Advancing Treatment in Pediatric Multiple Sclerosis: The Promise of B-Cell-Targeting Therapies

Abstract

Pediatric-onset multiple sclerosis (POMS) is a rare yet increasingly recognized demyelinating disease of the central nervous system, characterized by a highly inflammatory disease course and an elevated relapse rate compared to adult-onset MS (AOMS). Given the unique immunopathogenesis of POMS, recent therapeutic strategies have shifted toward early initiation of high-efficacy disease-modifying therapies (DMTs) to minimize irreversible neurological damage. Among these, B-cell-targeting therapies, particularly anti-CD20 monoclonal antibodies, have shown efficacy in adult MS and are emerging as promising candidates for POMS treatment. The present review summarizes the current knowledge of the role of B-cells in POMS pathophysiology and evaluates the therapeutic potential of anti-CD-20 agents. It also highlights ongoing clinical trials and future perspectives, including novel B-cell-directed approaches such as anti-CD19 therapies, Bruton's tyrosine kinase (BTK) inhibitors, and BAFF-targeting agents.

Keywords: Alemtuzumab; B-cells; BTKis; Ocrelizumab; Ofatumumb; Rituximab; pediatric-onset multiple sclerosis; rare demyelinating CNS diseases.

Figure 1

Schematic overview of the role of B-cells in multiple sclerosis. TNFα: tumor necrosis factor alpha; GM-CSF: granulocyte-macrophage colony-stimulating factor; OCBs: oligoclonal bands.

Figure 2

B-cell ontology and B-cell-targeting therapies for pediatric-onset and adult-onset multiple sclerosis treatment.

Figure 3

B-cell ontology and candidate B-cell-targeting therapies for adult-onset and pediatric-onset multiple sclerosis treatment.

Figure 4

Schematic overview of the role of Bruton’s tyrosine kinase and its inhibitors in multiple sclerosis.