Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jul;32(7):e70268.
doi: 10.1111/ene.70268.

Longitudinal Assessment of 4-Year HFMSE Changes in SMA II and III Patients Treated With Nusinersen

Giorgia Coratti  1   2 , Francesca Bovis  3 , Marika Pane  1   2 , Amy Pasternak  4 , Emilio Albamonte  5 , Irene Mizzoni  6 , Allan M Glanzman  7 , Simone Morando  8 , Jacqueline Montes  9 , Ilaria Cavallina  10 , Sally Dunaway Young  11 , Tina Duong  11 , Enrica Rolle  10 , Matthew Civitello  12 , Roberto De Sanctis  1   2 , Chiara Bravetti  2 , Federica Ricci  10 , Giulio Gadaleta  13 , Tiziana Mongini  13 , Maria Sframeli  14 , Maria Carmela Pera  1   2   15 , Sonia Messina  14 , Adele D'Amico  6 , Michela Catteruccia  6 , Noemi Brolatti  8 , Michio Hirano  9 , Zarazuela Zolkipli-Cunningham  16 , Basil T Darras  4 , Enrico Bertini  6 , Claudio Bruno  8 , John Day  11 , Valeria A Sansone  5 , Richard S Finkel  12 , Eugenio Mercuri  1   2 ; iSMAC/international SMA consortium
Collaborators, Affiliations

Longitudinal Assessment of 4-Year HFMSE Changes in SMA II and III Patients Treated With Nusinersen

Giorgia Coratti et al. Eur J Neurol. 2025 Jul.

Abstract

Background: The aim of this international retrospective study was to assess 4-year change using the Hammersmith Functional Motor Scale Expanded (HFMSE) in individuals with type II and III spinal muscular atrophy (SMA) treated with nusinersen and to establish predictors of HFMSE changes.

Methods: Individuals with type II or III SMA, and at least 4 years of nusinersen-only treatment were included. All were assessed using the HFMSE. Age at baseline, sex, motor function, SMN2 copy number, and age of onset were also retrospectively collected. Linear mixed effect models were used to calculate yearly changes and trajectory predictors.

Results: We included 73 individuals with SMA type II (mean age 8.58 years, SD 7.91, IQR 3.04-10.70) and 111 type III (mean age 7.91 years, SD 17.83, IQR 8.15-34.42). Over 4 years, mean changes were + 4.18 (95% CI: 2.85-5.50) for SMA II and + 1.08 (95% CI: 0.12-2.04) for SMA III. Age (SMA II: -0.34\[-0.51 to -0.17]; SMA III: -0.13\[-0.20 to -0.06], p < 0.001) and baseline HFMSE (SMA II: 1.02\[0.70-1.34]; SMA III: 0.79\[0.71-0.87], p < 0.001) were the strongest predictors of progression, with younger age and higher baseline scores associated with better outcomes. Functional status was only predictive for type III (6.96\[4.26-9.66]).

Conclusion: Our results confirm that, given a follow up of 4 years, there is a persistent impact of nusinersen on clinical progression that is better observed in younger patients with higher HFMSE scores at baseline, especially during the first 2 years of treatment.

Keywords: Hammersmith functional motor scale expanded; long term results; motor function; nusinersen; spinal muscular atrophy.

PubMed Disclaimer

Conflict of interest statement

Coratti G, Pane M, Pasternak A, Albamonte E, Pera MC, Glanzman A, Montes J, De Sanctis R, Duong T, Dunaway Young S, Civitello M, Sansone AV, D'Amico A, Bruno C, Messina S, Bertini E, Day J, Ricci F, Mongini T, Finkel R, and Mercuri E report personal fees for advisory boards, steering committees, speaker fees, or consultancies from BIOGEN S.R.L., ROCHE, AVEXIS and/or NOVARTIS outside the submitted work. Zolkipli‐Cunningham Z reports support from CURE SMA outside the submitted work. Bovis F, Rohwer A, Darras BT, Hirano M, Sframeli M, Catteruccia M, Mizzoni I, Rolle E, Bravetti C, Cavallina I, Morando S, Brolatti N, and Salmin F have nothing to disclose.

Figures

FIGURE 1
FIGURE 1
Four‐year progression in SMA Types II and III. (A) = SMA II; (B) = SMA IIIA; (C) = SMA IIIB. Left panels: Annual trajectories of HFMSE scores over 4 years, expressed as mean values with 95% confidence intervals. Middle panels: Distribution of changes in HFMSE scores from baseline to year 4. Each bar represents the proportion of patients who showed improvement or decline. The overlaid dashed line corresponds to the kernel density estimate of the distribution. Box‐and‐whisker plots indicate the median (central line), interquartile range (box), and values within 1.5 times the IQR (whiskers); individual outliers beyond this range are plotted as points. Mean values are marked with diamonds. Right panels: Individual patient‐level changes in HFMSE scores from baseline. Each bar corresponds to one patient.
FIGURE 2
FIGURE 2
Mean HFMSE scores with 95% CI at each time point in SMA II and SMA IIII subdivided by the included and excluded cohort. (A) = SMA II, (B) = SMA III. Blue solid line: Included patients, Red solid line: Excluded patients (red).
See this image and copyright information in PMC

References

    1. D'Amico A., Mercuri E., Tiziano F. D., and Bertini E., “Spinal Muscular Atrophy,” Orphanet Journal of Rare Diseases 6 (2011): 71. - PMC - PubMed
    1. Dubowitz V., “Chaos in Classification of the Spinal Muscular Atrophies of Childhood,” Neuromuscular Disorders 1 (1991): 77–80. - PubMed
    1. Audic F., Dubois S. M., Durigneux J., et al., “Effect of Nusinersen After 3 Years of Treatment in 57 Young Children With SMA in Terms of SMN2 Copy Number or Type,” Archives de Pédiatrie 31 (2024): 117–123. - PubMed
    1. Cho J., Lee J., Kim J., et al., “Nusinersen Demonstrates Effectiveness in Treating Spinal Muscular Atrophy: Findings From a Three‐Year Nationwide Study in Korea,” Frontiers in Neurology 14 (2023): 1294028. - PMC - PubMed
    1. Pane M., Coratti G., Pera M. C., et al., “Nusinersen Efficacy Data for 24‐Month in Type 2 and 3 Spinal Muscular Atrophy,” Annals of Clinical Translational Neurology 9 (2022): 404–409. - PMC - PubMed

LinkOut - more resources