Efficacy and safety of deflazacort vs prednisone and placebo for Duchenne muscular dystrophy
Efficacy and safety of deflazacort vs prednisone and placebo for Duchenne muscular dystrophy
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DOI：
10.1212/wnl.0000000000003217
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发表时间：
2016-11-15
期刊：
影响因子：
9.9
通讯作者：
Meyer, James M.
中科院分区：
文献类型：
--
作者：
Griggs, Robert C.;Miller, J. Phillip;Meyer, James M.
目的：评价地沙唑（DFZ）和强的松（PRED）与安慰剂治疗杜氏肌营养不良（DMD）的安全性和有效性。方法：这项III期、随机、安慰剂对照、多中心研究评估了196名5-15岁患有DMD的男孩在52周内的肌肉力量。在第一阶段，参与者被随机分配接受DFZ 0.9 mg/kg/d、DFZ 1.2 mg/kg/d、PRED 0.75 mg/kg/d或安慰剂治疗12周。在第二阶段，安慰剂参与者被随机分配到三个积极治疗组中的一个。最初被分配到积极治疗组的参与者继续接受额外的40周治疗。主要疗效终点是与安慰剂相比，肌肉力量从基线到第12周的平均变化。这项研究于1995年完成。结果：所有治疗组（DFZ 0.9 mg/kg/d, DFZ 1.2 mg/kg/d, PRED 0.75 mg/kg/d）在12周时与安慰剂相比，肌肉力量均有显著改善。在12周时，服用PRED的受试者体重增加明显多于安慰剂或两种剂量的DFZ；在52周时，服用PRED的参与者比服用两种DFZ的参与者体重增加明显更多。在所有3个积极治疗组中，最常见的不良事件是库欣样样外观、红斑、多毛、体重增加、头痛和鼻咽炎。结论：治疗12周后，与安慰剂相比，PRED和两种剂量的DFZ均能改善肌肉力量。与PRED相比，Deflazacort与体重增加的关系更小。证据分类：本研究提供了一级证据，表明对于患有DMD的男孩，每天使用DFZ和PRED在12周内有效地保持肌肉力量。
Objective: To assess safety and efficacy of deflazacort (DFZ) and prednisone (PRED) vs placebo in Duchenne muscular dystrophy (DMD).Methods: This phase III, double-blind, randomized, placebo-controlled, multicenter study evaluated muscle strength among 196 boys aged 5-15 years with DMD during a 52-week period. In phase 1, participants were randomly assigned to receive treatment with DFZ 0.9 mg/kg/d, DFZ 1.2 mg/kg/d, PRED 0.75 mg/kg/d, or placebo for 12 weeks. In phase 2, placebo participants were randomly assigned to 1 of the 3 active treatment groups. Participants originally assigned to an active treatment continued that treatment for an additional 40 weeks. The primary efficacy endpoint was average change in muscle strength from baseline to week 12 compared with placebo. The study was completed in 1995.Results: All treatment groups (DFZ 0.9 mg/kg/d, DFZ 1.2 mg/kg/d, and PRED 0.75 mg/kg/d) demonstrated significant improvement in muscle strength compared with placebo at 12 weeks. Participants taking PRED had significantly more weight gain than placebo or both doses of DFZ at 12 weeks; at 52 weeks, participants taking PRED had significantly more weight gain than both DFZ doses. The most frequent adverse events in all 3 active treatment arms were Cushingoid appearance, erythema, hirsutism, increased weight, headache, and nasopharyngitis.Conclusions: After 12 weeks of treatment, PRED and both doses of DFZ improved muscle strength compared with placebo. Deflazacort was associated with less weight gain than PRED. Classification of evidence: This study provides Class I evidence that for boys with DMD, daily use of either DFZ and PRED is effective in preserving muscle strength over a 12-week period.