Observational study of spinal muscular atrophy type I and implications for clinical trials
Observational study of spinal muscular atrophy type I and implications for clinical trials
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DOI：
10.1212/wnl.0000000000000741
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发表时间：
2014-08-26
期刊：
影响因子：
9.9
通讯作者：
De Vivo, Darryl C.
中科院分区：
文献类型：
--
作者：
Finkel, Richard S.;McDermott, Michael P.;De Vivo, Darryl C.
目的：前瞻性队列研究，以表征的临床特征和过程中的脊髓性肌萎缩症I型（SMA-I）。方法：患者在3个研究地点入组，并随访长达36个月的系列临床，运动功能，实验室，和电生理结果评估。干预措施由已公布的护理标准指南确定。姑息治疗选项offered.Results：三十四个54个符合条件的受试者与SMA-I（63%）入组，其中50%完成了至少12个月的随访。达到死亡或需要至少16小时/天通气支持的联合终点时的中位年龄为13.5个月（四分位距8.1-22.0个月）。营养支持的需求先于通气支持。在3个月前和3个月后出现症状的SMA-I受试者中，达到联合终点时的年龄分布相似（p = 0. 58）。具有2个SMN 2拷贝与具有3个拷贝的发病率和死亡率更高相关。基线电生理测量表明大量运动神经元丢失。相比之下，失去坐姿能力的SMA-II受试者（n=10）的运动功能、运动单位数量估计和复合运动动作电位更高，生存期更长，需要进食或通气支持的年龄更晚。费城儿童医院婴儿神经肌肉疾病运动功能量表测试的平均下降率为1.27分/年（95%置信区间为0.21-2.33，p = 0.02）。结论：SMA-I婴儿可以有效地纳入并保留在12个月的自然史研究，直到大多数达到联合终点。这些结果数据可用于临床试验设计。
Objectives: Prospective cohort study to characterize the clinical features and course of spinal muscular atrophy type I (SMA-I).Methods: Patients were enrolled at 3 study sites and followed for up to 36 months with serial clinical, motor function, laboratory, and electrophysiologic outcome assessments. Intervention was determined by published standard of care guidelines. Palliative care options were offered.Results: Thirty-four of 54 eligible subjects with SMA-I (63%) enrolled and 50% of these completed at least 12 months of follow-up. The median age at reaching the combined endpoint of death or requiring at least 16 hours/day of ventilation support was 13.5 months (interquartile range 8.1-22.0 months). Requirement for nutritional support preceded that for ventilation support. The distribution of age at reaching the combined endpoint was similar for subjects with SMA-I who had symptom onset before 3 months and after 3 months of age (p = 0.58). Having 2 SMN2 copies was associated with greater morbidity and mortality than having 3 copies. Baseline electrophysiologic measures indicated substantial motor neuron loss. By comparison, subjects with SMA-II who lost sitting ability (n=10) had higher motor function, motor unit number estimate and compound motor action potential, longer survival, and later age when feeding or ventilation support was required. The mean rate of decline in The Children's Hospital of Philadelphia Infant Test for Neuromuscular Disorders motor function scale was 1.27 points/year (95% confidence interval 0.21-2.33, p = 0.02).Conclusions: Infants with SMA-I can be effectively enrolled and retained in a 12-month natural history study until a majority reach the combined endpoint. These outcome data can be used for clinical trial design.