Nusinersen treatment in adult patients with spinal muscular atrophy: a safety analysis of laboratory parameters.
ASO
Coagulation
Kidney
Liver
Platelets
Side effects
Toxicity
Journal
Journal of neurology
ISSN: 1432-1459
Titre abrégé: J Neurol
Pays: Germany
ID NLM: 0423161
Informations de publication
Date de publication:
Dec 2021
Dec 2021
Historique:
received:
02
03
2021
accepted:
16
04
2021
revised:
15
04
2021
pubmed:
27
4
2021
medline:
5
11
2021
entrez:
26
4
2021
Statut:
ppublish
Résumé
Nusinersen is an intrathecally administered antisense oligonucleotide (ASO) that improves motor function in patients with spinal muscular atrophy (SMA). In addition to efficacy, the safety of a therapy is the decisive factor for the success of the treatment. For some ASOs, various organ toxicities have been described, such as thrombocytopenia, renal and liver impairment, or coagulation abnormalities. However, systematic data on laboratory parameters under treatment with nusinersen are mainly available from studies in infants and children. Therefore, our aim was to assess the safety of nusinersen therapy in adult SMA patients. Laboratory data from 404 nusinersen injections performed in 50 adult patients with SMA type 2 and type 3 were retrospectively analyzed. The total observation period was 76.9 patient-years, and patients received up to 12 injections. Our data provides no new safety concerns. In cerebrospinal fluid (CSF), the mean white blood cell count and lactate remained stable over time. Total CSF protein increased by 2.9 mg/dL. No change in mean platelet count was observed under therapy. Only one patient showed sporadic mild thrombocytopenia. Coagulation parameters and inflammatory markers were stable. The mean creatinine level decreased by 0.09 mg/dL. Analysis of mean liver enzyme levels revealed no relevant changes during treatment. Our data demonstrate a favorable safety profile of nusinersen therapy in adult SMA patients under longer-term "real-world" conditions. In particular, we found no evidence of clinically relevant platelet declines, coagulopathies, or renal or hepatic organ toxicities, which are common concerns with the use of ASOs.
Sections du résumé
BACKGROUND
BACKGROUND
Nusinersen is an intrathecally administered antisense oligonucleotide (ASO) that improves motor function in patients with spinal muscular atrophy (SMA). In addition to efficacy, the safety of a therapy is the decisive factor for the success of the treatment. For some ASOs, various organ toxicities have been described, such as thrombocytopenia, renal and liver impairment, or coagulation abnormalities. However, systematic data on laboratory parameters under treatment with nusinersen are mainly available from studies in infants and children. Therefore, our aim was to assess the safety of nusinersen therapy in adult SMA patients.
METHODS
METHODS
Laboratory data from 404 nusinersen injections performed in 50 adult patients with SMA type 2 and type 3 were retrospectively analyzed.
RESULTS
RESULTS
The total observation period was 76.9 patient-years, and patients received up to 12 injections. Our data provides no new safety concerns. In cerebrospinal fluid (CSF), the mean white blood cell count and lactate remained stable over time. Total CSF protein increased by 2.9 mg/dL. No change in mean platelet count was observed under therapy. Only one patient showed sporadic mild thrombocytopenia. Coagulation parameters and inflammatory markers were stable. The mean creatinine level decreased by 0.09 mg/dL. Analysis of mean liver enzyme levels revealed no relevant changes during treatment.
CONCLUSION
CONCLUSIONS
Our data demonstrate a favorable safety profile of nusinersen therapy in adult SMA patients under longer-term "real-world" conditions. In particular, we found no evidence of clinically relevant platelet declines, coagulopathies, or renal or hepatic organ toxicities, which are common concerns with the use of ASOs.
Identifiants
pubmed: 33899154
doi: 10.1007/s00415-021-10569-8
pii: 10.1007/s00415-021-10569-8
pmc: PMC8563549
doi:
Substances chimiques
Oligonucleotides
0
nusinersen
5Z9SP3X666
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
4667-4679Informations de copyright
© 2021. The Author(s).
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