Safety Profile of Teriflunomide to Treat MS

Philadelphia—An analysis of data from clinical trials that evaluated the use of teriflunomide to treat multiple sclerosis (MS) found the oral drug had a manageable safety profile. The authors noted that the safety outcomes were similar for once-daily doses of 7 mg and 14 mg. However, the 14 mg dose was more effective in treating the disease.

Results were presented at the AAN meeting during a poster session titled Pooled Safety Data from Four Placebo-Controlled Teriflunomide Studies.

The FDA approved teriflunomide in September 2012 to treat relapsing-remitting MS. It is 1 of 3 oral medications for MS, with the others including fingolimod (approved in September 2010) and dimethyl fumarate (approved in March 2013).

In 2 previous studies, patients who received 14 mg teriflunomide achieved superior outcomes compared with a placebo group. The annualized relapse rates were 31.5% and 36.3% lower for patients taking 14 mg teriflunomide, while the confirmed disability progression sustained for 12 weeks was decreased by 29.8% and 31.5% in the 14 mg teriflunomide group. In addition, compared with the placebo group, patients who received 7 mg teriflunomide reduced the annualized relapse rates by 31.2% and 22.3%.

This analysis included data from 4 randomized, placebo-controlled, double-blind studies. Patients were randomized to receive 7 mg teriflunomide, 14 mg teriflunomide, or placebo for 36 weeks, 108 weeks, or 48 weeks after the last patient was randomized.
There were 1002 patients in the 14 mg teriflunomide group, 1045 patients in the 7 mg teriflunomide group, and 997 patients in the placebo group. Of the patients, 91.1% were white and 71% were female.

Treatment-emergent adverse events were found in 88.3% of patients in the 14 mg teriflunomide group, 85.6% of patients in the 7 mg teriflunomide group, and 85.6% of patients in the placebo group, while serious treatment-emergent adverse events were found in 13.3%, 12%, and 11.9% of patients, respectively. Treatment-emergent adverse events that led to discontinuation of the medications were found in 12.5%, 11.2%, and 7.5% of patients, respectively. Approximately 85% of the adverse events in each group were mild or moderate.

Common treatment-emergent adverse events that were more frequent in the teriflunomide groups included hair thinning, diarrhea, alanine aminotransferase (ALT) elevation, nausea, and headache. ALT elevation was the most common adverse event that led to treatment discontinuation in each group: 2.6% of patients in the 14 mg teriflunomide group, 3.3% of patients in the 7 mg teriflunomide group, and 2.3% of patients in the placebo group. There were 5 deaths, but none were related to teriflunomide treatment.

The authors also mentioned that transient, asymptomatic increases in ALT levels were more frequent in the teriflunomide groups: 21.5% of patients in the 14 mg teriflunomide group, 19.8% of patients in the 7 mg teriflunomide group, and 15.2% of patients in the placebo group. Serious infections were found in 2.7%, 2.2%, and 2.3% of patients, respectively. There was also no increased risk of malignancies among patients taking teriflunomide, according to the authors. They noted that there were 5 medically confirmed malignant tumors: 1 in the 14 mg teriflunomide group and 4 in the placebo group.

Furthermore, nearly all of the gastrointestinal disorders were mild to moderate in nature. Nausea was found in 10.7% of patients in the 14 mg teriflunomide group, 8% of patients in the 7 mg teriflunomide group, and 7.2% of patients in the placebo group, while 13.6%, 13.2%, and 7.6% of patients, respectively, had diarrhea.—Tim Casey

This study was funded by Genzyme.