Effect of nusinersen on motor, respiratory and bulbar function in early-onset spinal muscular atrophy.

5q-associated spinal muscular atrophy (SMA) is a rare neuromuscular disorder with the leading symptom of a proximal muscle weakness. Three different drugs have been approved by EMA and FDA for the treatment of SMA patients, however long-term experience is still scarce. In contrast to clinical trial data with restricted patient populations and short observation periods, we here report real-world evidence on a broad spectrum of patients with early-onset SMA treated with nusinersen focusing on effects regarding motor milestones, and respiratory and bulbar insufficiency during the first years of treatment. Within the SMArtCARE registry, all patients under treatment with nusinersen who never had the ability to sit independently before start of treatment were identified for data analysis. Primary outcome of this analysis was the change in motor function evaluated with the CHOP INTEND score and motor milestones considering WHO criteria. Further, we evaluated data on the need for ventilator support and tube feeding, and mortality. In total, 143 patients with early-onset SMA were included in the data analysis with a follow-up period of up to 38 months. We observed major improvements in motor function evaluated with the CHOP INTEND score. Improvements were greater in children less than two years of age at start of treatment than in older children. 24.5% of children gained the ability to sit independently. Major improvements were observed during the first 14 months of treatment. The need for intermittent ventilator support and tube feeding increased despite treatment with nusinersen. Our findings confirm the increasing real-world evidence that treatment with nusinersen has a dramatic influence on disease progression and survival in patients with early-onset SMA. Major improvements in motor function are seen in children younger than two years at start of treatment. Bulbar and respiratory function needs to be closely monitored, as these functions do not improve equivalent to motor function.