A Milestone in Multiple Sclerosis Therapy: Monoclonal Antibodies Against CD20—Yet Progress Continues

Multiple sclerosis (MS), which is a chronic inflammatory disease of the central nervous system, still represents one of the most common causes of persisting disability with an early disease onset. Growing evidence suggests B cells to play a crucial role in its pathogenesis and progression. Over the...

Full description

Saved in:
Bibliographic Details
Published in:Neurotherapeutics 2021-07, Vol.18 (3), p.1602-1622
Main Authors: Frisch, Esther S., Pretzsch, Roxanne, Weber, Martin S.
Format: Article
Language:English
Subjects:
Antibodies, Monoclonal - pharmacology
Antibodies, Monoclonal - therapeutic use
Antibodies, Monoclonal, Humanized - pharmacology
Antibodies, Monoclonal, Humanized - therapeutic use
Antigens, CD20 - immunology
B-Lymphocytes, Regulatory - drug effects
B-Lymphocytes, Regulatory - immunology
Biomedical and Life Sciences
Biomedicine
CD20 antigen
Central nervous system
Clinical Trials as Topic - methods
Current Perspectives
Current s
Humans
Immunosuppressive agents
Immunotherapy
Inflammatory diseases
Lymphocytes B
Monoclonal antibodies
Multiple sclerosis
Multiple Sclerosis - drug therapy
Multiple Sclerosis - immunology
Multiple Sclerosis, Chronic Progressive - drug therapy
Multiple Sclerosis, Chronic Progressive - immunology
Multiple Sclerosis, Relapsing-Remitting - drug therapy
Multiple Sclerosis, Relapsing-Remitting - immunology
Neurobiology
Neurology
Neurosciences
Neurosurgery
Pathogenesis
Rituximab
Rituximab - pharmacology
Rituximab - therapeutic use
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Multiple sclerosis (MS), which is a chronic inflammatory disease of the central nervous system, still represents one of the most common causes of persisting disability with an early disease onset. Growing evidence suggests B cells to play a crucial role in its pathogenesis and progression. Over the last decades, monoclonal antibodies (mabs) against the surface protein CD20 have been intensively studied as a B cell targeting therapy in relapsing MS (RMS) as well as primary progressive MS (PPMS). Pivotal studies on anti-CD20 therapy in RMS showed remarkable clinical and radiological effects, especially on acute inflammation and relapse biology. These results paved the way for further research on the implication of B cells in the pathogenesis of MS. Besides controlling relapse development in RMS, ocrelizumab (OCR) also showed clinical benefits in patients with PPMS and became the first approved drug for this disease course. In this review, we provide an overview of the current anti-CD20 mabs used or tested for the treatment of MS—namely rituximab (RTX), OCR, ofatumumab (OFA), and ublituximab (UB). Besides their effectiveness, we also discuss possible limitations and safety concerns especially in regard to long-term treatment, both for this class of drugs overall as well as for each anti-CD20 mab individually. Additionally, we elucidate to what extent anti-CD20 therapy may alter the function of other immune cells, both directly or indirectly. Finally, we cover the current knowledge on repopulation of CD20 + cells after cessation of anti-CD20 treatment and discuss future aspirations towards alternative, further developed B cell silencing therapies.
ISSN:1933-7213
1878-7479
1878-7479
DOI:10.1007/s13311-021-01048-z