Consistent Efficacy of Teriflunomide in Prespecified Subgroup Analyses from a Phase 3 Trial (TOPIC) in Patients with Early Multiple Sclerosis

Background: Teriflunomide is a once-daily oral immunomodulator approved for the treatment of relapsing-remitting MS. The TOPIC study (NCT00622700) evaluated the efficacy and safety of teriflunomide in patients with a first clinical episode suggestive of MS. Teriflunomide 14 mg reduced the risk of relapse indicating clinically definite MS (CDMS) by 42.6% (P=0.0087) and the risk of relapse or occurrence of a new magnetic resonance imaging (MRI) lesion (whichever occurred first) by 34.9% (P=0.0003) compared with placebo. Teriflunomide 7 mg reduced the risk of relapse indicating CDMS by 37.2% (P=0.0271) and of relapse or MRI lesion by 31.4% (P=0.0020) compared with placebo.

Objectives: To report prespecified subgroup analyses of teriflunomide treatment effects in TOPIC.

Methods: Patients (n=614) were randomized (1:1:1) and treated with once-daily teriflunomide 14 mg, 7 mg, or placebo for ≤108 weeks. The effect of teriflunomide on time to relapse indicating conversion to CDMS (primary endpoint) and on time to relapse or occurrence of a new MRI lesion (key secondary endpoint) was analyzed in subgroups defined by gender, age (< or ≥31 years), geographical region (Eastern Europe, Western Europe, the Americas, and Australia), monofocal/multifocal status, and baseline number of gadolinium-enhancing lesions (0 or ≥1) and total lesion volume (< or ≥5 mL). Consistency of treatment effects across subgroups was assessed using a Cox regression model utilizing a treatment-by-subgroup interaction test for each factor separately. The model included treatment, baseline monofocal/multifocal status, region, subgroup, and treatment-by-subgroup interaction as covariates.

Results: Patient characteristics were well balanced across treatment groups. The benefits of treatment on time to relapse were consistent across all predefined subgroups whether stratified according to demographic features or baseline disease characteristics, except for Eastern Europe in the teriflunomide 7-mg group (P value for interaction=0.0047), in which very few relapses were reported overall. The treatment effect was also observed across all subgroups for time to relapse or occurrence of a new MRI lesion, with no significant treatment by subgroup interaction.

Conclusions: Both doses of teriflunomide had a consistently positive effect on time to first relapse and time to relapse or occurrence of a new MRI lesion across patient subgroups defined by gender, age, monofocal/multifocal status, and baseline MRI variables.