A multicenter trial of mizoribine compared with placebo in children with frequently relapsing nephrotic syndrome
A multicenter trial of mizoribine compared with placebo in children with frequently relapsing nephrotic syndrome
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DOI：
10.1046/j.1523-1755.2000.00168.x
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发表时间：
2000-07-01
影响因子：
19.6
通讯作者：
Maki, S
中科院分区：
文献类型：
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作者：
Yoshioka, K;Ohashi, Y;Maki, S
背景由于皮质类固醇或细胞毒性/免疫抑制剂如环磷酰胺、苯丁酸氮芥和环孢霉素的副作用，其用于治疗频繁复发性肾病综合征（FRNS）的应用受到限制。本研究旨在评价咪唑立宾（一种在日本开发的相对较新的免疫抑制药物）治疗FRNS儿童的疗效和安全性。一项双盲、安慰剂对照、多中心试验在2至19岁的FRNS儿童中进行。复发时，患者接受泼尼松龙治疗。根据动态分配，咪唑立宾或安慰剂同时给予每例患者。泼尼松龙逐渐减量，并在12周内停用。试验药物维持48周。主要终点是复发率（所有患者的复发总数/总治疗天数）。根据意向治疗原则进行分析。对99例咪唑立宾和98例安慰剂治疗的患者进行了主要分析。咪唑立宾组的复发率低于安慰剂组（0.0055 vs. 0.0067，比值0.81，95%CI，0.61 - 1.05，P = 0.12）。两组累积缓解率的风险比为0.79（95%CI，0.57 ~ 1.08）。在由10岁或10岁以下患者组成的亚组中，咪唑立宾亚组（54例患者）和安慰剂亚组（57例患者）之间的复发率比值为0.66（95% CI，0.44至0.94，P = 0.017）。两个亚组之间累积缓解率的风险比为0.56（95%CI，0.37至0.85，P = 0.007）。高尿酸血症是咪唑立宾最常见的不良事件（16%），但为一过性。与安慰剂相比，咪唑立宾显著降低了10岁或以下患者的复发率，延长了缓解期。这种药物可能对FRNS的幼儿有用，他们通常比年龄较大的儿童更容易复发。
Background The use of corticosteroids or cytotoxic/immunosuppressive agents such as cyclophosphamide, chlorambucil, and cyclosporine for the treatment of frequently relapsing nephrotic syndrome (FRNS) is limited because of their adverse effects. This study was conducted to evaluate the efficacy and safety of mizoribine, a relatively new immunosuppressive drug developed in Japan, in children with FRNS.Methods. A double-blind, placebo-controlled, multicenter trial was carried out in children, from 2 to 19 years old, with FRNS. At relapse, patients were treated with prednisolone. According to a dynamic allocation, mizoribine or a placebo was concurrently administered to each patient. Prednisolone was gradually tapered and discontinued within 12 weeks. The test drug was maintained for 48 weeks. The primary end point was the relapse rate (the total number of relapses/the total treatment days for all patients). Analyses were performed according to the intention-to-treat principle.Results. The primary analysis was conducted on 99 mizoribine- and 98 placebo-treated patients. The relapse rate was lower in the mizoribine group than in the placebo group (0.0055 vs. 0.0067 ratio 0.81, 95% CI, 0.61 to 1.05, P = 0.12). The hazard ratio of the cumulative remission rate between the two groups was 0.79 (95% CI, 0.57 to 1.08). In the subgroups consisting of patients 10 years old or younger, the relapse rate ratio between the mizoribine subgroup (54 patients) and the placebo subgroup (57 patients) was 0.66 (95% CI, 0.44 to 0.94, P = 0.017). The hazard ratio of the cumulative remission rate between the two subgroups was 0.56 (95% CI, 0.37 to 0.85, P = 0.007). Hyperuricemia was the most common adverse event with mizoribine (16%), but was transient.Conclusions. Compared with the placebo, mizoribine significantly decreased the relapse rate and prolonged the remission period in the subgroup consisting of patients 10 years old or younger. This drug may be useful in young children with FRNS who generally relapse more frequently than older children.