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J Neurol Neurosurg Psychiatry. 2020 Jan;91(1):58-66. doi: 10.1136/jnnp-2019-321124. Epub 2019 Aug 29.

Consistent control of disease activity with fingolimod versus IFN β-1a in paediatric-onset multiple sclerosis: further insights from PARADIGMS.

Author information

1
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.
2
Immunology of Viral Infections and Autoimmune Diseases, Universite Paris 11 Faculte de Medecine, Le Kremlin-Bicetre, France.
3
Department of Pediatrics and Adolescent Medicine, German Center for Multiple Sclerosis in Childhood and Adolescence, University Medical Center Göttingen, Gottingen, Germany.
4
Perelman School of Medicine, University of Pennsylvania, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
5
Partners Pediatric Multiple Sclerosis Center, Massachusetts General Hospital, Boston, Massachusetts, USA.
6
Pediatric MS Center, NYU Langone Health, New York City, New York, USA.
7
Department of Neurology, University of California San Francisco, San Francisco, California, USA.
8
Neuroscience Department, Novartis Pharmaceuticals Corp, East Hanover, New Jersey, USA.
9
Statistics Department, GCE Solutions, Bloomington, Illinois, USA.
10
Neuroscience Development Unit, Novartis Pharma AG, Basel, Switzerland.

Abstract

BACKGROUND:

In 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.

OBJECTIVES:

To investigate (1) differences between treatment groups across subpopulations (treatment-naïve, younger/prepubertal patients); (2) disability progression.

METHODS:

ARRs 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.

RESULTS:

In 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.

CONCLUSIONS:

Fingolimod 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 NUMBER:

NCT01892722.

KEYWORDS:

PARADIGMS ; disability progression; fingolimod; gilenya; paediatric multiple sclerosis

Conflict of interest statement

Competing interests: KD received personal compensation for speaker activities from Novartis. PH received compensation for serving on a scientific advisory board from Novartis, and for speaking from Bayer Health care. BB has served as a remunerated central MRI reviewer for the present trial (Novartis). EW volunteers on an advisory board for a Novartis trial. She is a site PI for clinical trials with Roche and Novartis. JG in the last 3 years has received honoraria for lectures and consultancy fees from Bayer, Teva and Novartis. LK has received personal compensation for activities as a speaker, consultant and/or participant on an advisory board from Biogen Idec, Novartis, Teva Neurosciences and Multicell. In addition, LK has received royalty or licence fees from ER Squibb & Sons, Avenir, Johnson & Johnson and Osmotica, and has received research support from Novartis, Biogen Idec, Celgene Corporation and Genentech. TC has received personal compensation for advisory boards/consulting for F. Hoffman-La Roche, Biogen and Novartis; TC has also received financial support for research activities from Biogen, Merck Serono, Verily and Novartis. TS, GLP and MM are employees of Novartis.

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