Efficacy and Safety of Nusinersen Among Indian Children With Spinal Muscular Atrophy : A Prospective Cohort Study

Objectives:To study the efficacy and safety of Nusinersen among North Indian Children with SMA type2 and 3 compared with standard of care(SOC) over 12 months Methods:Prospective cohort study. Children with SMA 2/3 were screened. Motor assessments using Revised Hammersmith score(RHS), Revised upper limb module(RULM), WHO motor milestones were measured. Median and Ulnar nerve CMAPs and quality of life(QOL) were measured with ACEND at baseline and 12 months. Intra-thecal and treatment-emergent side effects of Nusinersen was noted. Outcome measures at 6 and 12 months were compared between the groups. Results:42 children with SMA, 16 in Nusinersen and 26 in SOC group were enrolled and followed for 12 months. Mean age at enrolment was 85±55 months; 26 (62%) were boys, 40% had SMA type2. Mean(SD) RHS score in the Nusinersen group increased from baseline 35±18.4 to 38.9±19.1 and 39.9±17.3 at 6 and12 months respectively, with mean gain of 4.9(SD) points over 12 months (p=0.001). RHS score in SOC increased from baseline of 28.8±15.7 to 29.6±16.6 and 29.9±17.2 at 6 and12 months respectively, with a mean gain of 1.1(SD) points over 12 months (p= 0.35). The mean gain in RHS score in Nusinersen group compared to the SOC group was significantly higher(p-value 0.02). Change in RULM, median and ulnar CMAPs, and QOL score within and across the groups was non-significant. Most adverse events were mild. Conclusion: Intra-thecal Nusinersen among children with late-onset SMA over 12-month duration was associated with significant improvement in RHS score compared to SOC. Nusinersen was safe and tolerated well.