Elsevier

The Journal of Pediatrics

Volume 219, April 2020, Pages 223-228.e4
The Journal of Pediatrics

Original Article
Respiratory Needs in Patients with Type 1 Spinal Muscular Atrophy Treated with Nusinersen

https://doi.org/10.1016/j.jpeds.2019.12.047Get rights and content

Objective

To evaluate the effects of nusinersen on respiratory function of patients with type 1 spinal muscular atrophy.

Study design

Observational, longitudinal cohort study. We collected respiratory data from 118 children with type 1 spinal muscular atrophy and differing pulmonary requirements and conducted a semistructured qualitative interview among a subsample of caregivers at baseline, 6 months, and 10 months after the first nusinersen treatment. Patients were stratified according to ventilation modalities and age at study entry.

Results

Most patients in our cohort remained stable (84/109 = 77%). More than 80% of the children treated before age 2 years survived, in contrast to the lower survival reported in natural history studies, and did so without tracheostomy or noninvasive ventilation (NIV) ≥16 hours. In those less than 2 years old, only 3 patients shifted from NIV ≤10 hours to NIV >10 hours, and the other 3 reduced the hours of NIV required. Most of the older patients remained stable; this included not only those on tracheostomy or NIV >10 hours but also 75% of those on NIV ≤10 hours.

Conclusions

Our results suggest that nusinersen may produce some improvement in the progression of respiratory impairment, both in terms of survival and need for respiratory support ≥16 hours, especially before the age of 2 years.

Section snippets

Methods

All the patients with type 1 SMA who participated in the EAP program with nusinersen from baseline to 300 days after first infusion (T300) were included for our analysis. Details of the EAP Italian experience have already been reported.10,14 Intrathecal injections with nusinersen were administered on days 1, 15, 30, 60 (loading doses), and then every 4 months (maintenance doses). Institutional review board approval and parents' consents were obtained at each site. The design of the study and

Results

One hundred eighteen patients had their first infusion successfully performed at baseline (median age 42.8 months; IQR 11.0-102.8 months). Four patients died, and another 6 withdrew their participation before the tenth month, either because of difficulties related to the administration procedure, or because the effects of treatment were not as evident as expected. Five had to be re-directed to local centers in Italy for the treatment and were, therefore, considered lost to follow-up because it

Discussion

Longitudinal natural history data on respiratory function in type 1 SMA are scanty, as until recently most studies focused on survival or time to respiratory event (ie, tracheostomy or ventilation >16 hours). In the last decade, 2 natural history studies, reflecting data collected after care recommendations had become available,17 showed limited survival in the first 2 years of life.5,6,18 Only a few studies reported respiratory data, especially in cohorts including older patients with type 1

References (20)

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  • Evaluation of real-life outcome data of patients with spinal muscular atrophy treated with nusinersen in Switzerland

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    Tube feeding and ventilatory support became necessary at age of 8–20 months, associated with a respiratory infection in all. In our cohort, we did not see a correlation between motor response and the need for ventilatory or feeding support, which is in line with previous reports [38,40]. Patients continued to show improvements with acquisition of a stable sit or the ability to stand with assistance.

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V.S., M.P., E.B., and E.M. serve as scientific consultants for Biogen on Medical Advisory Boards. The other authors declare no conflicts of interest.

Contributed equally.

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