Nusinersen treatment in adults with severe spinal muscular atrophy: A real-life retrospective observational cohort study.
Journal
Revue neurologique
ISSN: 0035-3787
Titre abrégé: Rev Neurol (Paris)
Pays: France
ID NLM: 2984779R
Informations de publication
Date de publication:
Mar 2022
Mar 2022
Historique:
received:
03
09
2021
revised:
27
10
2021
accepted:
29
10
2021
pubmed:
11
1
2022
medline:
7
4
2022
entrez:
10
1
2022
Statut:
ppublish
Résumé
Spinal muscular atrophy (SMA) is a progressive neurodegenerative disease due to homozygous loss-of-function of the survival motor neuron gene SMN1 with absence of the functional SMN protein. Nusinersen, a costly intrathecally administered drug approved in 2017 in Europe, induces alternative splicing of the SMN2 gene, which then produces functional SMN protein, whose amount generally increases with the number of SMN2 gene copies. We retrospectively collected data from consecutive wheelchair-bound adults with SMA managed at a single center in 2018-2020. The following were collected at each injection, on days 1, 14, 28, 63, 183, and 303: 32-item Motor Function Measurement (MFM) total score and D2 and D3 subscores; the Canadian Occupational Performance Measure (COPM) performance and satisfaction scores; and lung function tests. The patients were divided into two groups based on whether their MFM total score was<or≥the mean (15.6%). Adverse events were recorded. We identified 18 patients who received 4 to 8 Nusinersen injections. No significant improvements occurred over time in any of the MFM scores or lung function test results, which did not differ between groups. The COPM performance score improved significantly from day 0 to day 303 in the high-MFM group and the COPM satisfaction score in the overall population from D0 to D183. Half the patients achieved the minimal clinically important difference for both COPM scores. The overall stability of conventional motor assessment in this population with advanced disabilities is encouraging to use more sensitive tools based on self-perception and autonomy in daily life activities, such as COPM. Our finding of a significant COPM performance score improvement from days 0 to 303 only in the patients with initial MFM-32 scores above the mean in the population suggests that the severity of the baseline disabilities may affect treatment efficacy. IV, retrospective observational cohort study.
Sections du résumé
BACKGROUND AND OBJECTIVES
OBJECTIVE
Spinal muscular atrophy (SMA) is a progressive neurodegenerative disease due to homozygous loss-of-function of the survival motor neuron gene SMN1 with absence of the functional SMN protein. Nusinersen, a costly intrathecally administered drug approved in 2017 in Europe, induces alternative splicing of the SMN2 gene, which then produces functional SMN protein, whose amount generally increases with the number of SMN2 gene copies.
METHODS
METHODS
We retrospectively collected data from consecutive wheelchair-bound adults with SMA managed at a single center in 2018-2020. The following were collected at each injection, on days 1, 14, 28, 63, 183, and 303: 32-item Motor Function Measurement (MFM) total score and D2 and D3 subscores; the Canadian Occupational Performance Measure (COPM) performance and satisfaction scores; and lung function tests. The patients were divided into two groups based on whether their MFM total score was<or≥the mean (15.6%). Adverse events were recorded.
RESULTS
RESULTS
We identified 18 patients who received 4 to 8 Nusinersen injections. No significant improvements occurred over time in any of the MFM scores or lung function test results, which did not differ between groups. The COPM performance score improved significantly from day 0 to day 303 in the high-MFM group and the COPM satisfaction score in the overall population from D0 to D183. Half the patients achieved the minimal clinically important difference for both COPM scores.
DISCUSSION
CONCLUSIONS
The overall stability of conventional motor assessment in this population with advanced disabilities is encouraging to use more sensitive tools based on self-perception and autonomy in daily life activities, such as COPM. Our finding of a significant COPM performance score improvement from days 0 to 303 only in the patients with initial MFM-32 scores above the mean in the population suggests that the severity of the baseline disabilities may affect treatment efficacy.
CLASSIFICATION OF EVIDENCE LEVEL
UNASSIGNED
IV, retrospective observational cohort study.
Identifiants
pubmed: 35000792
pii: S0035-3787(21)00789-X
doi: 10.1016/j.neurol.2021.10.010
pii:
doi:
Substances chimiques
Oligonucleotides
0
nusinersen
5Z9SP3X666
Types de publication
Journal Article
Observational Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
234-240Informations de copyright
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