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Teriflunomide Slows Brain Atrophy In Patients At Risk for MS Conversion

Results suggested that for every 1% of brain volume lost, a 51.7% increase in risk of clinically definite MS conversion was observed.

Robert Zivadinov, MD, PhD

A post hoc analysis has shown that teriflunomide (Aubagio, Sanofi) significantly slowed the rate of whole brain atrophy compared to placebo in patients with a first clinical episode suggestive of multiple sclerosis (MS), known as clinically isolated syndrome (CIS).

This brain volume loss reduction was additionally associated with a delay in the progression to clinically definite MS. Ultimately, at the final evaluation at 2 years, teriflunomide showed a 43% reduction in annual whole brain volume loss relative to placebo (P <.0001).

The data from the phase III TOPIC study were presented at the 34th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in Berlin, Germany.

“It is known that Aubagio can slow down the rate of brain atrophy in relapsing-remitting MS patients, but this is the first study to show that Aubagio can slow down brain volume loss from the earliest phases of the disease in patients with CIS,” Robert Zivadinov, MD, PhD, the director of the Translational Imaging Center at the Clinical Translational Research Center, and the director of the Buffalo Neuroimaging Analysis Center, told NeurologyLive. “Therefore, this is the first study to show that Aubagio reduces whole brain volume loss from disease onset.”

The TOPIC intent-to-treat (ITT) population of the post hoc analysis included patients receiving placebo (n = 197), teriflunomide 14 mg (n = 214), or teriflunomide 7 mg (n = 203) for ≤108 weeks. Post hoc, the blinded analysis of changes in whole brain volume was evaluated using longitudinal Structural Image Evaluation using Normalization of Atrophy (SIENA) analysis. Evaluations took place at months 6, 12, 18, and 24.

At month 6, the teriflunomide arm (n = 165) correlated with an 87.4% mean reduction in whole brain atrophy compared to placebo (n = 154; P = .02). Likewise, at month 12, use of the therapy (n = 135) had shown a correlated reduction of 28.6% in whole brain volume relative to placebo (n = 122; P =.03). At month 18, the reduction in brain atrophy was 36.1% relative to placebo (P = .0003).

“What was unexpected to observe in this study is the strength of the effect,” Zivadinov said. “A reduction of 42% of brain atrophy development with Aubagio compared to placebo over 2 years suggests that when Aubagio is given the at earliest possible time, its benefit is more pronounced.”

All told, the annual brain volume loss observed in patients treated with teriflunomide was, as Zivadinov stated, more prominent with earlier treatment. Study data showed that a 51.7% increase in risk of clinically definite MS conversion was seen for every 1% loss of brain volume (P <.0001).

“It is well known that patients who develop less brain atrophy have much higher likelihood to not progress in their cognitive and motor disability, which was confirmed also in the during extension of the TOPIC study,” Zivadinov said. “The effect was significant throughout the 24 months, became significant as early as 6 months from baseline, and was significant at every time point.”


1. Sanofi presents new data on Aubagio® (teriflunomide) [press release]. Cambridge, MA: Sanofi; Published October 10, 2018. https://bit.ly/2yQDIrM. Accessed October 16, 2018.

2. Zivadinov R, Dwyer MG, Carl E, Thangavelu K, Cavalier S, Bergsland N. Evaluating the effect of teriflunomide on whole brain atrophy in the phase 3 TOPIC study. Presented at: 34th ECTRIMS; October 11, 2018; Berlin, Germany. https://bit.ly/2NPF37O. Accessed October 16, 2018.

3. Miller AE, Wolinsky JS, Kappos L, et al. Oral teriflunomide for patients with a first clinical episode suggestive of multiple sclerosis (TOPIC): a randomised

, double-blind, placebo-controlled, phase 3 trial. Lancet Neurol. 2014 (10):977-86.


: 10.1016/S1474-4422(14)70191.