Continued benefit of nusinersen initiated in the presymptomatic stage of spinal muscular atrophy: 5-year update of the NURTURE study.
NURTURE
motor function
nusinersen
safety
spinal muscular atrophy
Journal
Muscle & nerve
ISSN: 1097-4598
Titre abrégé: Muscle Nerve
Pays: United States
ID NLM: 7803146
Informations de publication
Date de publication:
08 2023
08 2023
Historique:
revised:
10
05
2023
received:
09
08
2022
accepted:
14
05
2023
medline:
21
7
2023
pubmed:
6
7
2023
entrez:
6
7
2023
Statut:
ppublish
Résumé
NURTURE (NCT02386553) is an open-label study of nusinersen in children (two SMN2 copies, n = 15; three SMN2 copies, n = 10) who initiated treatment in the presymptomatic stage of spinal muscular atrophy (SMA). A prior analysis after ~3 y showed benefits on survival, respiratory outcomes, motor milestone achievement, and a favorable safety profile. An additional 2 y of follow-up (data cut: February 15, 2021) are reported. The primary endpoint is time to death or respiratory intervention (≥6 h/day continuously for ≥7 days or tracheostomy). Secondary outcomes include overall survival, motor function, and safety. Median age of children was 4.9 (3.8-5.5) y at last visit. No children have discontinued the study or treatment. All were alive. No additional children utilized respiratory intervention (defined per primary endpoint) since the prior data cut. Children with three SMN2 copies achieved all World Health Organization (WHO) motor milestones, with all but one milestone in one child within normal developmental timeframes. All 15 children with two SMN2 copies achieved sitting without support, 14/15 walking with assistance, and 13/15 walking alone. Mean Hammersmith Functional Motor Scale Expanded total scores showed continued improvement. Subgroups with two SMN2 copies, minimum baseline compound muscle action potential amplitude ≥2 mV, and no baseline areflexia had better motor and nonmotor outcomes versus all children with two SMN2 copies. These results demonstrate the value of early treatment, durability of treatment effect, and favorable safety profile after ~5 y of nusinersen treatment. Inclusion/exclusion criteria and baseline characteristics should be considered when interpreting presymptomatic SMA trial data.
Substances chimiques
nusinersen
5Z9SP3X666
Oligonucleotides
0
Banques de données
ClinicalTrials.gov
['NCT02386553']
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
157-170Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL069045
Pays : United States
Informations de copyright
© 2023 The Authors. Muscle & Nerve published by Wiley Periodicals LLC.
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