Effects of nusinersen after one year of treatment in 123 children with SMA type 1 or 2: a French real-life observational study.
MFM
Motor function measure
Nusinersen
Spinal muscular atrophy type I
Spinal muscular atrophy type II
Journal
Orphanet journal of rare diseases
ISSN: 1750-1172
Titre abrégé: Orphanet J Rare Dis
Pays: England
ID NLM: 101266602
Informations de publication
Date de publication:
12 06 2020
12 06 2020
Historique:
received:
04
10
2019
accepted:
18
05
2020
entrez:
14
6
2020
pubmed:
14
6
2020
medline:
22
6
2021
Statut:
epublish
Résumé
Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by degeneration of the anterior horn cells of the spinal cord. Nusinersen has been covered by public healthcare in France since May 2017. The aim of this article is to report results after 1 year of treatment with intrathecal nusinersen in children with SMA types 1 and 2 in France. Comparisons between treatment onset (T0) and after 1 year of treatment (Y1) were made in terms of motor function and need for nutritional and ventilatory support. Motor development milestone achievements were evaluated using the modified Hammersmith Infant Neurologic Examination-Part 2 (HINE-2) for patients under 2 years of age and Motor Function Measure (MFM) scores for patients over 2 years of age. Data on 204 SMA patients (type 1 or 2) were retrospectively collected from the 23 French centers for neuromuscular diseases. One hundred and twenty three patients had been treated for at least 1 year and were included, 34 of whom were classified as type 1 (10 as type 1a/b and 24 as type 1c) and 89 as type 2. Survival motor Neuron 2 (SMN2) copy numbers were available for all but 6 patients. Patients under 2 years of age (n = 30), had significantly higher HINE-2 scores at year 1 than at treatment onset but used more nutritional and ventilatory support. The 68 patients over 2 years of age evaluated with the Motor Function Measure test had significantly higher overall scores after 1 year, indicating that their motor function had improved. The scores were higher in the axial and proximal motor function (D2) and distal motor function (D3) parts of the MFM scale, but there was no significant difference for standing and transfer scores (D1). No child in either of the two groups achieved walking. Nusinersen offers life-changing benefits for children with SMA, particularly those with more severe forms of the disorder. Caregiver assessments are positive. Nevertheless, patients remain severely disabled and still require intensive support care. This new treatment raises new ethical challenges.
Sections du résumé
BACKGROUND
Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by degeneration of the anterior horn cells of the spinal cord. Nusinersen has been covered by public healthcare in France since May 2017. The aim of this article is to report results after 1 year of treatment with intrathecal nusinersen in children with SMA types 1 and 2 in France. Comparisons between treatment onset (T0) and after 1 year of treatment (Y1) were made in terms of motor function and need for nutritional and ventilatory support. Motor development milestone achievements were evaluated using the modified Hammersmith Infant Neurologic Examination-Part 2 (HINE-2) for patients under 2 years of age and Motor Function Measure (MFM) scores for patients over 2 years of age.
RESULTS
Data on 204 SMA patients (type 1 or 2) were retrospectively collected from the 23 French centers for neuromuscular diseases. One hundred and twenty three patients had been treated for at least 1 year and were included, 34 of whom were classified as type 1 (10 as type 1a/b and 24 as type 1c) and 89 as type 2. Survival motor Neuron 2 (SMN2) copy numbers were available for all but 6 patients. Patients under 2 years of age (n = 30), had significantly higher HINE-2 scores at year 1 than at treatment onset but used more nutritional and ventilatory support. The 68 patients over 2 years of age evaluated with the Motor Function Measure test had significantly higher overall scores after 1 year, indicating that their motor function had improved. The scores were higher in the axial and proximal motor function (D2) and distal motor function (D3) parts of the MFM scale, but there was no significant difference for standing and transfer scores (D1). No child in either of the two groups achieved walking.
CONCLUSION
Nusinersen offers life-changing benefits for children with SMA, particularly those with more severe forms of the disorder. Caregiver assessments are positive. Nevertheless, patients remain severely disabled and still require intensive support care. This new treatment raises new ethical challenges.
Identifiants
pubmed: 32532349
doi: 10.1186/s13023-020-01414-8
pii: 10.1186/s13023-020-01414-8
pmc: PMC7291731
doi:
Substances chimiques
Oligonucleotides
0
nusinersen
5Z9SP3X666
Types de publication
Journal Article
Observational Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
148Références
Arch Phys Med Rehabil. 2014 Nov;95(11):2064-2070.e1
pubmed: 24862765
N Engl J Med. 2018 Feb 15;378(7):625-635
pubmed: 29443664
Pediatr Phys Ther. 2011 Winter;23(4):322-6
pubmed: 22090068
N Engl J Med. 2017 Nov 2;377(18):1723-1732
pubmed: 29091570
Gene Ther. 2017 Sep;24(9):534-538
pubmed: 28467402
Neurology. 2019 May 21;92(21):e2492-e2506
pubmed: 31019106
Neurology. 2018 Oct 2;91(14):e1312-e1318
pubmed: 30158155
Lancet Neurol. 2012 May;11(5):443-52
pubmed: 22516079
Neuromuscul Disord. 2018 Mar;28(3):208-215
pubmed: 29433793
Neuromuscul Disord. 2018 Feb;28(2):103-115
pubmed: 29290580
Nat Genet. 1997 Jul;16(3):265-9
pubmed: 9207792
Arch Phys Med Rehabil. 2013 Nov;94(11):2218-26
pubmed: 23602884
Eur J Paediatr Neurol. 2018 Jan;22(1):122-127
pubmed: 29208343
Neurology. 2019 Aug 6;93(6):267-269
pubmed: 31235659
Muscle Nerve. 2018 Jan;57(1):142-146
pubmed: 28556387
Hum Genet. 2006 May;119(4):422-8
pubmed: 16508748
Neuromuscul Disord. 2015 Jul;25(7):593-602
pubmed: 26045156
Arch Pediatr. 2014 Apr;21(4):347-54
pubmed: 24630620
Lancet. 2017 Dec 17;388(10063):3017-3026
pubmed: 27939059
Ann Neurol. 2017 Dec;82(6):883-891
pubmed: 29149772
Neurology. 2016 Mar 8;86(10):890-7
pubmed: 26865511
Neuromuscul Disord. 2016 Nov;26(11):754-759
pubmed: 27769560
Ann Neurol. 2019 Sep;86(3):443-451
pubmed: 31228281