Spinal muscular atrophy type 3 and treatment adherence in a changing therapeutic landscape: a national-center experience.

Abstract

Aim: To report on treatment outcomes in adult patients with spinal muscular atrophy type 3 (SMA3) who had their nusinersen treatment initiated in adulthood.

Methods: The study enrolled 11 adults treated with nusinersen for SMA3 at the Croatian National Referral Centre for Neuromuscular Disorders from 2019 to 2022. We prospectively collected validated SMA outcome measures: Revised Hammersmith score (RHS), Revised Upper Limb Module, and 6-minute walk test (6MWT) as motor function outcomes and the Individualized Neuromuscular Quality of Life questionnaire. Baseline outcomes were compared with the outcomes after three years of treatment.

Results: All patients reported subjective improvement, and 9/11 reported an increased quality of life. Overall, 10/11 patients experienced clinically significant improvement in at least one measured outcome, while the remaining 1 patient reported the absence of disease progression. The mean increase in RHS was 2.7 points (P=0.062), and the mean increase in 6MWT was 39.7 m (P=0.239). Younger age and shorter disease duration correlated with better treatment outcomes (r=-0.543 and r=-0.666, respectively). After the approval of risdiplam in 2022, a third of patients chose to switch therapies despite observed subjective and objective positive nusinersen treatment effects.

Conclusion: Nusinersen had a positive treatment effect despite missed doses during the COVID-19 pandemic. Although the most significant improvements can be expected in patients treated the earliest, nusinersen treatment can be beneficial even in long-standing SMA.