Hematological Alterations Related to Treatment with Teriflunomide and Dimethyl Fumarate in Multiple Sclerosis

Daniel Apolinar García-Estévez

doi:10.3390/neurosci1010003

Abstract

The exact mechanism of action of different modifying treatments in the evolutionary course of multiple sclerosis (MS) remains unknown, but it is assumed that they act upon the cells involved in acquired immunity. One effect of these treatments is the development of lymphopenia, which carries inherent safety risks. This study was conducted to understand the alterations that teriflunomide (TERI) and dimethyl fumarate (DMF) exert upon white blood cells in a series of patients with MS. This study included a total of 99 patients; 44 treated with DMF and 55 patients treated with TERI. Blood counts were evaluated at baseline and every 6 months in order to track the absolute leukocyte, lymphocyte, and neutrophil counts. Twelve months after starting treatment, we observed a significant decrease in leukocytes (21.1%), lymphocytes (39.1%), and neutrophils (10%) in the DMF group. In the TERI group, leukocytes decreased by 11.1%, lymphocytes by 8.1%, and neutrophils by 15.7%. Both TERI and DMF produced a significant decrease in leukocytes during the first year of treatment and this was mainly related with a decrease in neutrophils in the TERI group and a decrease in lymphocytes in the DMF group.

Highlights

Multiple Sclerosis (MS) is a demyelinating inflammatory disease of the central nervous system (CNS) with an autoimmune etiopathogenesis which involves both innate immunity and acquired immunity directed towards a specific antigen (B and T lymphocytes and natural killer cells)
Both TERI and Dimethyl fumarate (DMF) produced a significant decrease in leukocytes during the first year of treatment and this was mainly related with a decrease in neutrophils in the TERI group and a decrease in lymphocytes in the DMF group
A total of 99 patients were included in this study; 55 were treated with TERI and 44 received treatment with DMF

Summary

Introduction

Multiple Sclerosis (MS) is a demyelinating inflammatory disease of the central nervous system (CNS) with an autoimmune etiopathogenesis which involves both innate immunity (monocytes, neutrophils, macrophages, and dendritic cells) and acquired immunity directed towards a specific antigen (B and T lymphocytes and natural killer cells). T and B cells, resulting in a 15% decrease in the white blood cell count (especially lymphocytes and neutrophils), which usually occurs in the third month of treatment but subsequently remains stable [4,5]. Dimethyl fumarate (DMF) reduces the percentage of T cells and of every B cell population type present in peripheral blood. Regarding the effects of DMF on T lymphocytes, it disproportionately decreases CD8+ lymphocytes compared to CD4+ lymphocytes, which translates into an increase in the CD4/CD8 ratio [4,5]

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Conclusion