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J. Neurol. Neurosurg. Psychiatr. · Jan 2020
Randomized Controlled Trial Multicenter StudyConsistent control of disease activity with fingolimod versus IFN β-1a in paediatric-onset multiple sclerosis: further insights from PARADIGMS.
- Kumaran Deiva, Peter Huppke, Brenda Banwell, Tanuja Chitnis, Jutta Gärtner, Lauren Krupp, Emmanuelle Waubant, Tracy Stites, Gregory Lewis Pearce, and Martin Merschhemke.
- Department of Pediatric Neurology, National Referral Center for Rare Inflammatory Brain and Spinal Diseases, Hopitaux Universitaires Paris-Sud, Le Kremlin-Bicetre, France kumaran.deiva@bct.aphp.fr.
- J. Neurol. Neurosurg. Psychiatr. 2020 Jan 1; 91 (1): 58-66.
BackgroundIn PARADIGMS, a double-blind phase III trial in 215 paediatric patients with multiple sclerosis (MS) (10 to <18 years), fingolimod administered for up to 2 years significantly reduced the annualised relapse rate (ARR) and rate of new/newly enlarged T2 (n/neT2) lesions compared with interferon (IFN) β-1a.ObjectivesTo investigate (1) differences between treatment groups across subpopulations (treatment-naïve, younger/prepubertal patients); (2) disability progression.MethodsARRs at 10, 11 and 12 years were estimated based on predefined modelling extrapolations. Changes in Expanded Disability Status Scale (EDSS), and in 3 month (3M) and 6 month (6M) confirmed disability progression (CDP) were evaluated post hoc.ResultsIn the treatment-naïve subpopulation, fingolimod reduced ARR and n/neT2 lesions by 85.8% and 53.4%, respectively versus INF β-1a (both p<0.001), compared with 81.9% and 52.6% in the overall population. Model-based ARR reductions in younger patients (≤12 years) were 91.9%-94.6%. Twice as many IFN β-1a-treated than fingolimod-treated patients had worse EDSS scores at study end (20.6% vs 10.5%, p=0.043). Risk reductions in 3M-CDP and 6M-CDP were 77.2% (p=0.007) and 80.2% (p=0.040), respectively.ConclusionsFingolimod in paediatric MS was associated with consistent control of disease activity versus IFN β-1a (including treatment-naïve and younger patients) and resulted in less disability progression for up to 2 years.Trial Registration NumberNCT01892722.© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
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