Effects of Fingolimod on Magnetic Resonance Imaging Outcomes in Patients with Pediatric-Onset Multiple Sclerosis: Results from the Phase 3 Paradigms Study

Friday, June 1, 2018: 3:08 PM
209 (Nashville Music City Center)
Douglas L Arnold, MD , Montreal Neurological Institute, McGill University, Montreal, QC, Canada
Brenda Banwell, MD , Children's Hospital of Philadelphia, Philadelphia, PA
Amit Bar-Or, MD , Neuroimmunology Unit, Montreal Neurological Institute and Hospital, Montreal, QC, Canada
Angelo Ghezzi, MD , Gallarate Hospital, Gallarate, Italy
Benjamin Greenberg, MD, MHS , Neurology & Neurotherapeutics - MS Clinic, UT Southwestern Medical Center, Dallas, TX
Emmanuelle Waubant, MD, PhD , UCSF Neurology, Weill Institute for Neurosciences, San Francisco, CA
Gavin Giovannoni, PhD , Queen Mary University of London, Blizard Institute, Barts and the London School of Medicine and Dentistry, London, UK, London, United Kingdom
Jerry S Wolinsky, MD , McGovern Medical School, UTHealth, Houston, TX
Jutta Gaertner, MD , Department of Paediatrics and Adolescent Medicine, German Centre for Multiple Sclerosis in Childhood and Adolescence University Medical Centre, Goettingen, Germany
Kevin Rostasy, MD , Division of Paediatric Neurology, Children's Hospital Datteln, University Witten/Herdecke, Datteln, Germany
Lauren Krupp, MD , Pediatric MS Center, NYU Langone Medical Center, New York, NY
Marc Tardieu, MD , Bicetre Hospital, Paris, France
Wolfgang Brueck, MD , Department of Neuropathology, University Medical Centre, Goettingen, Germany
Tracy Stites, PhD , Novartis Pharmaceuticals Corporation, East Hanover, NJ
Gregory L Pearce, PhD , Novartis Pharmaceuticals Corporation, East Hanover, NJ
Martin Merschhemke, MD, PhD , Novartis Pharma AG, Basel, Switzerland
Tanuja Chitnis, MD , Massachusetts General Hospital, Partners Pediatric MS Center, Boston, MA


About 3–5% of multiple sclerosis (MS) cases manifest in childhood and adolescence, characteristically with a highly active inflammatory disease course. Pediatric-onset MS (POMS) has an impact on brain integrity as a result of disruption of tissue microstructure, and may increase brain volume loss above age-expected rates.


To assess the effect of fingolimod up to 0.5 mg daily versus intramuscular interferon (IFN)β-1a 30 μg once weekly on predefined magnetic resonance imaging (MRI) outcomes in patients with POMS.


In this double-blind, double-dummy, active-controlled, parallel-group, multicenter study of up to 2 years, patients with POMS (aged 10–<18 years) were randomized to either oral fingolimod (dose adjusted for body weight; n=107) or IFNβ-1a (n=108). MRI was performed at baseline and then every 6 months until end of the study core phase and analyzed by a central reading center. Key MRI outcomes (number of patients included in each analysis, fingolimod/IFNβ-1a) were: number of new/newly enlarged T2 lesions (106/102 patients) and Gd-enhancing (Gd+) T1 lesions (106/101 patients), annual rate of brain volume change (96/89 patients), number of new T1 hypointense lesions (107/96 patients), change in total T2 hyperintense lesion volume (107/102 patients) and number of combined unique active (CUA) lesions (104/98 patients).


At the end of study (last MRI on study drug), compared with IFNβ-1a, fingolimod significantly reduced the annualized rate of new/newly enlarged T2 lesions by 52.6% (p<0.001) and the number of Gd+ T1 lesions per scan by 66.0% (p<0.001). Compared with IFNβ-1a, treatment with fingolimod up to 2 years significantly reduced the annualized rate of brain volume change (Least squares mean [95% CI]: −0.48 [–0.65,–0.30] vs −0.80 [–0.98,–0.61]; p=0.014), the annualized rate of new T1 hypointense lesions by 62.8% (p<0.001), T2 hyperintense lesion volume (percentage change from baseline: 18.4% vs 32.4%; p<0.001) and the number of CUA lesions per scan by 60.7% (p<0.001).


In patients with POMS, fingolimod significantly reduced MRI activity and slowed brain volume loss for up to 2 years compared with IFNβ-1a.