Consistent Treatment Effect of Teriflunomide in Subgroups Based on Pre-Trial Therapy: Pooled Analyses of Temso and Tower

Background: Teriflunomide is a once-daily oral immunomodulator approved for the treatment of relapsing–remitting multiple sclerosis (RRMS). Phase 3 trials TEMSO (NCT00134563) and TOWER (NCT00751881) had similar designs and patient demographics allowing for pooling of data. In the pooled analyses, teriflunomide 14mg significantly reduced annualized relapse rate (ARR) and disability progression; teriflunomide 7mg significantly reduced ARR. Both doses had similar, manageable safety profiles. Pre-trial use of disease-modifying therapies (DMTs) or steroids (to treat attacks) and their subsequent discontinuation could imply more active or severe forms of MS; herein we present the pooled subgroup analysis from TEMSO-TOWER by pre-trial therapy.

Objectives: To assess the consistency of the teriflunomide effect on ARR and disability progression across subgroups based on pre-trial MS therapy.

Methods: TEMSO and TOWER enrolled patients with relapsing forms of MS, aged 18–55 years, with Expanded Disability Status Scale score ≤5.5, and ≥1 or ≥2 relapses in the 12 or 24 months before study entry, respectively. Patients were randomized 1:1:1 to once-daily teriflunomide 14mg (n=728) or 7mg (n=772), or placebo (n=751) for 108 weeks (TEMSO) or 48 weeks after last patient randomized (TOWER). Post-hoc analyses of ARR and 12-week confirmed disability progression were performed on pooled subgroups defined by pre-trial therapy: >1 prior DMT, 1 prior DMT, prior steroids only, and no prior MS treatment in the previous 2 years.

Results: Baseline disease characteristics were generally well balanced across subgroups, with differences reflecting varying stages of disease. Mean time since diagnosis of MS and most recent relapse varied (3.9 yrs [steroids only] to 7.3 yrs [>1 prior DMT]; 4.8 months [steroids only] to 6.4 months [>1 prior DMT], respectively). Efficacy of 14mg was consistent across the subgroups defined by pre-trial MS therapy for ARR and disability progression, with all estimates of treatment effect favoring teriflunomide vs placebo and no statistically significant (p>0.05) treatment-by-subgroup interaction. Similar results were observed for 7mg for ARR.

Conclusions: Pooled subgroup analyses show consistent treatment effect of teriflunomide across subgroups defined by pre-trial DMT or prior use of steroids, including efficacy in patients with more active or severe disease activity at baseline.