Safety analysis of laboratory parameters in paediatric patients with spinal muscular atrophy treated with nusinersen

TL;DR

This study shows that nusinersen treatment for spinal muscular atrophy in children is generally safe with no major laboratory concerns.

Contribution

The study provides new safety data on nusinersen in pediatric SMA patients through retrospective laboratory analysis.

Findings

Nusinersen was administered 213 times without safety concerns in 46 pediatric patients.

CSF total protein increased by 24.038 mg/L per injection, suggesting a need for monitoring.

No significant changes were observed in liver enzymes, creatinine, or platelet count.

Abstract

Spinal muscular atrophy (SMA) is a progressive neurodegenerative disorder that can be treated with intrathecal nusinersen, an antisense oligonucleotide. In addition to efficacy, safety is a determining factor in the success of any therapy. Here, we aim to assess the safety of nusinersen therapy in paediatric patients with SMA.

Laboratory data of paediatric patients with SMA who received nusinersen between October 2019 and May 2022 were retrospectively analysed.

During the observation period, 46 infants and children aged 2.9 months to 13.6 years received a total of 213 nusinersen doses without safety concerns. Inflammatory markers were stable throughout the study. International normalized ratio was increased by 0.09 per injection. Urea levels were increased by 0.108 mmol/L, and cystatin C decreased by 0.029 mg/L per injection. There were no significant changes in platelet count, activated partial thrombin time, creatinine levels or liver enzyme levels during treatment. The cerebrospinal fluid (CSF) leukocyte count remained stable, and total protein increased by 24.038 mg/L per injection.

Our data showed that nusinersen therapy is generally safe in children with SMA. Laboratory monitoring did not identify any persistent or significantly abnormal findings. CSF protein should be monitored to gain more insights.

Figures