Randomized study of teriflunomide effects on immune responses to neoantigen and recall antigens

Abstract

Objective:To evaluate immune responses to neoantigen and recall antigens in healthy subjects treated with teriflunomide.Methods:This was a randomized, double-blind, placebo-controlled study. Subjects received oral teriflunomide (70 mg once daily for 5 days followed by 14 mg once daily for 25 days) or placebo for 30 days. Antibody responses were evaluated following rabies vaccination (neoantigen) applied at days 5, 12, and 31 of the treatment period. Occurrence of delayed-type hypersensitivity (DTH) to Candida albicans, Trichophyton, and tuberculin (recall antigens) was assessed before and at the end of treatment to investigate cellular memory response. Safety and pharmacokinetics were evaluated.Results:Forty-six randomized subjects were treated (teriflunomide, n = 23; placebo, n = 23) and completed the rabies vaccination. Geometric mean titers for rabies antibodies were lower with teriflunomide at days 31 and 38 than with placebo. However, all subjects achieved sufficient seroprotection following rabies vaccination (titers well above the 0.5 IU/mL threshold). Overall, the DTH response to recall antigens in the teriflunomide group did not notably differ from responses in the placebo group.Conclusions:Following vaccination, geometric mean titers for rabies antibodies were lower with teriflunomide than with placebo. However, teriflunomide did not limit the ability to achieve seroprotective titers against this neoantigen. Evaluation of DTH showed that teriflunomide had no adverse impact on the cellular memory response to recall antigens.Classification of evidence:This study provides Class II evidence that in normal subjects treated with teriflunomide, antibody titer responses to rabies vaccination are lower than with placebo but sufficient for seroprotection.

Teriflunomide treatment for multiple sclerosis modulates T cell mitochondrial respiration with affinity-dependent effects

“…Both preclinical data and data sets from clinical trials illustrate the impact of pharmacological DHODH inhibition on lymphocyte proliferation and expansion (7)(8)(9). However, as illustrated by a recently published placebocontrolled trial (10), it is still poorly understood how these drugs exert a selective effect on autoreactive T cells while only slightly affecting immune responses against bacteria and viruses. Although antibody titers for de novo immune responses were slightly impaired in this study, they were sufficient for seroprotection, while cellular memory responses to recall antigens were not affected.…”

COVID-19 in Teriflunomide-Treated Patients with Multiple Sclerosis

“…Furthermore, as we look to the future availability of a vaccine against SARS-CoV-2, it is also helpful to note that teri unomide-treated patients with MS generally developed effective immunity to seasonal in uenza and rabies after these vaccinations [23,24].…”

From Leflunomide to Teriflunomide: Drug Development and Immunosuppressive Oral Drugs in the Treatment of Multiple Sclerosis

“…Following this procedure, steady-state serum levels of at least 39.1 µg/ml are achieved after 6 days. In the same study, Teriflunomide was still detectable at more than 30 µg/ml after drug withdrawal of 8 days [ 66 ]. The half-life is long with around 18-19 days, and serum-levels decrease below levels of 0.02 µg/ml after 8 months of treatment discontinuation if no rapid elimination procedure is performed.…”