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Role of oral teriflunomide in the management of multiple sclerosis.

ABSTRACT: The landscape of the treatment of relapsing-remitting multiple sclerosis is changing fast. Several oral treatments have shown benefit and generate much interest because of the convenience of their administration. Two oral compounds, fingolimod and teriflunomide, have been approved in relapsing-remitting multiple sclerosis, while others have completed Phase III trials and are awaiting review for registration. Teriflunomide is a pyrimidine synthesis inhibitor with selective immunomodulatory and immunosuppressive properties that have shown consistent efficacy in clinical trials, and a good safety profile. This paper provides an overview of the mechanisms of action and efficacy and safety results from clinical trials with this drug. The role of teriflunomide in the treatment of relapsing-remitting multiple sclerosis is discussed.

SUBMITTER: Tanasescu R

PROVIDER: S-EPMC3639219 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Role of oral teriflunomide in the management of multiple sclerosis.

Tanasescu Radu R Evangelou Nikos N Constantinescu Cris S CS

Neuropsychiatric disease and treatment 20130422

The landscape of the treatment of relapsing-remitting multiple sclerosis is changing fast. Several oral treatments have shown benefit and generate much interest because of the convenience of their administration. Two oral compounds, fingolimod and teriflunomide, have been approved in relapsing-remitting multiple sclerosis, while others have completed Phase III trials and are awaiting review for registration. Teriflunomide is a pyrimidine synthesis inhibitor with selective immunomodulatory and im ...[more]

PMID: 23637535

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| S-EPMC3573676 | biostudies-literature

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Project description:Background and objectivesInhibition of de novo pyrimidine synthesis in proliferating T and B lymphocytes by teriflunomide, a pharmacological inhibitor of dihydroorotate dehydrogenase (DHODH), has been shown to be an effective therapy to treat patients with MS in placebo-controlled phase 3 trials. Nevertheless, the underlying mechanism contributing to the efficacy of DHODH inhibition has been only partially elucidated. Here, we aimed to determine the impact of teriflunomide on the immune compartment in a longitudinal high-dimensional follow-up of patients with relapse-remitting MS (RRMS) treated with teriflunomide.MethodsHigh-dimensional spectral flow cytometry was used to analyze the phenotype and the function of innate and adaptive immune system of patients with RRMS before and 12 months after teriflunomide treatment. In addition, we assessed the impact of teriflunomide on the migration of memory CD8 T cells in patients with RRMS, and we defined patient immune metabolic profiles.ResultsWe found that 12 months of treatment with teriflunomide in patients with RRMS does not affect the B cell or CD4 T cell compartments, including regulatory TREG follicular helper TFH cell and helper TH cell subsets. In contrast, we observed a specific impact of teriflunomide on the CD8 T cell compartment, which was characterized by decreased homeostatic proliferation and reduced production of TNFα and IFNγ. Furthermore, we showed that DHODH inhibition also had a negative impact on the migratory velocity of memory CD8 T cells in patients with RRMS. Finally, we showed that the susceptibility of memory CD8 T cells to DHODH inhibition was not related to impaired metabolism.DiscussionOverall, these findings demonstrate that the clinical efficacy of teriflunomide results partially in the specific susceptibility of memory CD8 T cells to DHODH inhibition in patients with RRMS and strengthens active roles for these T cells in the pathophysiological process of MS.

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Teriflunomide treatment is associated with optic nerve recovery in early multiple sclerosis.

Project description:Background and aimsVarious attempts have been made to support recovery following optic neuritis (ON), but the respective trials have mostly been negative. The aim of this study was to determine whether disease-modifying treatment (DMT) following ON as first manifestation of relapsing-remitting multiple sclerosis influences long-term outcomes.MethodsA total of 79 patients with ON were identified and evaluated at relapse, DMT induction, and 12 months following treatment induction with either glatiramer acetate (GLAT), interferon-beta (IFN), or teriflunomide (TRF). Low-contrast letter acuity (LCLA) and full-field visual-evoked potentials (FF-VEP) were compared between treatment groups using multivariable regression models. The impact of TRF treatment induction compared with IFN or GLAT following relapses outside the optic nerves was evaluated in an independent cohort of 122 patients. Magnetic resonance imaging (MRI) outcomes and rates of confirmed improvement of relapse-related disability were evaluated.ResultsTRF-treated patients exhibited higher LCLA and lower relative P100 latencies normalized to the fellow-eye. Findings were significant following covariate-adjustment by multivariable analyses. Cranial MRI lesion load as well as disability progression rates were not significantly different between groups. The cohort of patients following relapses other than ON showed no differences in confirmed improvement of disability.ConclusionTRF treatment is associated with favorable outcomes regarding functional optic nerve recovery following ON in early multiple sclerosis.

| S-EPMC7940774 | biostudies-literature

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