Teriflunomide reduces annual relapse rate in patients with relapsing MS

In patients with relapsing forms of multiple sclerosis (MS), once-daily oral teriflunomide 14 mg significantly reduced the annual relapse rate and disability progressions, and improved several magnetic resonance imaging (MRI) measures of disease activity, including new or worsening brain lesions, according to a study published recently in The New England Journal of Medicine.

“This could be the first oral 'first-line' treatment for MS. It is safe and modestly effective, appropriate for many of the mild MS patients that we treat,” principal study investigator Paul O’Connor, MD, director of the MS Clinic at St. Michael’s Hospital, Toronto, Canada, told Formulary. He added that candidates include patients with relapsing MS who have had 1 or more attacks in the previous year or 2 in the previous 2 years.

Dr O’Connor and colleagues conducted a 2-year trial, called TEMSO (TEriflunomide Multiple Sclerosis Oral). The study included 1,088 patients aged 18 to 55 years with a score of 0 to 5.5 on the Expanded Disability Status Scale and at least 1 relapse in the previous year or at least 2 relapses in the previous 2 years. Patients were randomly assigned to either receive placebo, 7 mg of teriflunomide, or 14 mg of teriflunomide once daily for more than 2 years.

Resulting data demonstrated a significant reduction the risk of annual relapses by 31% (both P<.001) for both the 7-mg and 14-mg doses compared with placebo. Teriflunomide also significantly increased the time to first relapse, and allowed significantly more trial participants to remain free of relapses during the 2 years of the study: 53.7% (7 mg, P=.01 vs placebo), 56.5% (14 mg, P=.003 vs placebo) and 45.6% (placebo).

In addition, the risk of 12-week confirmed disability progression was significantly reduced by 30% (P=.03) for the 14-mg dose and numerically reduced by 24% (P=.08) for the 7-mg dose. When compared with placebo, teriflunomide improved several standard MRI measures of disease activity, including new or worsening brain lesions with an apparent dose dependent effect in favor of the 14-mg dose.

According to Dr O’Connor, there were no deaths or opportunistic infections, no effect on heart or airways, or macular edema. “This was not really surprising, as we had seen this in the phase 2; so I guess it was a pleasant surprise to see our phase 2 results confirmed in detail by a much larger study,” he said.

Teriflunomide was filed with FDA in August and the EMA filing is expected in the first quarter of 2012.