Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
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SHR Neuro Krebs Kardio Lipid Stoffw Microb
Weiss, C; Becker, LL; Friese, J; Blaschek, A; Hahn, A; Illsinger, S; Schwartz, O; Bernert, G; von der Hagen, M; Husain, RA; Goldhahn, K; Kirschner, J; Pechmann, A; Flotats-Bastardas, M; Schreiber, G; Schara, U; Plecko, B; Trollmann, R; Horber, V; Wilichowski, E; Baumann, M; Klein, A; Eisenkölbl, A; Köhler, C; Stettner, GM; Cirak, S; Hasselmann, O; Kaindl, AM; Garbade, SF; Johannsen, J; Ziegler, A.
Efficacy fi cacy and safety of gene therapy with onasemnogene abeparvovec in children with spinal muscular atrophy in the D-A-CH-region: a population-based observational study
LANCET REG HEALTH-EU. 2024; 47: 101092
Doi: 10.1016/j.lanepe.2024.101092
Web of Science
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- Co-Autor*innen der Med Uni Graz
- Plecko Barbara
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- Abstract:
- Background Real-world data on gene addition therapy (GAT) with onasemnogene abeparvovec (OA), including all age groups and with or without symptoms of the disease before treatment are needed to provide families with evidence- based advice and realistic therapeutic goals. Aim of this study is therefore a population-based analysis of all patients with SMA treated with OA across Germany, Austria and Switzerland (D-A-CH). Methods This observational study included individuals with Spinal Muscular Atrophy (SMA) treated with OA in 29 specialized neuromuscular centers in the D-A-CH-region. A standardized data set including WHO gross motor milestones, SMA validated motor assessments, need for nutritional and respiratory support, and adverse events was collected using the SMArtCARE registry and the Swiss-Reg-NMD. Outcome data were analyzed using a prespecified fi ed statistical analysis plan including potential predictors such as age at GAT, SMN2 copy number, past treatment, and symptom status. Findings 343 individuals with SMA (46% male, 54% female) with a mean age at OA of 14.0 months (range 0-90, - 90, IQR 20.0 months) were included in the analysis. 79 (23%) patients were clinically presymptomatic at the time of treatment. 172 (50%) patients received SMN2 splice-modifying drugs prior to GAT (risdiplam: n = 16, nusinersen: n = 154, both: n = 2). Functional motor improvement correlated with lower age at GAT, with the best motor outcome in those younger than 6 weeks, carrying 3 SMN2 copies, and being clinically presymptomatic at time of treatment. The likelihood of requiring ventilation or nutritional support showed a significantly fi cantly increase with older age at the time of GAT and remained stable thereafter. Pre-treatment had no effect on disease trajectories. Liver- related adverse events occurred significantly fi cantly less frequently up to 8 months of age. All other adverse events showed an even distribution across all age and weight groups. Interpretation Overall, motor, respiratory, and nutritional outcome were dependent on timing of GAT and initial symptom status. It was best in presymptomatic children treated within the fi rst six weeks of life, but functional motor scores also increased significantly fi cantly after treatment in all age groups up to 24 months. Additionally, OA was best tolerated when administered at a young age. Our study therefore highlights the need for SMA newborn screening and immediate treatment to achieve the best possible benefit fi t-risk ratio. Funding The SMArtCARE and Swiss-Reg-NMD registries are funded by different sources (see acknowledgements). Copyright (c) 2024 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
- Find related publications in this database (Keywords)
- Spinal muscular atrophy
- Gene addition therapy
- SMA
- Onasemnogene abeparvovec
- Gene therapy
- Zolgensma