Real-world data on the effect of long-term treatment with nusinersen over > 4 years in a cohort of Swiss patients with spinal muscular atrophy.

Tscherter and Steiner share first authorship (equal contribution).

Introduction
Current disease-modifying treatments for spinal muscular atrophy (SMA) have been shown to significantly improve the course of the disease, but data on long-term real-world outcomes remain scarce.Methods
This prospective multicentre, observational study investigated 28 patients treated with nusinersen for 4.1-6.2 years. Motor function was assessed with the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND), Hammersmith Functional Motor Scale (Expanded) (HFMS/E) and the Revised Upper Limb Module (RULM). Patient global impression of improvement scale, respiratory and nutritional support were assessed.Results
Eight patients were 0-2.5 years old at treatment start and median gain of motor scores was 31.5 points in the CHOP-INTEND and 10 points in the HFMS/E. Three patients started part-time non-invasive ventilation and/or nutritional support during observation period. Fourteen patients were 3.5-16 years old and showed a median gain of 1 point in the HFMS/E. Four patients required non-invasive ventilation and/or nutritional support at treatment start, and three started support during observation period. Six patients were aged 16-45 years old and showed a median gain of 3.5 points in the HFMS/E. None needed chronic respiratory or nutritional support. After one year, 84 %, and after 4 years of treatment, 54 % of patients felt their condition had improved in the last 6 months.Conclusion
Our data confirm sustained gains of motor function in early-treated patients and disease stabilisation in patients in the chronic phase under nusinersen treatment.