Autoimmunity Center of Excellence

Author Of 1 Presentation

Disease Modifying Therapies – Mechanism of Action Late Breaking Abstracts

LB1267 - Teriflunomide Enhanced Innate and Adaptive Immune Regulatory Function in Treating Multiple Sclerosis (ID 2165)

Speakers
Presentation Number
LB1267
Presentation Topic
Disease Modifying Therapies – Mechanism of Action

Abstract

Background

The efficacy and safety of Teriflunomide (AubagioTM), a disease-modifying therapy (DMT) for relapsing multiple sclerosis (RMS) have been well established in pivotal trials. However, its mechanism of action on adaptive and innate immune cell compartments is yet to be elucidated.

Objectives

To report detailed immune phenotyping and immune cell function analysis from a prospective phase 4 study of relapsing MS patients receiving teriflunomide (NCT03464448).

Methods

27 subjects (age 18-65) were recruited from the University of Michigan MS Center who had been previously diagnosed with relapsing MS and were undergoing therapy with teriflunomide. Blood samples were collected for immunophenotyping and functional analysis. Peripheral blood mononuclear cells (PBMCs) were separated and stained with antibodies to examine cell subsets and analyzed by multicolor flow cytometry. Both adaptive and innate immune cell lineages at baseline pre-treatment and periodically for up to 2 years post teriflunomide treatment were studied.

Results

Teriflunomide treatment showed minimal effect on the frequencies and absolute counts of CD4+ T cells; it moderately reduced the frequency of CD8+ T cells, NK, and NKT cells. It significantly reduced the frequency NK cells, particularly pathogenic CD56dim NK cells, therefore reduced CD56dim/CD56hi ratio. Functional analysis revealed that NK cells from teriflunomide treated patients had increased trend of degranulation. In addition, teriflunomide also increased the expression CD39 and percentage of CD39+ Tregs, which implies an enhanced Treg suppressive function. Furthermore, teriflunomide decreased CXCR3 expression on T helper (Th) cells, which suggests impediment of pathogenic Th cells. Finally, teriflunomide showed a diminishing trend of the frequency of total B cells (specifically switched memory B cells) while it increased naïve B cells and downregulated the expression of co-stimulatory molecules CD80 and CD86.

Conclusions

In conclusion, teriflunomide promotes a tolerogenic immune response and suppresses the pathogenic immune response in relapsing MS patients.

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