Frequency of Infection Doesn't Fluctuate with Teriflunomide Treatment

In the Multiple Sclerosis Treatment Safety poster session at the American Academy of Neurology (AAN) 2013 Annual Meeting, Barry Singer, a neurologist at the Missouri Baptist Medical Center, in St. Louis, and founder and director of the MS Center for Innovations in Care, and his co-authors presented an analysis of infection rates in three placebo-controlled teriflunomide studies.

Teriflunomide is a novel, once-daily oral immunomodulatory therapy recently approved in the U.S. for relapsing multiple sclerosis (RMS). The treatment inhibits pyrimidine synthesis and limits the expansion of stimulated T and B cells while appearing to preserve resting lymphocyte function.

The objectives of the retrospective analysis were to explore the rate of infections and changes in white blood cell (WBC) counts throughout teriflunomide treatment. Safety data were pooled from three placebo-controlled teriflunomide trials — one phase 2 study and two phase 3 studies. RMS patients received a once-daily, 14-milligram oral teriflunomide dose (n=786), 7-milligram teriflunomide dose (n=838) or placebo (n=806) for 36 weeks (NCT01487096), 108 weeks (NCT00134563, TEMSO), or 48 to 152 weeks (NCT00751881, TOWER).

The frequency of infections was similar between groups, while the relative risk of infection did not increase with either dosage strength of teriflunomide versus placebo. Serious infections occurred infrequently and with similar incidences across groups. However, two fatal infections occurred — bacterial sepsis in the 14-milligram teriflunomide group and respiratory infection in the placebo group — and four serious, opportunistic infections were reported: cytomegalovirus (CMV) hepatitis and gastrointestinal tuberculosis in the 14-milligram teriflunomide group; herpes zoster and hepatitis C with CMV in the placebo group. No cases of progressive multifocal leukoencephalopathy occurred.

Hematologic laboratory data showed decreases in mean WBC counts in the teriflunomide-treated groups of about 15 percent or less, primarily of neutrophils and lymphocytes. Those decreases occurred during the first six weeks and remained stable during treatment. There was no evidence of a link between decrease in WBC and the occurrence of infections.

In summary, teriflunomide treatment for RMS showed a low incidence of serious infections, which was not significantly different from placebo intake. Mean reductions in WBC counts were small in magnitude, often stabilized during treatment and not associated with infections. The findings provided evidence that risk of infection is not increased by teriflunomide treatment.