Miller AE, O'Connor P, Wolinsky JS, Confavreux C, Kappos L, Olsson TP, Truffinet P, Wang L, D'Castro L, Comi G, Freedman MS; for the Teriflunomide Multiple Sclerosis Trial Group.Pre-specified subgroup analyses of a placebo-controlled phase III trial (TEMSO) of oral teriflunomide in relapsing multiple sclerosis. Mult Scler. 2012 Jun 21. [Epub ahead of print]
Background:The Teriflunomide Multiple Sclerosis Oral (TEMSO) trial, a randomized, double-blind, placebo-controlled phase III study, demonstrated that teriflunomide significantly reduced annualized relapse rate (ARR), disease progression and magnetic resonance imaging (MRI) activity, with a favorable safety profile in relapsing multiple sclerosis (RMS) patients.
Objective:The purpose of this study was to report the effects of teriflunomide on ARR and disability progression in pre-specified subgroups.
Methods:RMS patients (n=1088) were randomized to placebo or teriflunomide, 7 mg or 14 mg, once daily, for 108 weeks. Subgroup analyses were performed for ARR and disability progression by baseline demographics (gender, race, age), disease characteristics (Expanded Disability Status Scale (EDSS) strata, relapse history, multiple sclerosis (MS) subtype), MRI parameters (gadolinium-enhancing lesions, total lesion volume) and prior use of MS drugs. A generalized estimating equation method and Cox regression model were used to assess consistency of the treatment effect across subgroups, utilizing a treatment-by-subgroup interaction test for each factor separately.
Results:Reductions in ARR and disability progression were consistent across subgroups in favor of teriflunomide, with no treatment-by-subgroup interaction test reaching statistical significance.
Conclusion:The positive effects of teriflunomide were demonstrated consistently across subgroups in TEMSO.
The TEMSO study was reported as a news flash where it was claimed that teriflunomide was benefical in most MSers and the full trial has been published and showed that both 7 mg and 14 mg once-daily oral doses of teriflunomide significantly reduced the annualized relapse rate (ARR) (relative risk reductions: 31.2% (p=0.0002) and 31.5% (p=0.0005)) and 12-week confirmed disability progression (hazard ratio reductions: 23.7% (p=0.0835) and 29.8% (p=0.0279)) compared with placebo .
We have reported on the TOWER teriflunomide study and other studies involving teriflunomide. In TOWER, a double-blind, multi-center trial enrolled 1,169 MSers and compared once-daily treatment with either 7 mg (There was a 22% reduction in relapse) or 14 mg (there was about a 35% reduction in relapse) oral teriflunomide against placebo, with a modest reduction of relapses at the 14mg dose.
The objective of current report was to determine whether the effects of both doses of teriflunomide on ARR and disability progression were demonstrated consistently in a range of pre-specified patient subgroups from the TEMSO study related to demographic and disease characteristics at baseline.
Although there was no difference in relapse rate between placebo and secondary progressive MSers this would be expected as the number of relapses in SPMS is reduced. However there was some influence in the rate of progression in this group.
This study shows there is not one group of MSers (based on sex, age, EDSS status, Location, number of relapses etc.) who benefit over another group it works as well, or not, in all groups.
CoI: None. Prof G multiple