Long-term real-world outcomes of nusinersen treatment in patients with spinal muscular atrophy types I-III.

BACKGROUND

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by mutations or deletions in the survival motor neuron 1 (SMN) gene, with disease severity influenced by SMN2 copy number. Nusinersen, an antisense oligonucleotide therapy, has emerged as an effective treatment option. This study aimed to evaluate the long-term clinical outcomes of nusinersen treatment in SMA patients.

METHODS

Patients with SMA types I-III who received nusinersen between 2017 and 2024 were retrospectively analyzed. SMA type I patients were evaluated using the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND), while types II and III were followed with the Hammersmith Functional Motor Scale-Expanded (HFMSE).

RESULTS

In SMA Type II (n = 11; mean age 17.8 ± 5.7 years), mean HFMSE scores improved from 11.3 ± 16.3 to 14.1 ± 17.4 after fourth dose. In SMA Type III patients (n = 9; mean age 20.2 ± 6.4 years), scores improved from 38.8 ± 22.1 to 43.0 ± 21.8. Linear mixed-effects analysis demonstrated a significant association between cumulative nusinersen dose and improved motor function (p < 0.001). Clinically meaningful improvement was maintained in 75% of patients with SMA types II and III at the final follow-up, whereas outcomes in SMA type I were heterogeneous and could not be interpreted conclusively because of the small sample size, late treatment initiation, and advanced disease severity.

CONCLUSION

Nusinersen was associated with early motor improvement and long-term stabilization, a clinically meaningful outcome given the progressive nature of SMA.