Nusinersen demonstrates effectiveness in treating spinal muscular atrophy: findings from a three-year nationwide study in Korea

Abstract

Introduction: Nusinersen is the first drug approved for spinal muscular atrophy (SMA) treatment. In this study, we aimed to evaluate the long-term safety and efficacy of nusinersen, assess the therapeutic effects based on the treatment initiation timing and baseline motor function, and explore the perception of functional improvement from either parents or patients, utilizing 3-year nationwide follow-up data in South Korea.

Methods: We enrolled patients with SMA who were treated with nusinersen under the National Health Insurance coverage, with complete motor score records available and a minimum treatment duration of 6 months. To evaluate the motor function of patients, the Hammersmith Infant Neurological Examination-2 (HINE-2) was used for type 1 and the Expanded Hammersmith Functional Motor Scale (HFMSE) was used for types 2 and 3 patients. A significant improvement was defined as a HINE-2 score gain ≥5 for patients with type 1 and an HFMSE score ≥ 3 for patients with types 2 and 3 SMA. Effects of treatment timing were assessed. Patients with type 2 were further categorized based on baseline motor scores for outcome analysis. We also analyzed a second dataset from five tertiary hospitals with the information on parents/patients-reported impressions of improvement.

Results: The study comprised 137 patients, with 21, 103, and 13 patients representing type 1, 2, and 3 SMA, respectively. At the 3-year follow-up, the analysis encompassed 7 patients with type 1, 12 patients with type 2, and none with type 3. Nearly half of all enrolled patients across SMA types (42.8, 59.2 and 46.2%, respectively) reached the 2-year follow-up for analysis. Patients with type 1 SMA exhibited gradual motor function improvement over 1-, 2-, and 3-year follow-ups (16, 9, and 7 patients, respectively). Patients with type 2 SMA demonstrated improvement over 1-, 2-, and 3-year follow-ups (96, 61 and 12 patients, respectively). Early treatment from symptom onset resulted in better outcomes for patients with type 1 and 2 SMA. In the second dataset, 90.7% of 108 patients reported subjective improvement at the 1-year follow-up.

Conclusion: Nusinersen treatment for types 1-3 SMA is safe and effective in long-term follow-up. Early treatment initiation was a significant factor affecting long-term motor outcome.

Keywords: Spinraza; early treatment; long-term effect; nusinersen; spinal muscular atrophy.

Figure 1

Overview of the study inclusion criteria.

Figure 2

Motor score changes in patients with type 1 SMA (HINE-2). (A) Changes in the HINE-2 motor score in all the patients with type 1 SMA. Color codes in the graph refer to individual patients enrolled in the study. (B) Changes in the HINE-2 motor score from baseline in patients treated with nusinersen within 18 months of symptom onset and in patients treated 18 months after symptom onset. The number of patients at each time points are shown in the table below the graph. (C) Motor score changes of patients with type 1 SMA based on the number of SMN2 copies. SMA, spinal muscular atrophy, HINE-2: Hammersmith Infant Neurological Exam Section 2.

Figure 3

Motor score changes in patients with type 2 SMA (HFMSE). (A) Mean HFMSE motor score changes from baseline in patients with type 2 SMA. Bar graphs indicate the number of patients at each time point. (B) HFMSE motor score changes in different patient groups based on the baseline HFMSE score. The number of patients at each time points are shown in the table below the graph. (C) HFMSE motor score changes from baseline in patients with type 2 SMA at 2 years according to the interval from symptom onset to nusinersen injection. Patients with a HFMSE score of 0 at baseline are marked in red, and the patients with HFMSE score greater than 0 are marked in black. SMA, spinal muscular atrophy, HFMSE: Hammersmith Functional Motor Scale Expanded.

Figure 4

Motor score changes in the 0% group in patients with type 2 SMA (HFMSE). (A) Mean HFMSE motor score changes from baseline in patients with type 2 SMA with a baseline HFMSE score of 0. The patients were grouped according to ≤3 HFMSE score and > 3 HFMSE score improvements at 1 year of follow-up. Error bars depict standard deviations, and the number of patients at each time point is shown in the table below the graph. (B) HFMSE motor score changes in all the patients with type 2 SMA with baseline HFMSE scores of 0. Color codes in the graph refer to individual patients enrolled in the study. SMA, spinal muscular atrophy, HFMSE: Hammersmith Functional Motor Scale Expanded.

Figure 5

Motor score changes in all patients with type 3 SMA (HFMSE). Color codes in the graph refer to individual patients enrolled in the study. HFMSE: Hammersmith Functional Motor Scale.