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

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) beta-1a. Objectives To investigate (1) differences between treatment groups across subpopulations (treatment-naive, 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-naive subpopulation, fingolimod reduced ARR and n/neT2 lesions by 85.8% and 53.4%, respectively versus INF beta-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 beta-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 beta-1a (including treatment-naive and younger patients) and resulted in less disability progression for up to 2 years.