The Paradigms Study: A Randomized Double-Blind Trial of Fingolimod Versus Interferon β-1a in Patients with Multiple Sclerosis Aged 10 to < 18 Years

BACKGROUND: Multiple sclerosis (MS) symptoms typically manifest in adulthood. In approximately 3–5% of cases, onset occurs before 18 years of age. Younger patients invariably have a relapsing–remitting form of MS (RRMS), with a 2–3-fold higher relapse rate than patients with adult-onset MS. The PARADIGMS trial is the first international controlled study to examine the efficacy and safety of fingolimod (FTY) in pediatric/adolescent patients. OBJECTIVES: To investigate the efficacy and safety of FTY up to 0.5 mg/day versus interferon β-1a (IFN β-1a) 30 μg intramuscularly (IM) in pediatric/adolescent patients with RRMS. METHODS: PARADIGMS was a randomized, double-blind, active-controlled, parallel-group trial of up to 2-year duration, followed by a 5-year open-label extension period in patients with MS aged 10 to < 18 years at randomization. Eligible patients must have had an Expanded Disability Status Scale (EDSS) score of 0 to 5.5, inclusive and ≥ 1 relapse in the past year, or 2 relapses in the previous 2 years, or have evidence of ≥ 1 gadolinium-enhancing (Gd+) lesion on magnetic resonance imaging (MRI) in the 6 months preceding randomization. Patients were randomized (1:1) to receive oral FTY up to a dose of 0.5 mg/day (dose adjusted for body weight) or IFN-β1a 30 μg IM once a week. The primary endpoint was annualized relapse rate. Key secondary endpoints included MRI- and relapse-related outcomes. Safety and tolerability were also assessed. RESULTS: In total, 215 patients were randomized. Most patients were female (62%, n = 134) and Caucasian (92%, n = 197). Mean age at randomization for the FTY and IFN-β1a groups was 15.2 and 15.4 years, respectively (median, 16.0; range, 10–17 and median, 16.0, range 11–18*, respectively). Mean disease duration since first symptom was 1.9 years for the FTY group and 2.4 years for the IFN-β1a group. The mean number of relapses in the past year was 1.5 for both groups and the median EDSS score was 1.5 for both groups. Primary efficacy results, MRI outcomes and safety and tolerability data will be presented at the meeting. CONCLUSION: PARADIGMS is the first randomized clinical trial in pediatric/adolescent patients with MS. Results will determine whether FTY is beneficial in this young patient population that has active disease, typically of a shorter clinical duration than patients with adult-onset MS.