Mycophenolate mofetil for steroid-dependent nephrotic syndrome: a phase II Bayesian trial
Mycophenolate mofetil for steroid-dependent nephrotic syndrome: a phase II Bayesian trial
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DOI：
10.1007/s00467-011-2006-7
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发表时间：
2012-03-01
影响因子：
3
通讯作者：
Loirat, Chantal
中科院分区：
文献类型：
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作者：
Baudouin, Veronique;Alberti, Corinne;Loirat, Chantal
霉酚酸酯(MMF)已成为激素依赖型肾病综合征(SDNS)的一种新的治疗选择。我们在患有SDNS的儿童中进行了MMF的第二阶段贝叶斯试验。第二阶段试验，通常是单臂研究，调查新治疗的效果。标准的Fleming程序依赖于观察结果(试验期间的复发率)，而贝叶斯方法将观察结果与先前信息(根据先前研究和临床经验的预期复发率)相结合。所有患者都被要求事先接受过烷化剂治疗。其中67%的人也接受了左旋咪唑治疗。患者接受MMF(1,200 mg/m(2)/天)和泼尼松的治疗[隔日剂量(E.O.D)在3个月减少到MMF前剂量的50%，6个月减少到25%]。24名儿童(平均年龄6.0岁，2.8-14.4岁)参加了这项研究，其中23人完成了研究。贝叶斯分析表明，增加四名患者不会改变结果的意义，允许停止包含。4名患者在前6个月复发(估计概率为17.6%，95%可信区间：5.4-35.0%)，2名患者分别在8个月和11.5个月复发。在前6个月无复发的19例患者中，泼尼松维持剂量的中位数(Q1-Q3)从25(10-44)mg/m(2)降至9(7.5-11.2)mg/m(2)E.O.D(p<；0.001)，累积剂量从459(382-689)降至264(196-306)mg/m(2)/月(p<；0.001)。MMF前期患者的特征和MMF药代动力学在有无复发的患者之间没有差别。MMF可降低SDNS儿童的复发率和类固醇剂量，应在环孢素A和环磷酰胺之前提出。
Mycophenolate mofetil (MMF) has emerged as a new therapeutic option in steroid-dependent nephrotic syndrome (SDNS). We conducted a phase II Bayesian trial of MMF in children with SDNS. Phase II trials, usually single-arm studies, investigate the effect of new treatments. Standard Fleming's procedure relies on observed results (relapse rate during the trial), whereas Bayesian approach combines observed results with prior information (expected relapse rate according to prior studies and clinical experience). All patients were required to have received prior alkylating-agent treatment. Sixty-seven percent of them had also received levamisole. Patients received MMF (1,200 mg/m(2)/day) and prednisone according to a defined schedule [reduction of alternate-day (e.o.d) dose to 50% of pre-MMF dose at 3 months, 25% at 6 months]. Twenty-four children (median age 6.0 years, 2.8-14.4) entered the study and 23 completed it. Bayesian analysis showed that adding four patients would not change significance of results, allowing stopping inclusions. Four patients relapsed during the first 6 months (estimated probability 17.6%, 95% credibility interval: 5.4-35.0%) and two at months 8 and 11.5. In the 19 patients free of relapse during the first 6 months, median (Q1-Q3) prednisone maintenance dose decreased from 25 (10-44) to 9 (7.5-11.2) mg/m(2) e.o.d (p < 0.001) and cumulative dose from 459 (382-689) to 264 (196-306) mg/m(2)/month (p < 0.001) before and on MMF respectively. Pre-MMF patient characteristics and MMF pharmacokinetics did not differ between patients with or without relapse. MMF reduces relapse rate and steroid dose in children with SDNS and should be proposed before cyclosporine and cyclophosphamide.