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Original research
Consistent control of disease activity with fingolimod versus IFN β-1a in paediatric-onset multiple sclerosis: further insights from PARADIGMS
  1. Kumaran Deiva1,2,
  2. Peter Huppke3,
  3. Brenda Banwell4,
  4. Tanuja Chitnis5,
  5. Jutta Gärtner3,
  6. Lauren Krupp6,
  7. Emmanuelle Waubant7,
  8. Tracy Stites8,
  9. Gregory Lewis Pearce9,
  10. Martin Merschhemke10
  1. 1 Department of Pediatric Neurology, National Referral Center for Rare Inflammatory Brain and Spinal Diseases, Hopitaux Universitaires Paris-Sud, Le Kremlin-Bicetre, France
  2. 2 Immunology of Viral Infections and Autoimmune Diseases, Universite Paris 11 Faculte de Medecine, Le Kremlin-Bicetre, France
  3. 3 Department of Pediatrics and Adolescent Medicine, German Center for Multiple Sclerosis in Childhood and Adolescence, University Medical Center Göttingen, Gottingen, Germany
  4. 4 Perelman School of Medicine, University of Pennsylvania, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
  5. 5 Partners Pediatric Multiple Sclerosis Center, Massachusetts General Hospital, Boston, Massachusetts, USA
  6. 6 Pediatric MS Center, NYU Langone Health, New York City, New York, USA
  7. 7 Department of Neurology, University of California San Francisco, San Francisco, California, USA
  8. 8 Neuroscience Department, Novartis Pharmaceuticals Corp, East Hanover, New Jersey, USA
  9. 9 Statistics Department, GCE Solutions, Bloomington, Illinois, USA
  10. 10 Neuroscience Development Unit, Novartis Pharma AG, Basel, Switzerland
  1. Correspondence to Dr Kumaran Deiva, Department of Pediatric Neurology, National Referral Center for Rare Inflammatory Brain and Spinal Diseases, Hopitaux Universitaires Paris-Sud, Le Kremlin-Bicetre 94276, France; kumaran.deiva{at}bct.aphp.fr

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.

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

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Footnotes

  • Contributors KD, PH, BB, TC, JG, LK and EW were principal investigators, involved in the design and/or ongoing conduct of the study, responsible for data collection and involved in the data analyses. TS, GLP and MM are Novartis associates and were involved in study design, study conduct and analyses. All authors contributed to writing and critical review at all stages of manuscript preparation and approved final content for publication.

  • Funding This work was supported by Novartis Pharma AG, Basel, Switzerland.

  • 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.

  • Patient consent for publication Not required.

  • Ethics approval The study protocol was approved by an institutional review board or ethics committee at each study site; the central institutional review board was Quorum Review IRB, Seattle, Washington, file number 28233/1.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Once the 5-year open-label extension has been completed, the reader will be able to request the raw data (anonymized) and related documents (e.g., protocol, reporting and analysis plan, clinical study report) that underlie the results reported in this article by connecting to https://www.clinicalstudydatarequest.com and signing a Data Sharing Agreement with Novartis. These will be made available to qualified external researchers, with requests reviewed and approved by an independent review panel on the basis of scientific merit.

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