Ofatumumab Modulates Inflammatory T Cell Responses and Migratory Potential in Patients With Multiple Sclerosis

Abstract

<h3>Background and Objectives</h3> The anti-CD20 antibody ofatumumab is an efficacious therapy for multiple sclerosis (MS) through depletion of B cells. The purpose of this study was to examine the derivative effects of B cell depletion on the peripheral immune system and a direct treatment effect on T cells expressing CD20. <h3>Methods</h3> Frequency and absolute numbers of peripheral leukocytes of treatment-naive patients with relapsing-remitting MS (RRMS) and patients treated with ofatumumab for a mean of 482 days were assessed in this observational study by flow cytometry. In addition, effector function and CNS migration of T cells using a human in vitro blood-brain barrier (BBB) assay were analyzed. <h3>Results</h3> This study showed that ofatumumab treatment of patients with RRMS increased the control of effector T cells and decreased T cell autoreactivity. It also showed that ofatumumab reduced the level of peripheral CD20⁺ T cells and that the observed decrease in CNS-migratory capacity of T cells was caused by the depletion of CD20⁺ T cells. Finally, our study pointed out a bias in the measurement of CD20⁺ cells due to a steric hindrance between the treatment antibody and the flow cytometry antibody. <h3>Discussion</h3> The substantial ofatumumab-induced alteration in the T cell compartment including a severely decreased CNS-migratory capacity of T cells could partly be attributed to the depletion of CD20⁺ T cells. Therefore, we propose that depletion of CD20⁺ T cells contributes to the positive treatment effect of ofatumumab and suggests that ofatumumab therapy should be considered a B cell and CD20⁺ T cell depletion therapy. <h3>Classification of Evidence</h3> This study provides Class IV evidence that compared with treatment-naive patients, ofatumumab treatment of patients with RRMS decreases peripheral CD20⁺ T cells, increases effector T cell control, and decreases T cell autoreactivity.