Teriflunomide Beneficial in Most Patients With Relapsing MS

Emma Hitt, PhD

July 05, 2011

July 5, 2011 (Lisbon, Portugal) — An analysis of magnetic resonance imaging (MRI) data from the TEMSO (Teriflunomide Multiple Sclerosis Oral) trial indicates that teriflunomide is effective in most multiple sclerosis (MS) patient subtypes.

"Teriflunomide has already shown to be superior to placebo across a wide range of MRI measures," said lead study author Flavia Nelson, MD, with the Department of Neurology at the University of Texas Health Sciences Center in Houston. "The post hoc subgroup analysis shows that these effects are homogeneous among the different subgroups divided by age, gender, disease severity, type of MS, and baseline MRI lesion burden among others," she told Medscape Medical News.

Dr. Nelson and colleagues presented the findings at the 21st Meeting of the European Neurological Society.

TEMSO is a randomized phase 3 trial comparing teriflunomide with placebo in 1088 patients with relapsing forms of MS. Patients received placebo or a 7-mg or 14-mg once daily dose of teriflunomide for 108 weeks.

Burden of disease as measured by MRI was the primary endpoint. Gadolinium (Gd)–enhancing T1 lesions and the number of unique active lesions were measured as secondary endpoints.

Overall, at week 108, teriflunomide significantly reduced brain MRI activity. Teriflunomide at a dose of 7 mg resulted in a 39.4% reduction in burden of disease compared with placebo (P = .03), whereas the 14-mg dose resulted in a 67.4% reduction at that time point (P < .001).

The number of Gd-enhancing T1 lesions and unique active lesions per scan were also reduced with both doses compared with placebo (P < .001 for all).

When MRI parameters were evaluated on the basis of patient baseline characteristics, effects were in favor of teriflunomide across all subgroups.

"There was a trend toward a dose effect, with greater improvements observed with the 14-mg dose," Dr. Nelson and colleagues note.

Teriflunomide is a metabolite of leflunomide. As an immunomodulatory drug, this agent inhibits pyrimidine de novo synthesis by blocking the enzyme dihydroorotate dehydrogenase, although its exact effect on MS lesions is unclear.

"Teriflunomide is a promising oral disease-modifying agent that could be used as a first-line agent," Dr. Nelson said. "The significance of an increase in white matter volume suggests a potential neuroprotective effect for this agent, and these findings need to be further explored," she added.

Independent commentator Stephen Krieger, MD, notes that this study provides confirmatory evidence of the efficacy of teriflunomide on standard MRI outcomes in MS. Dr. Krieger is an assistant professor of neurology at the Corinne Goldsmith Dickinson Center for MS at the Mount Sinai Medical Center in New York City.

"The data further support a dose-response curve to this agent at the doses studied, as was suggested by the disability data previously reported," he told Medscape Medical News.

"Although the exact relationship between MRI lesion burden and clinical outcomes varies between patients, teriflunomide has strongly positive data on these outcomes that lend support to its utility as a monotherapy disease-modifying agent in MS," Dr. Krieger added.

"In particular, the 80% reduction in gadolinium-enhancing lesions seen in the 14-mg group is roughly on par with our existing platform agents by this measure," he said. "Based on the clinical and MRI data to date, it remains to be seen if Sanofi-Aventis will seek regulatory approval for one or both doses of this agent," he added.

The study was supported by Sanofi-Aventis. Dr. Nelson reports that she has agreements or is a speaker for the National MS Society, Multiple Sclerosis Association of America, Bayer HealthCare, EMD Serono, Novartis, Sanofi-Aventis, Teva Neurosciences, Biogen Idec, and the University of Massachusetts Medical School. She received research or contractual support from the National Institutes of Health, Novartis, and Sanofi-Aventis. Dr. Krieger reports that he has worked in an educational and consultative capacity for the National MS Society, Bayer HealthCare, EMD Serono, Novartis, Teva Neuroscience, and Biogen Idec. He has received research support from the National MS Society and Bayer HealthCare.

21st Meeting of the European Neurological Society (ENS): Abstract O281. Presented May 30, 2011.

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