Long-term treatment with eteplirsen in nonambulatory patients with Duchenne muscular dystrophy
Long-term treatment with eteplirsen in nonambulatory patients with Duchenne muscular dystrophy
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DOI：
10.1097/md.0000000000015858
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发表时间：
2019-06-01
期刊：
影响因子：
1.6
通讯作者：
Lowes, Linda P.
中科院分区：
文献类型：
--
作者：
Alfano, Lindsay N.;Charleston, Jay S.;Lowes, Linda P.
本分析旨在描述参与两项临床研究的两名不能行走的杜氏肌营养不良症 (DMD) 患者的结果。 eteplirsen 的两项连续试验（研究 201 和 202）在 DMD 患者（N = 12）中进行，并证实了外显子 51 跳跃的基因突变。在研究 201 中，12 名患者随机接受每周一次、双盲静脉输注 eteplirsen 30 或 50mg/kg 或安慰剂，持续 24 周；然后患者在第 25 至 28 周期间接受开放标签 eteplirsen。所有 12 名患者继续进行开放标签扩展研究 202 并接受 eteplirsen 长期治疗。我们在 240 周的联合治疗中比较了非卧床双胞胎患者与 10 名卧床患者的心脏、肺和上肢功能以及肌营养不良蛋白的产生。 10 名研究患者在两项研究中均保持卧床状态，而同卵双胞胎患者均经历了早期、快速的卧床休息。与其他患者（n = 10；6MWT 范围，341-418m）相比，这对双胞胎患者在基线（6 分钟步行测试 [6MWT]，330 和 256m）时疾病严重程度更高。他们在 240 周内维持了心脏和上肢功能，其结果与保持卧床的患者相似。 eteplirsen 治疗后确认了肌营养不良蛋白的产生。尽管失去了行走能力，但在 eteplirsen 治疗的双胞胎患者中，疾病进展的其他标志物仍然相对稳定，并且与行走患者相似。
This analysis aims to describe the outcomes of two nonambulatory patients with Duchenne muscular dystrophy (DMD) who participated in two clinical studies. The two consecutive trials of eteplirsen (studies 201 and 202) were conducted in patients with DMD (N = 12) and confirmed genetic mutations amenable to exon 51 skipping.In study 201, 12 patients were randomized to receive once-weekly, double-blind intravenous infusions of eteplirsen 30 or 50mg/kg or placebofor 24 weeks; patients then received open-label eteplirsen during weeks 25 through 28. All 12 patients continued onto open-label extension study 202 and received long-term treatment with eteplirsen. We compared cardiac, pulmonary, and upper limb function and dystrophin production in the nonambulatory twin patients versus the 10 ambulatory patients through 240 combined treatment weeks.Ten study patients remained ambulatory through both studies, while the identical twin patients both experienced early, rapid loss of ambulation. The twin patients had greater disease severity at baseline (6-minute walk test [6MWT], 330 and 256m) versus the other patients (n = 10; 6MWT range, 341-418m). They maintained cardiac and upper limb function through combined week 240, with outcomes similar to those of the patients who remained ambulatory. Dystrophin production was confirmed following eteplirsen treatment.Despite the loss of ambulation, other markers of disease progression remained relatively stable in the eteplirsen-treated twin patients and were similar to those of the ambulatory patients.