Magnetic resonance imaging outcomes from a phase III trial of teriflunomide

Abstract

Objective: The purpose of this study was to determine the effects of oral teriflunomide on multiple sclerosis (MS) pathology inferred by magnetic resonance imaging (MRI). Methods: Patients (n=1088) with relapsing MS were randomized to once-daily teriflunomide 7 mg or 14 mg, or placebo, for 108 weeks. MRI was recorded at baseline, 24, 48, 72 and 108 weeks. Annualized relapse rate and confirmed progression of disability (sustained ≥12 weeks) were the primary and key secondary outcomes. The principal MRI outcome was change in total lesion volume. Results: After 108 weeks, increase in total lesion volume was 67.4% (p=0.0003) and 39.4% (p=0.0317) lower in the 14 and 7 mg dose groups versus placebo. Other measures favoring teriflunomide were accumulated enhanced lesions, combined unique activity, T2-hyperintense and T1-hypointense component lesion volumes, white matter volume, and a composite MRI score; all were significant for teriflunomide 14 mg and most significant for 7 mg versus placebo. Conclusions: Teriflunomide provided benefits on brain MRI activity across multiple measures, with a dose effect evident on several markers. These effects were also consistent across selected subgroups of the study population. These findings complement clinical data showing significant teriflunomide-related reductions in relapse rate and disease progression, and demonstrate containment of MRI-defined disease progression.

Treating relapsing–remitting multiple sclerosis: therapy effects on brain atrophy

“…Regarding teriflunomide, BV measures were only reported for the phase III TEMSO clinical trial: both doses of teriflunomide (7 and 14 mg.) failed to demonstrate a reduction in BV loss as compared to placebo [33] (Tables 1b, 2). However, when analysing not only global BV loss, but also tissue-specific BV changes, a significant reduction of white matter (WM) loss for both doses of teriflunomide as compared to placebo was observed [34].…”

New and Evolving Treatment Goals in Multiple Sclerosis – the Role of Teriflunomide

“…Results showed 29.8% (p=0.028) and 31.5% (p=0.044) relative risk reductions for 14 mg teriflunomide versus placebo for confirmed disability progression in the TEMSO and TOWER studies, respectively (Figure 1). 20,21 In the TEMSO study, teriflunomide 14 mg treatment resulted in a 67.4% relative reduction in new T2 lesion volume (p<0.001) 20,24 and an 80.4% reduction in the number of gadolinium (Gd)-enhancing T1 lesions per scan at week 108. 24 Recently, long-term data from TEMSO has been released: no new or unexpected adverse events (AEs) occurred in patients receiving teriflunomide for up to 9 years.…”

“…20,21 In the TEMSO study, teriflunomide 14 mg treatment resulted in a 67.4% relative reduction in new T2 lesion volume (p<0.001) 20,24 and an 80.4% reduction in the number of gadolinium (Gd)-enhancing T1 lesions per scan at week 108. 24 Recently, long-term data from TEMSO has been released: no new or unexpected adverse events (AEs) occurred in patients receiving teriflunomide for up to 9 years. Disease activity decreased in patients switching from placebo and remained low in patients continuing on teriflunomide.…”

Optimizing therapy early in multiple sclerosis: An evidence-based view

“…Gd+ T1 and new or enlarging T2 lesions). 50,54 Neither T1 nor T2 lesions were reported in TOWER. 51 In TEMSO, teriflunomide was associated with a beneficial effect on WM loss, whereas global BVL was not significantly reduced.…”