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首页> 外文期刊>Lancet Neurology >Treatment of Duchenne muscular dystrophy with ciclosporin A: a randomised, double-blind, placebo-controlled multicentre trial
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Treatment of Duchenne muscular dystrophy with ciclosporin A: a randomised, double-blind, placebo-controlled multicentre trial

机译：环孢素A治疗Duchenne型肌营养不良症：一项随机，双盲，安慰剂对照的多中心试验

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BACKGROUND: Duchenne muscular dystrophy is a rare X-linked progressive disease characterised by loss of ambulation at about age 10 years, with death in early adulthood due to respiratory and cardiac insufficiency. Steroids are effective at slowing the progression of muscle weakness; however, their use is limited by side-effects, prompting the search for alternatives. We assessed the effect of ciclosporin A as monotherapy and in combination with intermittent prednisone for the treatment of ambulant patients with this disorder. METHODS: Our study was a parallel-group, placebo-controlled, double-blind, multicentre trial at trial sites of the German muscular dystrophy network, MD-NET, over 36 months. Ambulant patients with Duchenne muscular dystrophy who were aged 5 years or older were randomly assigned to receive either ciclosporin A (3·5-4·0 mg/kg per day) or matching placebo. Allocation was done centrally with computer-generated random numbers. Patients and investigators were masked to the allocated treatment. After 3 months of treatment, both groups were also given intermittent prednisone for a further 12 months (0·75 mg/kg, alternating 10 days on with 10 days off). All patients who received at least one dose of study drug or placebo were included in the primary analysis. The primary outcome measure was manual muscle strength measured on the Medical Research Council (MRC) scale. This trial is registered with the German clinical trial register DRKS, number DRKS00000445. FINDINGS: 77 patients were randomly assigned to the ciclosporin A group and 76 to the placebo group; 73 patients on ciclosporin A and 73 on placebo received at least one dose and were available for efficacy analyses. 3 months of treatment with ciclosporin A alone did not show any significant improvement in primary outcome measures (mean change in the proportion of a possible total MRC score [%MRC] was -2·6 [SD 6·0] for patients on ciclosporin A and -0·8 [4·9] for patients on placebo; adjusted group difference estimate -0·88, 97·5% CI -2·6 to 0·9; p=0·26). The combination of ciclosporin A with intermittent steroids was not better than intermittent steroids alone over 12 months (mean change in %MRC was 0·7 [7·1] for patients on ciclosporin A and -0·3 [7·9] for patients on placebo; adjusted group difference estimate -0·85, -3·6 to 1·9; p=0·48). Numbers of adverse events (75 in patients on ciclosporin A and 74 on placebo) and serious adverse events (four with ciclosporin A and four with placebo) did not differ significantly between groups. INTERPRETATION: Ciclosporin A alone or in combination with intermittent prednisone does not improve muscle strength or functional abilities in ambulant boys with Duchenne muscular dystrophy, but is safe and well tolerated. FUNDING: German Federal Ministry of Education and Research, Action Benni and co eV, Novartis Pharma AG, and Deutsche Gesellschaft für Muskelkranke eV.
机译：背景：杜氏肌营养不良症是一种罕见的X连锁进行性疾病，其特征是在大约10岁时失去活动能力，并由于呼吸和心脏功能不全而在成年早期死亡。类固醇可有效减缓肌肉无力的进展;然而，它们的使用受到副作用的限制，促使人们寻找替代品。我们评估了环孢菌素A作为单药治疗以及与间歇性泼尼松联合用于治疗患有这种疾病的门诊患者的效果。方法：我们的研究是在德国肌肉营养不良网络MD-NET的试验地点进行的一项平行组，安慰剂对照，双盲，多中心试验，历时36个月。 5岁或以上的患有Duchenne肌营养不良症的救护车患者被随机分配接受环孢菌素A（每天3·5-4·0 mg / kg）或匹配的安慰剂。使用计算机生成的随机数集中进行分配。患者和研究人员被掩盖了分配的治疗方法。在治疗3个月后，两组还分别接受了间歇性泼尼松治疗12个月（0·75毫克/千克，交替使用10天和停用10天）。所有接受至少一剂研究药物或安慰剂的患者都包括在主要分析中。主要结果指标是按照医学研究理事会（MRC）量表测量的手动肌肉力量。该试验已在德国临床试验注册机构DRKS中注册，编号为DRKS00000445。结果：将77例患者随机分为环孢素A组和76例安慰剂组。 73名使用环孢菌素A的患者和73名使用安慰剂的患者接受了至少一剂，可用于疗效分析。单独使用环孢菌素A 3个月的治疗未显示主要结局指标有任何明显改善（使用环孢菌素A的患者，可能的总MRC分数[％MRC]的比例平均变化为-2·6 [SD 6·0]安慰剂组患者为-0·8 [4·9];调整组差异估计为-0·88、97·5％CI -2·6至0·9; p = 0·26）。在12个月内，环孢素A与间歇性类固醇的联合治疗并不比单独使用间歇性类固醇好（对于环孢菌素A患者，％MRC的平均变化为0·7 [7·1]，患者为-0·3 [7·9]在安慰剂上;调整组差异估计-0·85，-3·6至1·9; p = 0·48）。两组之间的不良事件数量（使用环孢菌素A的患者为75例，使用安慰剂的患者为74）和严重不良事件（使用环孢菌素A的患者为4个，使用安慰剂的患者为4个）之间没有显着差异。解释：环孢菌素A单独或与间歇性泼尼松联合使用不能改善患有杜氏肌营养不良症的流动男孩的肌肉力量或功能，但安全且耐受性良好。资金：德国联邦教育和研究部，Action Benni及其合作伙伴，诺华制药股份公司和Deutsche GesellschaftfürMuskelkranke eV。

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