Fixed- or Controlled-Dose Mycophenolate Mofetil with Standard- or Reduced-Dose Calcineurin Inhibitors: The Opticept Trial
Fixed- or Controlled-Dose Mycophenolate Mofetil with Standard- or Reduced-Dose Calcineurin Inhibitors: The Opticept Trial
复制标题
DOI：
10.1111/j.1600-6143.2009.02668.x
复制
发表时间：
2009-07-01
影响因子：
8.8
通讯作者：
Bloom, R. D.
中科院分区：
文献类型：
--
作者：
Gaston, R.;Kaplan, B.;Bloom, R. D.
霉酚酸酯（MMF）是与环孢素一起开发的固定剂量免疫抑制剂。最近的数据表明，麦考酚酸（MPA）暴露在个人和排斥反应和毒性的临床终点之间的关系。这项为期2年、开放标签、随机、多中心试验在720名肾移植受者中比较了浓度控制的MMF（MMFCC）给药与固定剂量方案的疗效和安全性。患者接受（A）MMFCC和降低水平的钙调磷酸酶抑制剂（MMFCC/CNIRL）;（B）MMFCC和标准水平的CNI（MMFCC/CNISL）;或（C）固定剂量的MMF和CNISL（MMFFD/CNISL）。抗体诱导和类固醇使用根据中心实践。主要终点是1年时A组与C组治疗失败（包括活检证实的急性排斥反应[BPAR]、移植物丢失和死亡）的非劣效性（α = 0.05）。尽管A组的平均CNI谷水平未达到预定目标，但在统计学上低于B和C组（每次比较p < 0.01）。各组的BPAR率（8.5%）均较低。A组治疗失败率低19%（23% vs. 28%，p = 0.18）。A组的MMF剂量最高（p < 0.05），因不良事件而退出的人数最少（p = 0.02）。在80%服用他克莫司（Tac）的受试者中，MPA暴露量较高的受试者排斥反应明显较少（p < 0.001），腹泻与Tac相关，但与MPA水平无关。因此，MMFCC与低剂量CNI的结局不劣于标准CNI暴露和MMFFD，表明MMFCC在CNI保留方案中的潜在效用。
Mycophenolate mofetil (MMF) was developed with cyclosporine as a fixed-dose immunosuppressant. More recent data indicate a relationship between mycophenolic acid (MPA) exposure in individuals and clinical endpoints of rejection and toxicity. This 2-year, open-label, randomized, multicenter trial compared the efficacy and safety of concentration-controlled MMF (MMFCC) dosing with a fixed-dose regimen in 720 kidney recipients. Patients received either (A) MMFCC and reduced-level calcineurin inhibitor (MMFCC/CNIRL); (B) MMFCC and standard-level CNI (MMFCC/CNISL); or (C) fixed-dose MMF and CNISL (MMFFD/CNISL). Antibody induction and steroid use were according to center practice. The primary endpoint was noninferiority (alpha = 0.05) of group A versus group C for treatment failure (including biopsy-proven acute rejection [BPAR], graft loss and death) at 1 year. Although mean CNI trough levels in group A did not reach the prespecified targets, they were statistically lower than those in groups B and C (p < 0.01 for each comparison). BPAR rates (8.5%) were low across groups. Group A had 19% fewer treatment failures (23% vs. 28%, p = 0.18). MMF doses were highest (p < 0.05), with withdrawals for adverse events the fewest (p = 0.02), in group A. Of the 80% of subjects taking tacrolimus (Tac), those with higher MPA exposure had significantly less rejection (p < 0.001) and diarrhea correlated with Tac, but not with MPA levels. Thus, MMFCC with low-dose CNI resulted in outcomes not inferior to those with standard CNI exposure and MMFFD, indicating potential utility of MMFCC in CNI-sparing regimens.