Differential respiratory function response in paediatric spinal muscular atrophy types 2 and 3 treated with nusinersen over 3 years

Abstract

Aim

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.

Methods

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.

Results

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.

Conclusion

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.