A Phase II study of the safety and efficacy of teriflunomide in multiple sclerosis with relapses.

Abstract

BACKGROUND:

Teriflunomide, a dihydro-orotate dehydrogenase inhibitor, has immunomodulatory effects, including the ability to suppress experimental allergic encephalomyelitis. In this randomized, double-blind, placebo-controlled Phase II study, the authors examined the safety and efficacy of oral teriflunomide in multiple sclerosis (MS) with relapses.

METHODS:

Patients (n = 179) with relapsing-remitting MS (n = 157) or secondary progressive MS with relapses (n = 22) were randomized to receive placebo, teriflunomide 7 mg/day, or teriflunomide 14 mg/day for 36 weeks. MRI brain scans were performed every 6 weeks. The primary endpoint was the number of combined unique active lesions per MRI scan. Secondary endpoints included MRI-defined disease burden, relapse frequency, and disability increase.

RESULTS:

The median number of combined unique active lesions per scan was 0.5, 0.2, and 0.3 in the placebo, teriflunomide 7 mg/day (p < 0.03 vs placebo), and teriflunomide 14 mg/day (p < 0.01 vs placebo) groups during the 36-week double-blind treatment phase. Teriflunomide-treated patients also had significantly fewer T1 enhancing lesions per scan, new or enlarging T2 lesions per scan, and new T2 lesions. Patients receiving teriflunomide 14 mg/day had significantly reduced T2 disease burden. Teriflunomide treatment resulted in trends toward a lower annualized relapse rate and fewer relapsing patients (14 mg/day only) vs placebo. Significantly fewer patients receiving teriflunomide 14 mg/day vs placebo demonstrated disability increase. Treatment was well tolerated; numbers of adverse events and serious adverse events were similar in all treatment groups.

CONCLUSION:

Oral teriflunomide was effective in reducing MRI lesions and was well tolerated in patients with relapsing multiple sclerosis.

• Authors: P W O'Connor, D Li, M S Freedman, A Bar-Or, G P A Rice, C Confavreux, D W Paty, J A Stewart, R Scheyer, Teriflunomide Multiple Sclerosis Trial Group, University of British Columbia MS/MRI Research Group
• Journal: Neurology (Neurology) Vol. 66 Issue 6 Pg. 894-900 (Mar 28 2006) ISSN: 1526-632X [Electronic] United States
• PMID: 16567708 (Publication Type: Clinical Trial, Phase II, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Immunologic Factors
• Isoxazoles
• Leflunomide

Topics

• Adult
• Double-Blind Method
• Female
• Headache (chemically induced)
• Humans
• Immunologic Factors (adverse effects, metabolism, therapeutic use)
• Isoxazoles (adverse effects, metabolism, therapeutic use)
• Leflunomide
• Male
• Middle Aged
• Multiple Sclerosis, Relapsing-Remitting (drug therapy, physiopathology)
• Nausea (chemically induced)