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Review
. 2024 Apr;271(4):1515-1535.
doi: 10.1007/s00415-023-12007-3. Epub 2023 Oct 31.

Key characteristics of anti-CD20 monoclonal antibodies and clinical implications for multiple sclerosis treatment

Silvia R Delgado  1 , Simon Faissner  2 , Ralf A Linker  3 , Kottil Rammohan  4
Affiliations
Review

Key characteristics of anti-CD20 monoclonal antibodies and clinical implications for multiple sclerosis treatment

Silvia R Delgado et al. J Neurol. 2024 Apr.

Abstract

The recent success of anti-CD20 monoclonal antibody therapies in the treatment of multiple sclerosis (MS) has highlighted the role of B cells in the pathogenesis of MS. In people with MS, the inflammatory characteristics of B-cell activity are elevated, leading to increased pro-inflammatory cytokine release, diminished anti-inflammatory cytokine production and an accumulation of pathogenic B cells in the cerebrospinal fluid. Rituximab, ocrelizumab, ofatumumab, ublituximab and BCD-132 are anti-CD20 therapies that are either undergoing clinical development, or have been approved, for the treatment of MS. Despite CD20 being a common target for these therapies, differences have been reported in their mechanistic, pharmacological and clinical characteristics, which may have substantial clinical implications. This narrative review explores key characteristics of these therapies. By using clinical trial data and real-world evidence, we discuss their mechanisms of action, routes of administration, efficacy (in relation to B-cell kinetics), safety, tolerability and convenience of use. Clinicians, alongside patients and their families, should consider the aspects discussed in this review as part of shared decision-making discussions to improve outcomes and health-related quality of life for people living with MS.

Keywords: Anti-CD20; Multiple sclerosis; Ocrelizumab; Ofatumumab; Rituximab; Ublituximab.

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Conflict of interest statement

SRD has received research grant funding (clinical trials) from EMD Serono and Novartis. SF has received speaker’s and/or scientific board honoraria and/or congress travel support from Academy 2, Biogen, BMS, Celgene, Genesis Pharma, Janssen, Merck, Novartis and Roche and grant support from DMSG, Lead Discovery Center GmbH, Novartis, Ruhr-University Bochum and Stiftung für therapeutische Forschung; none related to this manuscript. RAL has received speaker’s and/or scientific board honoraria from Biogen, BMS, Celgene, Janssen, Novartis and Roche and grant support from Biogen and Novartis; none related to this manuscript. KR has received honoraria for participation in advisory boards or serving as consultant from Alexion Pharmaceuticals, Biogen, EMD Serono, Genentech, Horizon, Novartis and TG Therapeutics. KR has served as the site PI or co-investigator for grants received to his institution from Alexion, EMD Serono, Genentech, Genzyme and TG Therapeutics.

Figures

Fig. 1
Fig. 1
Binding epitopes of anti-CD20 monoclonal antibodies approved for or under clinical investigation for use in MS [36, 41, 48]. The binding epitope of BCD-132 is not currently publicly available. Adapted from Fox et al. and Bar-Or et al. [36, 41]. CD cluster of differentiation, MS multiple sclerosis
Fig. 2
Fig. 2
Median number of weeks for B-cell repletion for ocrelizumab, ofatumumab and ublituximab. aRepletion defined as recovery of CD19+ B cells to above the LLN or returned to baseline levels [30, 31, 37, 96]. bData reflect overall B-cell repletion. LLN lower limit of normal
See this image and copyright information in PMC

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