Teriflunomide Reduces the Risk of Disease Activity for MS Patients
- Tue, 6/19/12 - 8:50am
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New Orleans—Teriflunomide—a novel, oral, once-daily disease-modifying therapy (DMT) currently in development for the treatment of relapsing forms of multiple sclerosis (MS)—significantly increased the proportion of patients free from disease activity compared with placebo, according to results from a post hoc analysis presented during a poster session at the AAN meeting. The poster was titled Teriflunomide Increases the Proportion of Patients Free from Disease Activity in the TEMSO Phase III Study.
Before discussing the effects of teriflunomide in reducing the risk of disease activity in patients with relapsing MS over a 2-year period, the authors provided background information on the TEMSO (Teriflunomide Multiple Sclerosis Oral) trial. TEMSO was a multinational, randomized, placebo-controlled, double-blind, parallel-group study, and the first pivotal phase 3 study to report findings.
The results showed that both 7-mg and 14-mg daily doses of teriflunomide significantly reduced annualized relapse rate by >30% (P<.001 vs placebo), with the risk of 12-week confirmed disability progression reduced by 30% in the 14-mg group (P=.03 vs placebo). Both doses were superior to placebo in a dose-dependent fashion on a range of magnetic resonance imaging (MRI) end points. Sustained disease-free activity (no clinical relapse, no sustained disability progression, and no MRI activity) is an important objective in the treatment of immune-related inflammatory diseases.
The post hoc analysis evaluated time to disease activity (a composite end point defined by confirmed clinical relapse, 12-week sustained disability progression, or new unique lesions [new T1 gadolinium-enhancing lesions or new/relapsed T2 lesions]). For the study, eligible patients were stratified according to baseline Kurtzke Expanded Disability Status Scale (EDSS) score (≤3.5 vs >3.5), and were randomized in a 1:1:1 ratio to receive once-daily teriflunomide 7 mg (n=366), teriflunomide 14 mg (n=359), or placebo (n=363), and treated for approximately 2 years.
Compared with study populations in recent large trials of investigational DMTs, patients in the TEMSO study had slightly higher levels of disease activity, as measured by number of relapses before study entry, baseline EDSS score, and MRI measures. The mean EDSS score was similar among all 3 treatment arms (2.67 for 14-mg teriflunomide and 2.68 for both 7-mg teriflunomide and placebo). Also similar was the mean number of relapses in the previous 2 years (2.2 for the 14-mg teriflunomide and placebo groups and 2.3 for the 7-mg teriflunomide group).
After 108 weeks of treatment, a greater number of patients receiving teriflunomide 7 mg and 14 mg compared with those receiving placebo remained disease-activity free (67 [18.4%], 82 [22.9%], and 52 [14.3%], respectively). Both teriflunomide doses increased the chances of being disease-activity free, compared with placebo (P=.0002 and P=.0293 for 14-mg and 7-mg teriflunomide, respectively). Hazard ratios were 0.726 (95% confidence interval [CI], 0.617-0.855) for 14-mg teriflunomide and 0.834 (95% CI, 0.711-0.978) for 7-mg teriflunomide versus placebo.
There was a dose-dependent effect of teriflunomide on the composite end point of disease activity (clinical relapse, disability progression, and new unique active lesions) in patients treated for 108 weeks. The 14-mg and 7-mg teriflunomide treatment arms had higher proportions of relapse-free patients, compared with placebo (60.6%, 57.8%, and 49.3%, respectively).—Eileen Koutnik-Fotopoulos
This study was supported by sanofi-aventis.