Effect of fingolimod on MRI outcomes in patients with paediatric-onset multiple sclerosis: Results from the phase 3 PARADIG MS study

Douglas L. Arnold, Brenda Banwell, Amit Bar-Or, Angelo Ghezzi, Benjamin M. Greenberg, Emmanuelle Waubant, Gavin Giovannoni, Jerry S. Wolinsky, Jutta Gärtner, Kevin Rostásy, Lauren Krupp, Marc Tardieu, Wolfgang Brück, Tracy E. Stites, Gregory L. Pearce, Dieter A. Häring, Martin Merschhemke, Tanuja Chitnis

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2 Scopus citations

Abstract

Objective PARADIGMS demonstrated superior efficacy and comparable safety of fingolimod versus interferon β-1a (IFN β-1a) in paediatric-onset multiple sclerosis (PoMS). This study aimed to report all predefined MRI outcomes from this study. Methods Patients with multiple sclerosis (MS) (aged 10-<18 years) were randomised to once-daily oral fingolimod (n=107) or once-weekly intramuscular IFN β-1a (n=108) in this flexible duration study. MRI was performed at baseline and every 6 months for up to 2 years or end of the study (EOS) in case of early treatment discontinuation/completion. Key MRI endpoints included the annualised rate of formation of new/newly enlarging T2 lesions, gadolinium-enhancing (Gd+) T1 lesions, new T1 hypointense lesions and combined unique active (CUA) lesions (6 months onward), changes in T2 and Gd+ T1 lesion volumes and annualised rate of brain atrophy (ARBA). Results Of the randomised patients, 107 each were treated with fingolimod and IFN β-1a for up to 2 years. Fingolimod reduced the annualised rate of formation of new/newly enlarging T2 lesions (52.6%, p<0.001), number of Gd+ T1 lesions per scan (66.0%, p<0.001), annualised rate of new T1 hypointense lesions (62.8%, p<0.001) and CUA lesions per scan (60.7%, p<0.001) versus IFN β-1a at EOS. The percent increases from baseline in T2 (18.4% vs 32.4%, p<0.001) and Gd+ T1 (-72.3% vs 4.9%, p=0.001) lesion volumes and ARBA (-0.48% vs-0.80%, p=0.014) were lower with fingolimod versus IFN β-1a, the latter partially due to accelerated atrophy in the IFN β-1a group. Conclusion Fingolimod significantly reduced MRI activity and ARBA for up to 2 years versus IFN β-1a in PoMS.

Original languageEnglish (US)
Pages (from-to)483-492
Number of pages10
JournalJournal of Neurology, Neurosurgery and psychiatry
Volume91
Issue number5
DOIs
StatePublished - May 1 2020

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology
  • Psychiatry and Mental health

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    Arnold, D. L., Banwell, B., Bar-Or, A., Ghezzi, A., Greenberg, B. M., Waubant, E., Giovannoni, G., Wolinsky, J. S., Gärtner, J., Rostásy, K., Krupp, L., Tardieu, M., Brück, W., Stites, T. E., Pearce, G. L., Häring, D. A., Merschhemke, M., & Chitnis, T. (2020). Effect of fingolimod on MRI outcomes in patients with paediatric-onset multiple sclerosis: Results from the phase 3 PARADIG MS study. Journal of Neurology, Neurosurgery and psychiatry, 91(5), 483-492. https://doi.org/10.1136/jnnp-2019-322138