Influenza Vaccination Response Unaltered in Teriflunomide-Treated Multiple Sclerosis Patients

In the Multiple Sclerosis Treatment Safety poster session at the American Academy of Neurology (AAN) 2013 Annual Meeting, Paul O’Connor, of St. Michael's Hospital, in Toronto, and his colleagues presented a study designed to determine whether immune responses to seasonal influenza vaccination are preserved in teriflunomide-treated patients with relapsing forms of multiple sclerosis (RMS).

Teriflunomide is a once-daily, oral, disease-modifying therapy approved in the U.S. in September 2012 for the treatment of RMS. The drug inhibits the mitochondrial enzyme, DHODH — which is required for de novo pyrimidine synthesis — thereby reducing the proliferation of stimulated T and B cells. Cells that rely largely on existing pyrimidine pools, such as resting lymphocytes, are not significantly affected by exposure to teriflunomide.

In the previous TEMSO trial led by O’Connor, the incidence of infections, including influenza, was observed to be slightly higher in patients receiving teriflunomide than in those taking placebo. This raised some concern, since serious infections have occurred in rheumatoid arthritis patients taking leflunomide, which is another pyrimidine synthesis inhibitor.

In the non-randomized, multinational TERIVA trial presented at the poster session, the primary objective was to assess the antibody response to influenza vaccine in RMS patients treated with oral teriflunomide at two different doses — 7 milligrams and 14 milligrams — compared to a reference population defined as MS patients on a stable dose of interferon beta-1 (INF beta-1) for at least six months.

The study subjects were RMS patients treated with either 7-milligram (n=41) or 14-milligram (n=41) oral teriflunomide for a median duration of 5.7 years, as well as a reference population of RMS patients treated with INF β-1 (n=46) for the same median duration. Antibody responses to the 2011-2012 seasonal influenza vaccine — including strains H1N1, H3N2, and B, considered as a recall antigen in most patients — were assessed. The primary endpoint was the proportion of patients with seroprotective influenza antibody titers ≥40, 28 days post-vaccination, for each vaccine strain.

The proportion of patients meeting the primary endpoint following vaccination was >90% for H1N1 and B strains in all treatment groups, ≥90% for the H3N2 strain in the 7-milligram teriflunomide and IFNβ-1 groups, and 77% for H3N2 in the 14-milligram teriflunomide group. As influenza vaccination was well tolerated in all groups, O’Connor and his co-authors concluded that teriflunomide-treated patients mount effective immune responses to seasonal influenza vaccination, suggesting that the RMS treatment does not significantly affect responses to the vaccine.