Teriflunomide added to interferon-β in relapsing multiple sclerosis: A randomized phase II trial

Objective: To evaluate teriflunomide as add-on therapy to ongoing stable-dosed interferon-β (IFNβ) in patients with relapsing forms of multiple sclerosis (RMS). Methods: A total of 118 patients with RMS were randomly assigned 1:1:1 to receive oral placebo or teriflunomide, 7 or 14 mg, once daily for 24 weeks; 86 patients entered the 24-week extension. The primary objective was to evaluate safety; secondary objectives were to evaluate the effects of treatment on disease activity assessed by MRI and relapse rate. Results: Teriflunomide was well tolerated with a low and similar incidence of treatment-emergent adverse events (TEAEs) across the 3 groups; TEAEs led to treatment discontinuation of 4.9%, 8.1%, and 7.9% of patients in the placebo, 7-mg, and 14-mg groups, respectively. The number of gadolinium-enhancing T1 (T1-Gd) lesions was reduced in both teriflunomide groups, with relative risk reductions (RRRs) of 84.6% ( p = 0.0005) and 82.8% ( p p = 0.1104) and 14-mg group (RRR 70.6%, p = 0.0154). A trend toward dose-dependent reduction in annualized relapse rate was also noted (RRRs 32.6% [ p = 0.4355] and 57.9% [ p = 0.1005] for 7 and 14 mg, respectively). Conclusion: Teriflunomide as add-on therapy to IFNβ had acceptable safety and tolerability and reduced MRI disease activity compared with IFNβ alone. Classification of evidence: This study provides Class II evidence that teriflunomide, 7 and 14 mg, added to IFNβ, is safe. The T1-Gd lesion burden was significantly reduced with both teriflunomide doses.