Type I spinal muscular atrophy patients treated with nusinersen: 4-year follow-up of motor, respiratory and bulbar function.

BACKGROUND:We report the 4-year follow-up in type I patients treated with nusinersen and the changes in motor, respiratory and bulbar function in relation to subtype, age and SMN2 copy number. METHODS:The study included SMA 1 patients with at least one assessment after 12, 24 and 48 months from the first dose of nusinersen. The assessments used were Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) and the Hammersmith Infant Neurological Examination (HINE-II). RESULTS:Forty-eight patients, with ages ranging from 7 days to 12 years (mean 3.3 years, SD 3.6 years) were included in the study. The CHOP INTEND and HINE-II scores significantly increased between baseline and 48 months (p < 0.001). When age at starting treatment subgroups (<210 days, <2 years, 2-4 years, 5-11 years, ≥12 years) were considered, the CHOP INTEND increased significantly in patients younger than 4 years at treatment, while the HINE-2 increased significantly in patients younger than 2 years at treatment. In a mixed-model analysis, age, nutritional and respiratory status were predictive of changes on both scales while SMN2 copy number and decimal classification were not. CONCLUSIONS:Our results confirm the safety profile previously reported and support the durability of the efficacy of nusinersen at 4 years with an overall stability or mild improvement and no evidence of deterioration over a long period of time.