ECTRIMS Congress 2013: COPENHAGEN -- Teriflunomide (Aubagio) significantly reduced the risk of clinically definite multiple sclerosis in patients who had suffered a first bout of symptoms, an academic researcher confirmed here.

Aaron Miller, MD, of Mount Sinai School of Medicine in New York City said that the study, called TOPIC, was the first to show that an oral agent can reduce the risk of progression in patients with clinically isolated syndrome. Similar results had been reported earlier for interferon-beta drugs and glatiramer acetate (Copaxone).



Among 618 patients with clinically isolated syndrome, some 24% of those assigned to 14 mg/day of teriflunomide subsequently were diagnosed with full-blown MS after a second attack during 2 years of treatment, compared with 36% in those assigned to placebo (P=0.009),

These topline results had been released in April by the drug's manufacturer, Genzyme-Sanofi, but without 95% confidence intervals and with no quantitative information on secondary outcomes or adverse events.

Those secondary outcome results included the following, as reported by Miller:

Total lesion volumes were stable by the study's end in the 14-mg group, and increased slightly with the lower dose.

Increased alanine aminotransferase levels (above three times the upper limit of normal), headache, hair thinning, diarrhea, paresthesias, and upper respiratory tract infections were each seen more commonly with teriflunomide at one or both doses relative to placebo.

Decreased neutrophils and total white blood cell count were also more common with teriflunomide, but Miller did not provide numerical data. He noted that neutrophil and leukocyte counts remained within the normal range despite the decreases, and that they mainly occurred in the first 3 months of treatment.

Serious infections appeared more common with the 14-mg dose -- occurring in seven patients compared with two and three in the placebo and 7-mg groups, respectively -- but Miller said that three of those infections in the high-dose group were appendicitis attacks.

Patients in the study were about two-thirds female and mostly in their late 20s and 30s, as is typical of patients experiencing first MS symptoms. They were initially enrolled during the first 60 days after the initial symptoms, but the protocol was later modified to allow enrollment within 90 days, Miller said.

Session co-moderator Eva Havrdova, MD, PhD, of Charles University in Prague, asked Miller after his presentation what he thought the role of teriflunomide in clinically isolated syndrome should be.

"I think teriflunomide offers a viable treatment option," he replied, adding that he expected other oral therapies to eventually show that they are effective in this population as well.

After the presentation, Havrdova told MedPage Today that she generally agreed with his assessment, but she noted that the drug carries a risk of birth defects for pregnant women.

"Two-thirds [of the TOPIC participants] were women and most of them were of child-bearing age," she noted. "I would be a little reluctant to offer the drug to women who plan pregnancy."

Teriflunomide won FDA approval a year ago for reducing relapse risk in adult patients with relapsing-remitting MS.

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