乏随机试验的情况下，利妥昔单抗的位置并不明确。方法.在这项III期、多中心、双盲、安慰剂对照试验中，我们随机分配活检证实的AMR患者在第5天接受利妥昔单抗（375 mg/m（2））或安慰剂。所有患者均接受PE、IVIg和CS治疗。主要终点是第12天移植物丢失或肾功能无改善的复合终点。结果在纳入的38例患者中，在1年时，未发生死亡，但每组均发生1例移植物丢失。利妥昔单抗组和安慰剂组的主要终点频率分别为52.6%（10/19）和57.9%（11/19）（P = 0.744）。两组患者的肾功能均在第12天得到改善，在1、3、6和12个月时血清肌酐水平和蛋白尿无差异。两组之间的利妥昔单抗补充给药和IVIg和PE治疗总数没有差异。两组在1个月和6个月时AMR和Banff评分的组织学特征均有所改善，组间无显著差异，但利妥昔单抗组有优势。两组在第12天就显示出供体特异性抗体的平均荧光强度降低，它们之间没有显著差异，但在12个月时利妥昔单抗组的趋势有利。结论.随访1年后，我们没有观察到利妥昔单抗对接受PE、IVIg和CS治疗AMR的患者的额外影响。然而，我们的研究动力不足，组间的重要差异可能被遗漏。需要补充试验和长期随访。
Background. Treatment of acute antibody-mediated rejection (AMR) is based on a combination of plasma exchange (PE), IVIg, corticosteroids (CS), and rituximab, but the place of rituximab is not clearly specified in the absence of randomized trials. Methods. In this phase III, multicenter, double-blind, placebo-controlled trial, we randomly assigned patients with biopsy-proven AMR to receive rituximab (375 mg/m(2)) or placebo at day 5. All patients received PE, IVIg, and CS. The primary endpoint was a composite of graft loss or no improvement in renal function at day 12. Results. Among the 38 patients included, at 1 year, no deaths occurred, but 1 graft loss occurred in each group. The primary endpoint frequency was 52.6% (10/19) and 57.9% (11/19) in the rituximab and placebo groups, respectively (P = 0.744). Renal function improved in both groups, as soon as day 12 with no difference in serumcreatinine level and proteinuria at 1, 3, 6, and 12 months. Supplementary administration of rituximab and total number of IVIg and PE treatments did not differ between the 2 groups. Both groups showed improved histological features of AMR and Banff scores at 1 and 6 months, with no significant difference between groups but with a trend in favor of the rituximab group. Both groups showed decreased mean fluorescence intensity of donor-specific antibodies as soon as day 12, with no significant difference between them but with a trend in favor of the rituximab group at 12 months. Conclusions. After 1 year of follow-up, we observed no additional effect of rituximab in patients receiving PE, IVIg, and CS for AMR. Nevertheless, our study was underpowered and important differences between groups may have been missed. Complementary trials with long-term follow-up are needed.