高剂量的努辛森治疗脊柱肌肉缩:一个第三阶段随机试验
Richard S Finkel1, Thomas O Crawford2, Eugenio Mercuri3,4
1St. Jude Children's Research Hospital, Memphis, TN, USA. richard.finkel@stjude.org.
Nature medicine
|February 3, 2026
概括
高剂量的努辛森显著改善了脊柱肌肉缩 (SMA) 患者的结局,正如DEVOTE试验所示. 这种较高的剂量显示出有利的安全性,类似于标准剂量,支持其临床益处.
科学领域:
- 神经学 神经学
- 遗传学 遗传学 是一个
- 临床试验 临床试验
背景情况:
- 脊椎肌肉缩 (SMA) 是一种罕见的遗传神经肌肉疾病.
- 目前的疾病修饰疗法,包括nusinersen,提供好处,但可能不能完全解决所有临床表现.
- 需要探索更高剂量的疗法来提高潜在的疗效.
研究的目的:
- 评估高剂量努辛森治疗方案在SMA患者中的疗效和安全性.
- 评估高剂量努辛森能否快速减缓神经退行并改善患者的治疗结果.
- 在一项随机对照试验中,比较高剂量nusinersen与标准剂量和安慰剂的影响.
主要方法:
- 全球,二/三阶段的DEVOTE试验 (NCT04089566) 包括未接受过治疗的SMA患者,随机分配为高剂量 (50/28 mg) 或标准剂量 (12/12 mg) nusinersen.
- 部分B侧重于未经治疗的婴儿,主要终点是费城儿童医院神经肌肉疾病婴儿测试 (CHOP-INTEND) 得分的6个月变化.
- 与接受虚假治疗的ENDEAR试验的匹配参与者进行了比较.
主要成果:
- DEVOTE试验达到其主要终点,在接受高剂量努辛森 (+15.1分) 的患者中,与假治疗对照 (-11.1分) 相比,在183天内CHOP-INTEND得分显著改善.
- 高剂量组和假药组之间的CHOP-INTEND得分变化差异为26.19 (95% CI:20.7至31.74;P < 0.0001).
- 高剂量 (50/28毫克) 努辛森疗法的安全概况与标准12/12毫克剂量相当,表明耐受性良好.
结论:
- 高剂量的nusinersen在改善SMA婴儿的运动功能方面表现出显著的有效性.
- 高剂量nusinersen的安全性概况与标准剂量相似,这表明它被很好地容忍.
- 这些发现支持使用高剂量的努辛森作为SMA患者有益的治疗选择.
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