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


METHODS
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.
Montreal Neurological Institute (A.B.-O.), McGill University, Montreal, Quebec, Canada; University of Münster (H.W.), Münster, Germany; Sanofi (B.M.), Bridgewater, NJ; Genzyme, a Sanofi company (M.B., P.T., F.M.-V.), Chilly-Mazarin, France; and Fishawack Communications, Inc. (M.C.), Horsham, PA.
Amit
A
Bar-Or
Montreal Neurological Institute (A.B.-O.), McGill University, Montreal, Quebec, Canada; University of Münster (H.W.), Münster, Germany; Sanofi (B.M.), Bridgewater, NJ; Genzyme, a Sanofi company (M.B., P.T., F.M.-V.), Chilly-Mazarin, France; and Fishawack Communications, Inc. (M.C.), Horsham, PA.
Heinz
H
Wiendl
Montreal Neurological Institute (A.B.-O.), McGill University, Montreal, Quebec, Canada; University of Münster (H.W.), Münster, Germany; Sanofi (B.M.), Bridgewater, NJ; Genzyme, a Sanofi company (M.B., P.T., F.M.-V.), Chilly-Mazarin, France; and Fishawack Communications, Inc. (M.C.), Horsham, PA.
Barry
B
Miller
Montreal Neurological Institute (A.B.-O.), McGill University, Montreal, Quebec, Canada; University of Münster (H.W.), Münster, Germany; Sanofi (B.M.), Bridgewater, NJ; Genzyme, a Sanofi company (M.B., P.T., F.M.-V.), Chilly-Mazarin, France; and Fishawack Communications, Inc. (M.C.), Horsham, PA.
Myriam
M
Benamor
Montreal Neurological Institute (A.B.-O.), McGill University, Montreal, Quebec, Canada; University of Münster (H.W.), Münster, Germany; Sanofi (B.M.), Bridgewater, NJ; Genzyme, a Sanofi company (M.B., P.T., F.M.-V.), Chilly-Mazarin, France; and Fishawack Communications, Inc. (M.C.), Horsham, PA.
Philippe
P
Truffinet
Montreal Neurological Institute (A.B.-O.), McGill University, Montreal, Quebec, Canada; University of Münster (H.W.), Münster, Germany; Sanofi (B.M.), Bridgewater, NJ; Genzyme, a Sanofi company (M.B., P.T., F.M.-V.), Chilly-Mazarin, France; and Fishawack Communications, Inc. (M.C.), Horsham, PA.
Meg
M
Church
Montreal Neurological Institute (A.B.-O.), McGill University, Montreal, Quebec, Canada; University of Münster (H.W.), Münster, Germany; Sanofi (B.M.), Bridgewater, NJ; Genzyme, a Sanofi company (M.B., P.T., F.M.-V.), Chilly-Mazarin, France; and Fishawack Communications, Inc. (M.C.), Horsham, PA.
Francoise
F
Menguy-Vacheron