Novel MS Drug Reduces Relapse Risk in All Subgroups

Honolulu—The investigational drug teriflunomide demonstrated consistent reductions in rates of relapse and disease progression among patients with relapsing-remitting multiple sclerosis (MS), independent of patient demographics and disease characteristics, according to subgroup analyses from the phase 3 TEMSO (Teriflunomide Multiple Sclerosis Oral) trial. Investigators presented a poster relaying data from the preplanned subgroup analyses at the AAN meeting, which they said showed no interaction between any baseline patient or disease characteristic and the effectiveness of the novel disease-modifying therapy (DMT) in patients with MS. The poster was titled A Placebo-Controlled Phase 3 Trial (TEMSO) of Oral Teriflunomide in Multiple Sclerosis with Relapses: Subgroup Analyses. The pivotal, multicenter TEMSO trial (n=1088) was placebo-controlled, randomizing similar numbers of eligible MS patients aged 18 to 55 years to once-daily doses of teriflunomide 7 mg (n=365), teriflunomide 14 mg (n=358), or placebo (n=363) for 2 years. Two of the 1088 patients did not receive treatment. At randomization, all participants scored ≤5.5 on the Kurtzke Expanded Disability Status Scale (EDSS), which was used as the baseline measure for assessing disability progression; progression was defined as a ≥1.0-point increase in EDSS score (or ≥0.5 points for patients with an EDSS score of >5.5 points at baseline) sustained for ≥12 weeks. TEMSO investigators found that teriflunomide reduced the annualized relapse rate (ARR) by 31.5% compared with placebo (P<.001). In addition, patients in the 14-mg teriflunomide group had a 30% lower risk of confirmed 12-week disease progression (P=.03 vs placebo). Teriflunomide was reportedly well tolerated. In conducting the subanalyses, investigators looked at relapse rates and disability progression in each study arm according to sex, age (<38 or ≥38 years), geographic region (Eastern or Western Europe or Americas), baseline EDSS score (≤3.5 or >3.5), number of relapses in the past 2 years, MS subtype (secondary progressive/progressive relapsing or relapsing-remitting), magnetic resonance imaging (MRI) parameters (gadolinium-enhancing T1 lesions and burden of disease <13 or ≥13 mL), and prior DMT use. The researchers used a Poisson regression model to assess the relationship between each covariate and the ARR for relapse. A log-rank test was used to calculate the estimated risk of 12-week confirmed disability progression for each subgroup. Both teriflunomide doses produced similar improvements in ARR for each subgroup compared with placebo, but none of the covariates demonstrated significant interaction with either dose of teriflunomide. The authors did observe a trend toward interaction between baseline EDSS score and the 14-mg dose, however, with notably greater improvement in ARR observed for patients with a baseline EDSS score >3.5 taking teriflunomide 14 mg compared with placebo (relative risk reduction, 39.4% vs 8.6%, respectively). On the secondary end point of confirmed 12-week disability progression, no statistically significant interaction was observed between any covariate analyzed and either teriflunomide dose. Having an EDSS score >3.5 at baseline was associated with a markedly lower probability of disability progression when using teriflunomide 7 mg (hazard reduction, 12.2% vs 58.7%, respectively) and teriflunomide 14 mg (hazard reduction, 18.1% vs 64.9%, respectively) compared with placebo, but the differences were not significant. The authors concluded that “the beneficial effect of teriflunomide on relapse rate and disease progression was homogeneous across demographics [and] clinical or MRI disease characteristics of the prospective defined subgroups in the TEMSO study population.” This study was supported by sanofi-aventis; sanofi-aventis employees are included among the poster’s authors.