The primary aim was to review the clinical outcomes of patients with Spinal Muscular Atrophy (SMA) treated with nusinersen at the Children’s Hospital of Philadelphia (CHOP). Additionally, data was analyzed to see if age, type, or motor status at administration predicted motor outcomes.

SMA is an autosomal recessive disorder characterized by progressive motor, bulbar and respiratory weakness. Clinical trials of nusinersen were in a small subset of patients, but it received a broad approval in December 2016. Since approval, we have treated a more diverse population of patients, including those with disease milder and more severe than those in the clinical trials.

Data was collected from 61 patients followed at CHOP for over a year after initiating nusinersen treatment. Data included age, gender, and SMA type as well as motor outcomes, including the CHOP Infant Test of Neuromuscular Disorders (CHOP INTEND) and Hammersmith Functional Motor Scale-Expanded (HFMSE). Longitudinal trends were studied via Trellis graphs, stratified by baseline factors, followed by multivariate linear and tree-based models to assess the collective role of baseline factors on motor outcomes.

On average, HFMSE and INTEND increased by 4.76 and 8.48 points respectively in SMA patients treated with nusinersen. Age was a significant predictor, with over 3-fold improvement in HFMSE and INTEND in patients younger than 5.5 years and 2.3 years respectively. There was a -74% rank correlation between age and CHOP INTEND score in SMA1 patients. Rank correlation between age and HFMSE scores was 47% in SMA2 and - 0.4% in SMA3. 50/54 patients with follow-up scores showed motor improvement or stability.

The majority of SMA patients showed improvement or stability after nusinersen treatment. Age is an important factor in predicting motor outcomes in SMA, but less so in SMA3. Floor and ceiling effects of motor outcome measures might limit their utility in certain patients.