Teriflunomide Efficacy in Newly Diagnosed Patients with RMS Enrolled in the TEMSO and TOWER Studies: A Post Hoc Analysis

Background: Teriflunomide is a once-daily oral immunomodulator approved for the treatment of relapsing-remitting MS. In the placebo-controlled phase 3 studies in relapsing MS, TEMSO (NCT00134563) and TOWER (NCT00751881), teriflunomide significantly reduced annualized relapse rate (ARR). Teriflunomide 14 mg also significantly reduced unique active lesions per scan in TEMSO in which magnetic resonance imaging (MRI) was performed.

Objectives: To evaluate efficacy of teriflunomide in the newly diagnosed subgroup of patients from TEMSO and TOWER.

Methods: Newly diagnosed patients included in this post hoc analysis of the TEMSO and TOWER studies were defined as those diagnosed with relapsing forms of MS within 1 year of enrollment and naïve to disease-modifying therapies. Treatment efficacy was evaluated by ARR (pooled analysis) and unique active lesions per scan (TEMSO only). Both outcomes were assessed using a Poisson model, with treatment, baseline Expanded Disability Status Scale strata, region, and baseline value as covariates, and study as an additional covariate in the pooled analysis.

Results: In the pooled analysis, 587 newly diagnosed patients with relapsing MS were randomized to receive once-daily teriflunomide 14 mg (n=183), 7 mg (n=189), or placebo (n=215). Relative reductions in ARR in newly diagnosed patients treated with teriflunomide vs placebo were 37.8% (95% confidence interval [CI], 10.9 to 56.6; P=0.0096) and 24.3% (95% CI, -2.0 to 43.8; P=0.0677) in the 14 mg and 7 mg groups, respectively. The respective ARRs were 0.270, 0.328, and 0.433 in the 14 mg, 7 mg, and placebo groups. In TEMSO, relative reduction in number of unique active lesions per scan vs placebo group (n=99) was 64.6% (95% CI, 33.6 to 81.2; P=0.0012) in the 14 mg group (n=80) and 47.3% (95% CI, 22.2 to 64.3; P=0.0013) in the 7 mg group (n=88). MRI endpoints were not evaluated in TOWER.

Conclusions: Consistent with results from individual trials, pooled data from TEMSO and TOWER demonstrated significant reductions in ARR in newly diagnosed patients with MS treated with teriflunomide 14 mg. Additionally, significant reductions in the number of unique active lesions were observed in newly diagnosed patients in TEMSO. Together with the results of the TOPIC study (NCT00622700) in patients with a first clinical episode suggestive of MS, this post hoc analysis supports a consistent positive effect of teriflunomide on clinical and MRI measures early in the disease.