Center for Genomic Medicine and Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.
Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA.
J Neuromuscul Dis. 2020;7(3):257-268. doi: 10.3233/JND-190453.
The impact of nusinersen therapy on outcomes in adults with Spinal Muscular Atrophy (SMA) remains uncertain.
To demonstrate whether nusinersen therapy, at currently prescribed doses, can stabilize or improve motor function in adults with SMA using existing outcome measures.
A single-center prospective cohort study of 6 adults with SMA type 3, with inclusion/exclusion criteria intended to optimize the ability to demonstrate change using established outcome measures. Primary outcomes were the Hammersmith Functional Motor Scale-Expanded (HFMSE) and the Revised Upper Limb Measure (RULM). Secondary outcomes were the PedsQL Fatigue scale, the SMA Functional Rating Scale (SMAFRS), and the 6-minute and 10-meter walk tests (6 MWT and 10 MWT). Estimates of change in HFMSE and RULM mean scores across visits were calculated using a linear mixed effects model. Change from baseline was used for other outcome measures.
HFMSE and RULM scores over 12 months were stable or improved in all participants, with a mean increase of 2 points in each. Other measures showed high intra-individual variability. Adverse events related to the primary diagnosis, including injury and infection, significantly impacted the ability to reliably perform walk tests in the four ambulatory participants.
HFMSE and RULM show potential as responsive outcome measures of motor function in ambulatory and non-ambulatory adults with SMA type 3. A time-dependent accrual of benefit of nusinersen on motor function was apparent in this cohort. More sensitive alternative measures of quality of life, fatigue, exercise tolerance, stability and ADLs are clearly needed for adults with SMA.
依那西普治疗对成年人脊髓性肌萎缩症（SMA）的疗效仍不确定。
使用现有的疗效评估指标，证明目前规定剂量的依那西普治疗能否稳定或改善成年 SMA 患者的运动功能。
这是一项单中心前瞻性队列研究，纳入了 6 名 SMA 3 型成年患者，纳入/排除标准旨在优化使用既定疗效评估指标来证明疗效的能力。主要结局是 Hammersmith 功能性运动量表扩展版（HFMSE）和修订后的上肢测量量表（RULM）。次要结局是儿科生活质量量表疲劳部分、SMA 功能评定量表（SMAFRS）以及 6 分钟步行试验（6MWT）和 10 米步行试验（10MWT）。使用线性混合效应模型计算各访视点 HFMSE 和 RULM 平均评分的变化估计值。其他结局评估指标则使用基线值进行评估。
所有参与者的 HFMSE 和 RULM 评分在 12 个月内保持稳定或改善，平均各增加 2 分。其他指标的个体内变异性较大。与主要诊断相关的不良事件，包括损伤和感染，显著影响了 4 名可步行参与者进行可靠步行测试的能力。
HFMSE 和 RULM 可能成为反应性运动功能评估指标，用于评估 3 型 SMA 成年患者的运动功能。在本队列中，依那西普治疗对运动功能的获益呈现出时间依赖性增加。对于 SMA 成年患者，显然还需要更敏感的替代生活质量、疲劳、运动耐量、稳定性和日常生活活动评估指标。
