B-cell–targeted therapies in relapsing forms of MS

Abstract

In recent years, there has been a significant increase in the therapeutic options available for the management of relapsing forms of MS. Therapies primarily targeting B cells, including therapeutic anti-CD20 monoclonal antibodies, have been evaluated in phase I, phase II, and phase III clinical trials. Results of these trials have shown their efficacy and relatively tolerable adverse effect profiles, suggesting a favorable benefit-to-risk ratio. In this review, we discuss the pathogenic role of B cells in MS and the rationale behind the utilization of B-cell depletion as a therapeutic cellular option. We also discuss the data of clinical trials for anti-CD20 antibodies in relapsing forms of MS and existing evidence for other B-cell–directed therapeutic strategies.

Transcriptome profiling of peripheral blood immune cell populations in multiple sclerosis patients before and during treatment with a sphingosine‐1‐phosphate receptor modulator

“…This reflects that the B cell subpopulations are sequestered to similar extents in lymphoid tissues. Basically, all treatments for MS modulate B cell subsets . Thus, further research on their roles in the pathogenesis of MS is of critical importance.…”

The role of B cells in multiple sclerosis: Current and future therapies

“…Presently there are 4 different anti-CD20 mAbs that have moved to phase III clinical trials for the treatment of RRMS: rituximab (RTX), ocrelizumab (OCR), ofatumumab (OFT), and ublituximab (UTX). In clinical trials, all four mAbs displayed similar efficacy and had favorable safety profiles, differing slightly in structure, target epitope, and predominant mechanism of B cell depletion 3,111,178 (Fig. 2b).…”

“…RTX-Rituximab is a mouse-human chimeric IgG1 mAb to CD20, depleting B cells primarily through CDC 3,178 . RTX was the first anti-CD20 mAb tested as a treatment for MS and, after yielding surprisingly promising results in its initial phase II clinical trial, provided the rationale for investigating anti-CD20 as an effective treatment for MS, RRMS specifically 111,173,178 .…”

“…RTX-Rituximab is a mouse-human chimeric IgG1 mAb to CD20, depleting B cells primarily through CDC 3,178 . RTX was the first anti-CD20 mAb tested as a treatment for MS and, after yielding surprisingly promising results in its initial phase II clinical trial, provided the rationale for investigating anti-CD20 as an effective treatment for MS, RRMS specifically 111,173,178 . In spite of the striking reduction in the number of new contrastenhancing lesions as well as relapse rates, RTX has not entered subsequent phase III clinical trials for various reasons and therefore is used as an off-label therapy for MS patients 173 .…”

The earlier the better

“…In addition to these studies, the November issue of Neurology: Neuroimmunology & Neuroinflammation contains a comprehensive review on B-cell-targeted therapies in relapsing forms of MS by Dubey et al, 9 and other interesting original articles that I hope will catch your attention. …”