Chacko Archana, Sly Peter D, Ware Robert S, Dyer Brett, Deegan Sean, Thomas Nicole, Gauld Leanne M
Centre for Child Health Research, University of Queensland, Brisbane, Australia.
Centre for Child Health Research, University of Queensland, Brisbane, Australia; Queensland Respiratory and Sleep Department, Queensland Children's Hospital, Brisbane, Australia.
Sleep Med. 2025 May;129:354-362. doi: 10.1016/j.sleep.2025.02.034. Epub 2025 Feb 25.
To establish whether the initial positive effect of nusinersen (NUS) on respiratory outcomes in the first year of treatment was maintained in children with Spinal Muscular Atrophy (SMA) type 2 and to further define the effect on children with type 3 treated over 3 years.
A prospective observational study of children with type 2 and 3 beginning NUS in Queensland, Australia between June 2018-December 2020 was undertaken. Investigations conducted included age-appropriate lung function and polysomnography. Lung function data for two-years preceding NUS initiation was retrospectively collected. Change in lung function/polysomnography was assessed using mixed effects linear regression.
24 of 30 children with type 2 and 3 SMA (14 males; 2.6-15.8) were included (type 2 n = 12; type 3 n = 12). No child had respiratory-related admissions during the period of study. For type 2, annual decline in FVC z-score pre-treatment was -0.75 (95 % CI: 1.14, -0.39, p < 0.001), and for the first 3 years on NUS was -0.20 ([95 % CI: 0.33, -0.06, p = 0.01] difference p = 0.008). For type 3 minimal change was seen: pre-NUS and post FVC z-scores -0.20 (95 % CI: 1.00, 0.61 p = 0.05) and -0.46 (95 % CI: 0.88, -0.04 p = 0.40) respectively (difference p = 0.46). Mean change in total apnoea-hypopnoea indices (total AHI) in type 2 tended to reduce -1.75 (95 % CI: 4.95-0.9, p = 0.24); type 3 appeared to remain stable (-0.39 [95 % CI: 1.1-0.33, p = 0.28). One child with type 2 ceased NIV due to normalisation of total AHI and gas exchange.
Nusinersen lung function (FVC-z-scores) stability seen in the first year was maintained over 3 years and the total AHI tended to improve in type 2, but the long-term effects in type 3 are less clear.
确定在治疗的第一年，诺西那生钠（NUS）对2型脊髓性肌萎缩症（SMA）患儿呼吸结局的初始积极影响是否得以维持，并进一步明确其对接受3年以上治疗的3型患儿的影响。
对2018年6月至2020年12月在澳大利亚昆士兰州开始使用NUS的2型和3型患儿进行前瞻性观察研究。进行的调查包括适合年龄的肺功能检查和多导睡眠图检查。回顾性收集NUS开始使用前两年的肺功能数据。使用混合效应线性回归评估肺功能/多导睡眠图的变化。
纳入了30名2型和3型SMA患儿中的24名（14名男性；年龄2.6 - 15.8岁）（2型12名；3型12名）。研究期间没有患儿因呼吸相关原因入院。对于2型患儿，治疗前FVC z评分的年下降率为-0.75（95%CI：1.14，-0.39，p < 0.001），使用NUS的前3年为-0.20（[95%CI：0.33，-0.06，p = 0.01]，差异p = 0.008）。对于3型患儿，变化极小：使用NUS前和使用后FVC z评分分别为-0.20（95%CI：1.00，0.61，p = 0.05）和-0.46（95%CI：0.88，-0.04，p = 0.40）（差异p = 0.46）。2型患儿的总呼吸暂停低通气指数（总AHI）平均变化倾向于降低-1.75（95%CI：4.95 - 0.9，p = 0.24）；3型患儿似乎保持稳定（-0.39 [95%CI：1.1 - 0.33，p = 0.28]）。一名2型患儿因总AHI和气体交换恢复正常而停止使用无创通气。
在第一年观察到的诺西那生钠对肺功能（FVC - z评分）的稳定性在3年中得以维持，2型患儿的总AHI倾向于改善，但3型患儿的长期影响尚不清楚。
