Biological Therapies in Multiple Sclerosis: Mechanisms of Action, Clinical Efficacy, and Safety of Monoclonal Antibodies Targeting CD20, CD52, and α4-Integrin - Review Article

ABSTRACT: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system driven by autoimmune mechanisms involving both T and B lymphocytes. Advances in immunopathological understanding have led to the development of highly effective biological therapies, particularly monoclonal antibodies targeting CD20, CD52, and α4-integrin. The aim of this study is to compare the mechanisms of action, clinical efficacy, and safety profiles of currently approved monoclonal antibodies used in MS treatment. Anti-CD20 therapies demonstrated robust efficacy in reducing relapse rates and MRI lesion activity across relapsing MS populations. Ocrelizumab showed additional efficacy in primary progressive MS by significantly slowing disability progression. Ublituximab provided comparable efficacy with shorter infusion times. Alemtuzumab exhibited high efficacy, particularly in early disease stages, but was associated with the highest rate of autoimmune and infectious adverse events. Natalizumab remained one of the most effective agents for relapse suppression; however, its long-term use was limited by the risk of progressive multifocal leukoencephalopathy (PML). Monoclonal antibodies have significantly improved MS outcomes, though their benefit–risk profiles vary. Anti-CD20 therapies offer the most favorable balance between efficacy and safety, while alemtuzumab and natalizumab require strict monitoring. Treatment selection should be individualized based on disease phenotype, safety considerations, and patient-specific factors. KEYWORDS: multiple sclerosis; monoclonal antibodies; CD20; CD52; α4-integrin; ocrelizumab; ofatumumab; ublituximab; alemtuzumab; natalizumab