The long-term efficacy of nusinersen on respiratory functions in children with symptomatic spinal muscular atrophy type 1

Available data regarding the effects of nusinersen on respiratory function in the real-world setting are uncertain. We aimed to evaluate the impact of nusinersen on respiratory outcomes over a follow-up period of up to 72 months in patients with symptomatic spinal muscular atrophy type 1 (SMA type 1).

Respiratory status was defined similarly to previous studies: spontaneous breathing, noninvasive ventilatory support for ≤16 h per day, and permanent assisted ventilation. The planned evaluation time was day 180 (after the fourth dose), day 300 (after the fifth dose), and after the last injection for patients who received nusinersen for 2 years or more.

Our cohort consisted of 32 patients. The mean age at treatment initiation was 6.6 months (range: 2.5-16 months). Twenty-eight of 32 patients were eligible for evaluation after the fourth dose. Twenty-three of 28 patients were eligible for assessment after the fifth dose of nusinersen. Eight patients received nusinersen for 2 years or more (range: 26-72 months). At the last assessment, four patients did not require ventilatory support between the ages of 30 and 81 months. One was successfully weaned from invasive ventilatory support after the tenth dose of nusinersen. The respiratory status of most patients remained stable or worsened following the fourth and fifth doses of nusinersen. There were no significant differences in respiratory status between patients who received nusinersen at 6 months of age or younger and those older than 6 months, after the fourth and fifth doses of nusinersen (p > 0.05).

Improvement in respiratory function in patients treated with nusinersen for 2 years or more is generally not expected in the natural course of the disease. However, in our cohort, patients treated with nusinersen mainly maintained their current respiratory status, and many patients required ventilatory support despite treatment with nusinersen. Therefore, our findings may reflect the limited efficacy of nusinersen in symptomatic patients.