Effect of fingolimod on MRI outcomes in patients with paediatric-onset multiple sclerosis: results from the phase 3 PARADIG MS study.

Objective: PARADIG MS demonstrated superior efficacy and comparable safety of fingolimod versus interferon β-1a (IFN β-1a) in paediatric-onset multiple sclerosis (PoMS). This study aimed to report all predefined MRI outcomes from this study.
Methods: Patients with multiple sclerosis (MS) (aged 10-<18 years) were randomised to once-daily oral fingolimod (n=107) or once-weekly intramuscular IFN β-1a (n=108) in this flexible duration study. MRI was performed at baseline and every 6 months for up to 2 years or end of the study (EOS) in case of early treatment discontinuation/completion. Key MRI endpoints included the annualised rate of formation of new/newly enlarging T2 lesions, gadolinium-enhancing (Gd+) T1 lesions, new T1 hypointense lesions and combined unique active (CUA) lesions (6 months onward), changes in T2 and Gd+ T1 lesion volumes and annualised rate of brain atrophy (ARBA).
Results: Of the randomised patients, 107 each were treated with fingolimod and IFN β-1a for up to 2 years. Fingolimod reduced the annualised rate of formation of new/newly enlarging T2 lesions (52.6%, p<0.001), number of Gd+ T1 lesions per scan (66.0%, p<0.001), annualised rate of new T1 hypointense lesions (62.8%, p<0.001) and CUA lesions per scan (60.7%, p<0.001) versus IFN β-1a at EOS. The percent increases from baseline in T2 (18.4% vs 32.4%, p<0.001) and Gd+ T1 (-72.3% vs 4.9%, p=0.001) lesion volumes and ARBA (-0.48% vs -0.80%, p=0.014) were lower with fingolimod versus IFN β-1a, the latter partially due to accelerated atrophy in the IFN β-1a group.
Conclusion: Fingolimod significantly reduced MRI activity and ARBA for up to 2 years versus IFN β-1a in PoMS.
Competing Interests: Competing interests: DLA receives grant support and consultant fees from Novartis, which manufactures the drug that is tested in this study. He also has an equity interest in NeuroRx Research, which performed the MRI analyses for the study. BB reports consultant fees and personal fees during the study conduct from Novartis, which manufactures the drug that is tested in this study. ABO reports personal fees from Novartis, which manufactures the drug that is tested in this study. AG reports personal fees during the study conduct from Novartis, which manufactures the drug that is tested in this study. BG reports personal fees from Novartis during the study conduct from Novartis, which manufactures the drug that is tested in this study. EW has nothing to disclose. GG reports consultant fees for steering committee and advisory board activities during the study conduct from Novartis, which manufactures the drug that is tested in this study. JW reports consultation fees for on a data monitoring committee (not this study) and during this study for steering committee participation from Novartis, which manufactures the drug that is tested in this study. JG reports consultant fees for research, lectures and advisory boards from Novartis, which manufactures the drug that is tested in this study. KR reports consultant fees for an advisory board from Novartis, which manufactures the drug that is tested in this study. LK reports personal fees personal fees during the study conduct from Novartis, which manufactures the drug that is tested in this study. MT reports personal fees for an advisory board during the study conduct from Novartis, which manufactures the drug that is tested in this study. WB reports grant support and personal fees during the study conduct from Novartis, which manufactures the drug that is tested in this study. TS is an employee of Novartis and holds some stocks and restricted stocks of the company. GLP has nothing to disclose. DAH is an employee of Novartis. MM is an employee of Novartis and holds some stocks and restricted stocks of the company. TC reports consultant fees for steering committee and advisory board activities during the study conduct from Novartis, which manufactures the drug that is tested in this study.
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