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Abstract
Objective To evaluate the safety and clinical efficacy of nusinersen in patients older than 7 months with spinal muscular atrophy type 1 (SMA1).
Methods Patients with SMA1 were treated with nusinersen by intrathecal injections as a part of the Expanded Access Program (EAP; NCT02865109). We evaluated patients before treatment initiation (M0) and at 2 months (M2) and 6 months (M6) after treatment initiation. Survival, respiratory, and nutritional data were collected. Motor function was assessed with the modified Hammersmith Infant Neurologic Examination Part 2 (HINE-2) and physiotherapist scales adjusted to patient age (Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders and the Motor Function Measure 20 or 32).
Results We treated 33 children ranging in age from 8.3 to 113.1 months between December 2016 and May 2017. All patients were alive and were continuing treatment at M6. Median progress on the modified HINE-2 score was 1.5 points after 6 months of treatment (p < 0.001). The need for respiratory support significantly increased over time. There were no statistically significant differences between patients presenting with 2 and those presenting with 3 copies of the survival motor neuron 2 (SMN2) gene.
Conclusions Our results are in line with the phase 3 study for nusinersen in patients with SMA1 treated before 7 months of age and indicate that patients benefit from nusinersen even at a later stage of the disease.
ClinicalTrials.gov identifier: NCT02865109.
Classification of evidence This study provides Class IV evidence that for patients with SMA1 who are older than 7 months, nusinersen is beneficial.
GLOSSARY
- CHOP INTEND=
- Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders;
- EAP=
- Expanded Access Program;
- ENDEAR=
- A Study to Assess the Efficacy and Safety of Nusinersen (ISIS 396443) in Infants With Spinal Muscular Atrophy;
- HINE-2=
- Hammersmith Infant Neurologic Examination Part 2;
- MFM=
- Motor Function Measure;
- M0=
- before treatment;
- M2=
- 2 months of treatment;
- M6=
- 6 months of treatment;
- SMA=
- spinal muscular atrophy;
- SMN=
- survival motor neuron
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Class of Evidence: NPub.org/coe
Podcast: NPub.org/k8h4jv
CME Course: NPub.org/cmelist
- Received January 26, 2018.
- Accepted in final form June 29, 2018.
- © 2018 American Academy of Neurology
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