CMSC 2012: Oral Teriflunomide Not Superior to Interferon in Risk of Treatment Failure

SAN DIEGO — The oral disease-modifying drug under development for the treatment of relapsing-remitting multiple sclerosis (RRMS), teriflunomide, was not superior to interferon beta-1a (IFNbeta-1a) in risk of treatment failure, according to research presented at the Fourth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers (CMSC) and America’s Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).

Teriflunomide, the active metabolite of leflunomide, has been used in the treatment of rheumatoid arthritis since 1998. It works by blocking the proliferation and functioning of activated T and B lymphocytes by selecting inhibiting the critical mitochondrial enzyme, dihydro-orotate dehydrogenase (DHODH), which affects pyrimidine biosynthesis in quickly dividing lymphocytes but leaves the immune system’s response to infection uncompromised.

Patrick Vermersch, MD, of the University of Lille Norde de France in Lille, France, and colleagues conducted the 2-year, phase III TENERE study, a multicenter, randomized, parallel-group, rater-blinded study comparing the effectiveness and safety of teriflunomide 7 mg or 14 mg and subcutaneous IFNbeta-1a three times per week in 324 patients with RRMS. The primary endpoint was time to failure, which was defined as the first occurrence of confirmed relapse or permanent treatment discontinuation for any reason, whichever came first.

Overall, 48.6, 37.8, and 42.3% of patients failed treatment with teriflunomide 7 mg, 14 mg, and IFNbeta-1a, respectively. However, the rate of permanent treatment discontinuation was lower with teriflunomide (18.3 and 19.8%) than in the IFNbeta-1a group (28.8%).

The secondary endpoint, of annualized relapse rate (ARR) was not statistically significantly different for teriflunomide 14 mg compared with IFNbeta-1a (0.259 vs. 0.216, respectively), but teriflunomide 7 mg ARR was higher (0.410). At Week 48, treatment satisfaction was higher for both teriflunomide doses compared with IFNbeta-1a.

Both teriflunomide doses were well tolerated with no new or unexpected safety signals detected. Teriflunomide treatment was most commonly associated with nasopharyngitis, diarrhea, hair thinning, and back pain. IFNbeta-1a treatment was most commonly associated with alanine aminotransferase levels, headache, and flu-like symptoms. The rate of permanent treatment discontinuation in the study due to a treatment-emergent adverse event was higher in the IFNbeta-1a group compared with either teriflunomide dose (21.8 vs. 8.2 vs. 10.9%, respectively).

“No statistical superiority was observed when comparing the two teriflunomide groups and IFN-beta-1a on risk of failure, the primary composite endpoint. The rate of permanent treatment discontinuation was lower in both teriflunomide groups than in the IFN-beta-1a group. Both doses of teriflunomide were well tolerated,” the authors concluded.

This research was supported by Genzyme, a sanofi company.