Efficacy and Safety of Teriflunomide in Patients Switching from Other Disease-Modifying Therapies

Background: Teriflunomide is a once-daily oral immunomodulator approved for relapsing-remitting MS. In TEMSO (NCT00134563) and TOWER (NCT00751881) phase 3 studies, teriflunomide 14 mg significantly reduced annualized relapse rate (ARR) and risk of disability progression vs placebo in patients with relapsing forms of MS (RMS). The TENERE (NCT00883337) phase 3 study showed comparable results on time to failure between teriflunomide and subcutaneous interferon beta-1a (IFNβ-1a) in patients with RMS. Safety and tolerability of teriflunomide were consistent across all studies.

Objectives: To assess consistency of treatment effects based on baseline disease-modifying therapy (DMT) history in TEMSO/TOWER, and in patients switching from IFNβ-1a to teriflunomide in TENERE open-label extension.

Methods: Post hoc analyses of ARR and 12‑week confirmed disability progression were performed in TEMSO/TOWER (n=2251) according to patient subgroups defined by DMT use in last 2 years (≥2 prior DMTs; 1 prior DMT; 0 prior DMT). ARR was evaluated in patients enrolled in TENERE extension (n=237), including patients switching from IFNβ-1a to teriflunomide 14 mg.

Results: Pooled analysis of TEMSO/TOWER data demonstrated efficacy for teriflunomide 14 mg vs placebo across prior treatment subgroups for ARR and disability progression, with no significant treatment-by-subgroup interactions. ARRs were 0.423, 0.464, and 0.303 for teriflunomide 14 mg, and 0.794, 0.641, and 0.472 for placebo for ≥2 prior DMTs, 1 prior DMT, and 0 prior DMT, respectively, representing relative risk reductions of 46.7%, 27.7%, and 35.9% for 14 mg vs placebo; corresponding hazard rate reductions for teriflunomide-treated patients for risk of disability progression were 78.6%, 46.6%, and 17.4%. In TENERE extension, median treatment duration ranged from 1003 to 1009 days; relapse rates were low in all groups: 0.239 (patients switching from IFNβ-1a); 0.181 (patients continuing teriflunomide 14 mg); and 0.223 (patients switching from teriflunomide 7 mg to 14 mg), and there were no significant differences between groups. Incidence of treatment-emergent adverse events was similar in all groups in TENERE extension.

Conclusions: Analyses of pooled TEMSO/TOWER studies and TENERE extension demonstrate consistent efficacy for teriflunomide 14 mg, regardless of pretrial therapy, with treatment-naïve patients showing slightly smaller relative reductions in disability progression, reflective of lower background disease progression.