小剂量激素治疗Duchenne型肌营养不良的疗效

Efficacy of Low Dose Corticosteroid Therapy in Duchenne Muscular Dystrophy

目的评估短期应用小剂量糖皮质激素是否具有提高Duchenne型肌营养不良（Duchenne muscular dystrophy,DMD）患儿肌力和运动功能的作用。方法纳入2005年9月至2008年12月北京协和医院明确诊断的5~10岁DMD患儿。试验采取随机、双盲、对照的原则,分为治疗组和对照组。治疗组患儿给予泼尼松0.75 mg/（kg·d）,对照组给予维生素C 0.3 mg/d。治疗时间为3个月,每隔1个月随访1次,随访3个月,评估4次就诊时的肌力、运动功能、肺功能和肌酸激酶。结果共31例DMD患儿纳入研究,其中治疗组17例,对照组14例。对照组患儿4次就诊的平均肌力评分依次为38.2±7.5、37.0±8.0、36.2±7.6、36.6±7.7,治疗组为37.7±6.1、39.1±6.4、40.3±5.9、40.0±5.6,两组治疗1、2、3个月后与治疗前肌力的差值比较,差异均有统计学意义（P=0.024,P=0.000,P=0.002）。对照组4次就诊行走9m的平均时间依次为（7.7±2.5）、（7.6±2.8）、（8.1±2.4）、（7.6±2.8）s,治疗组为（8.5±3.4）、（7.2±3.3）、（7.6±3.1）、（7.1±2.8）s,两组治疗2、3个月后与治疗前行走9 m所用时间的差值比较,差异均有统计学意义（P=0.013,P=0.003）。对照组4次就诊的平均用力肺活量（forced vital capacity,FVC）依次为（1.24±0.28）、（1.13±0.26）、（1.21±0.31）、（1.16±0.26）L,治疗组为（1.14±0.37）、（1.40±0.35）、（1.42±0.36）、（1.52±0.37）L,两组治疗1、2、3个月后与治疗前FVC的差值比较,差异均有统计学意义（P=0.000,P=0.006,P=0.000）。两组治疗1个月后与治疗前的肌酸激酶的差值比较,差异亦有统计学意义（P=0.035）。3个月后治疗组激素不良反应仅表现为体重增加,无其他严重不良反应。结论短期应用小剂量泼尼松治疗DMD可以增加患儿肌力,改善患儿运动及肺功能。

Objective To assess whether low dose corticosteroid could improve muscle strength and motor function in children with Duchenne muscular dystrophy （ DMD） .Methods In this randomized double-blind controlled trial , patients with DMD at the age of 5-10 diagnosed from September 2005 to December 2008 in Peking Union Medical College Hospital were enrolled .The patients were divided into treatment group and control group randomly.The treatment group was given prednisone at a dosage of 0.75 mg/（kg· d） for three months, and the control group was given vitamin C 0.3 mg/d as placebo in the same period .Every patient was followed-up once a month for a total of 4 times, testing muscle strength , motor function （ 9-meter walk test ） , respiratory function [forced vital capacity （FVC）], and serum creatine kinase .Results Thirty-one eligible DMD patients were enrolled, including 17 in the treatment group and 14 in the control group.The mean muscle strength scores of the control group at the 4 clinic visits were 38.2 ±7.5, 37.0 ±8.0, 36.2 ±7.6, and 36.6 ±7.7, while those of the treat-ment group were 37.7 ±6.1, 39.1 ±6.4, 40.3 ±5.9, and 40.0 ±5.6, respectively .The changes in muscle strength scores at 1, 2, 3 months after treatment compared with the scores at diagnosis were all significantly larger in the treatment group than in the control group （P=0.024, P=0.000, P=0.002）.The mean time of 9-meter walk at the 4 visits in the control group were （7.7 ±2.5）, （7.6 ±2.8）, （8.1 ±2.4）, and （7.6 ±2.8） s, and those in the treatment group were （8.5 ±3.4）, （7.2 ±3.3）, （7.6 ±3.1）, and （7.1 ±2.8） s, showing signifi-cantly larger changes of time in the treatment group than in the control group at 2 and 3 months after treatment compared with the time at diagnosis （ P=0.013, P=0.003） .The four mean FVCs in the control group were （1.24 ± 0.28）, （1.13 ±0.26）, （1.21 ±0.31）, and （1.16 ±0.26） L, and the mean FVCs in the treatment group were （1.14 ±0.37）, （1.40 ±0.35）, （1.42 ±0.36）, and （1.52 ±0.37） L, showing significantly larger changes in the treatment group than in the control group at 1, 2, and 3 months after treatment compared with the FVCs at diagnosis （P=0.000, P=0.006, P=0.000）.The decrease of creatine kinase in the treatment group was significantly larger after 1-month treatment than that in the control group （P=0.035）.There were no serious adverse effects in the treatment group except weight gain .Conclusions Short-term application of low dose prednisone in children with DMD can increase muscle strength , improve motor and respiratory functions .