Objective: The purpose of this study was to determine the effects of oral teriflunomide on multiple sclerosis (MS) pathology inferred by magnetic resonance imaging (MRI).
Methods: Patients (n=1088) with relapsing MS were randomized to once-daily teriflunomide 7 mg or 14 mg, or placebo, for 108 weeks. MRI was recorded at baseline, 24, 48, 72 and 108 weeks. Annualized relapse rate and confirmed progression of disability (sustained ≥12 weeks) were the primary and key secondary outcomes. The principal MRI outcome was change in total lesion volume.
Results: After 108 weeks, increase in total lesion volume was 67.4% (p=0.0003) and 39.4% (p=0.0317) lower in the 14 and 7 mg dose groups versus placebo. Other measures favoring teriflunomide were accumulated enhanced lesions, combined unique activity, T2-hyperintense and T1-hypointense component lesion volumes, white matter volume, and a composite MRI score; all were significant for teriflunomide 14 mg and most significant for 7 mg versus placebo.
Conclusions: Teriflunomide provided benefits on brain MRI activity across multiple measures, with a dose effect evident on several markers. These effects were also consistent across selected subgroups of the study population. These findings complement clinical data showing significant teriflunomide-related reductions in relapse rate and disease progression, and demonstrate containment of MRI-defined disease progression.
Keywords: Teriflunomide; clinical trial; disease-modifying therapy; magnetic resonance imaging; multiple sclerosis; phase III.