Long-term natural history in type II and III spinal muscular atrophy: a 4-year international study on the Hammersmith Functional Motor Scale Expanded.
Hammersmith Functional Motor Scale Expanded
long‐term results
motor function
spinal muscular atrophy
Journal
European journal of neurology
ISSN: 1468-1331
Titre abrégé: Eur J Neurol
Pays: England
ID NLM: 9506311
Informations de publication
Date de publication:
11 Oct 2024
11 Oct 2024
Historique:
revised:
23
09
2024
received:
17
07
2024
accepted:
24
09
2024
medline:
11
10
2024
pubmed:
11
10
2024
entrez:
11
10
2024
Statut:
aheadofprint
Résumé
Spinal muscular atrophy (SMA) is a genetic disorder caused by SMN1 gene mutations. Although studies on available disease-modifying treatments have reported their efficacy and safety, long-term natural history data are lacking for comparison. The aim of this prospective study was to report 4-year changes on the Hammersmith Functional Motor Scale Expanded (HFMSE) in type II and III SMA in relation to several variables such as age, functional status and SMN2 copy number. The study involves retrospective analysis of prospectively collected data from international datasets (Belgium, Italy, Spain, USA, UK). HFMSE longitudinal changes were analyzed using linear mixed effect models, examining annualized HFMSE change and its association with variables such as age at baseline, sex, motor function, SMN2 copy number. In SMA type II (n = 226), the 4-year mean change was -2.20 points. The largest mean changes were observed in sitters aged 5-14 years and the lowest in those who lost the ability to sit unsupported. In SMA type III (n = 162), the 4-year mean change was -2.75 points. The largest mean changes were in those aged 7-15 years, whilst the lowest were in those below 7 and in the SMA type IIIa subgroup over 15. Age and score at baseline were predictive of 4-year changes. Our findings provide natural history reference data for comparison with long-term follow-up of clinical trials or real-world data, highlighting the need to define patterns of changes in smaller SMA subgroups instead of reporting mean changes across an entire SMA cohort.
Sections du résumé
BACKGROUND AND PURPOSE
OBJECTIVE
Spinal muscular atrophy (SMA) is a genetic disorder caused by SMN1 gene mutations. Although studies on available disease-modifying treatments have reported their efficacy and safety, long-term natural history data are lacking for comparison. The aim of this prospective study was to report 4-year changes on the Hammersmith Functional Motor Scale Expanded (HFMSE) in type II and III SMA in relation to several variables such as age, functional status and SMN2 copy number.
METHODS
METHODS
The study involves retrospective analysis of prospectively collected data from international datasets (Belgium, Italy, Spain, USA, UK). HFMSE longitudinal changes were analyzed using linear mixed effect models, examining annualized HFMSE change and its association with variables such as age at baseline, sex, motor function, SMN2 copy number.
RESULTS
RESULTS
In SMA type II (n = 226), the 4-year mean change was -2.20 points. The largest mean changes were observed in sitters aged 5-14 years and the lowest in those who lost the ability to sit unsupported. In SMA type III (n = 162), the 4-year mean change was -2.75 points. The largest mean changes were in those aged 7-15 years, whilst the lowest were in those below 7 and in the SMA type IIIa subgroup over 15. Age and score at baseline were predictive of 4-year changes.
CONCLUSIONS
CONCLUSIONS
Our findings provide natural history reference data for comparison with long-term follow-up of clinical trials or real-world data, highlighting the need to define patterns of changes in smaller SMA subgroups instead of reporting mean changes across an entire SMA cohort.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e16517Subventions
Organisme : Biogen
Organisme : Novartis
Organisme : Roche Italia
Organisme : Ministero della Salute
ID : GR-2018-12365706
Organisme : Ministero della Salute
ID : GR-2021-12374579
Organisme : Ministero della Salute
ID : RF-2019-12370334
Investigateurs
Ilaria Cavallina
(I)
Enrica Rolle
(E)
Federica Ricci
(F)
Tiziana Mongini
(T)
Riccardo Masson
(R)
Riccardo Zanin
(R)
Maria Teresa Arnoldi
(MT)
Antonella Pini
(A)
Antonio Trabacca
(A)
Rafael S Rodriguez-Torres
(RS)
Nicola Forcina
(N)
Giulia Norcia
(G)
Giulia Stanca
(G)
Sara Carnicella
(S)
Lavinia Fanelli
(L)
Marion Main
(M)
Chiara Bravetti
(C)
Antonella Longo
(A)
Michela Nani
(M)
Laura Antonaci
(L)
Michela Catteruccia
(M)
Roberto Materia
(R)
Informations de copyright
© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.
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