Anti-CD20 monoclonal antibodies in multiple sclerosis

Over the past two decades, treatment options for patients with multiple sclerosis (MS) have increased exponentially. In the current therapeutic landscape, “no evidence of MS disease activity” is within reach in many of our patients. Minimizing risks of complications, improving treatment convenience, and decreasing health care costs are goals that are yet to be reached. One way to optimize MS therapy is to implement personalized or extended interval dosing. Monoclonal antibodies are suitable candidates for personalized dosing (by therapeutic drug monitoring) or extended interval dosing. An increasing number of studies are performed and underway reporting on altered dosing intervals of anti-α4β1-integrin treatment (natalizumab) and anti-CD20 treatment (ocrelizumab, rituximab, and ofatumumab) in MS. In this review, current available evidence regarding personalized and extended interval dosing of monoclonal antibodies in MS is discussed with recommendations for future research and clinical practice.

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Anti-CD20 Monoclonal Antibodies for Relapsing and Progressive Multiple Sclerosis

CNS Drugs ◽

10.1007/s40263-020-00704-w ◽

2020 ◽

Vol 34 (3) ◽

pp. 269-280 ◽

Cited By ~ 6

Author(s):

Finn Sellebjerg ◽

Morten Blinkenberg ◽

Per Soelberg Sorensen

Keyword(s):

Multiple Sclerosis ◽

Monoclonal Antibodies ◽

Progressive Multiple Sclerosis ◽

Anti Cd20

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

Neurotherapeutics ◽

10.1007/s13311-021-01048-z ◽

2021 ◽

Author(s):

Esther S. Frisch ◽

Roxanne Pretzsch ◽

Martin S. Weber

Keyword(s):

Multiple Sclerosis ◽

Monoclonal Antibodies ◽

B Cells ◽

B Cell ◽

Current Knowledge ◽

Disease Onset ◽

Chronic Inflammatory Disease ◽

Targeting Therapy ◽

Long Term Treatment ◽

Anti Cd20

AbstractMultiple 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.

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Impact of Disease-Modifying Treatments of Multiple Sclerosis on Anti–SARS-CoV-2 Antibodies

Neurology Neuroimmunology & Neuroinflammation ◽

10.1212/nxi.0000000000001055 ◽

2021 ◽

Vol 8 (5) ◽

pp. e1055

Author(s):

Kévin Bigaut ◽

Laurent Kremer ◽

Thibaut Fabacher ◽

Livia Lanotte ◽

Marie-Celine Fleury ◽

...

Keyword(s):

Multiple Sclerosis ◽

Monoclonal Antibodies ◽

Recurrent Infection ◽

Humoral Response ◽

Interferon Β ◽

Igg Index ◽

Disease Modifying ◽

Anti Cd20 ◽

Class Iv

ObjectiveTo compare the humoral response after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with multiple sclerosis (MS) receiving different disease-modifying treatments (DMTs).MethodsPatients with MS with coronavirus disease 2019 (COVID-19) and available anti–SARS-CoV-2 serology were included. The primary endpoint was the anti–SARS-CoV-2 immunoglobulin G (IgG) index. The multivariate analysis was adjusted for COVID-19 severity, SARS-CoV-2 PCR result, and the time between COVID-19 onset and the serology.ResultsWe included 61 patients with available IgG index. The IgG index was lower in patients with fingolimod or anti-CD20 monoclonal antibodies compared with patients without treatment (p < 0.01), patients with interferon β-1a or glatiramer (p < 0.01), and patients with another DMT (p = 0.01). The IgG index was correlated with the time between COVID-19 onset and serology (r = −0.296 [−0.510; −0.0477], p = 0.02).ConclusionsHumoral response after COVID-19 was lower in patients with MS with fingolimod or anti-CD20 mAb. These patients could therefore be at risk of recurrent infection and could benefit from anti–SARS-CoV-2 vaccination. The humoral response after vaccination and the delay before vaccination need to be evaluated.Classification of EvidenceThis study provides Class IV evidence that patients treated with fingolimod or anti-CD20 monoclonal antibodies for MS have a lower humoral response after COVID-19 compared with patients without DMTs or with another DMTs.

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The comparative efficacy and safety of anti-CD20 monoclonal antibodies for relapsing-remitting multiple sclerosis: A network meta-analysis

IBRO Neuroscience Reports ◽

10.1016/j.ibneur.2021.08.003 ◽

2021 ◽

Vol 11 ◽

pp. 103-111

Author(s):

Mohammad Z.I. Asha ◽

Yousef Al-Asaad ◽

Sundos F.H. Khalil

Keyword(s):

Multiple Sclerosis ◽

Monoclonal Antibodies ◽

Meta Analysis ◽

Efficacy And Safety ◽

Comparative Efficacy ◽

Relapsing Remitting ◽

Remitting Multiple Sclerosis ◽

Anti Cd20 ◽

Relapsing Remitting Multiple Sclerosis

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Impact of COVID-19 on multiple sclerosis care and management: Results from the European Committee for Treatment and Research in Multiple Sclerosis survey

Multiple Sclerosis Journal ◽

10.1177/13524585211005339 ◽

2021 ◽

pp. 135245852110053

Author(s):

Emilio Portaccio ◽

Mattia Fonderico ◽

Bernhard Hemmer ◽

Tobias Derfuss ◽

Bruno Stankoff ◽

...

Keyword(s):

Multiple Sclerosis ◽

Access To Care ◽

Online Survey ◽

Dimethyl Fumarate ◽

Standards Of Care ◽

Treatment Practices ◽

European Committee ◽

Disease Modifying Therapy ◽

Anti Cd20 ◽

The Impact

Background: The spread of Coronavirus disease-19 (COVID-19) poses unique challenges in the management of people with multiple sclerosis (PwMS). Objectives: To collect data about the impact of COVID-19 emergency on access to care for PwMS and on MS treatment practices. Methods: Between March and July 2020, the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) promoted an online survey covering patient access to care, management of relapses and visits, disease-modifying therapy (DMT) and experience with COVID-19. Results: Three-hundred and sixty neurologists from 52 countries (68% from Europe) completed the survey. 98% reported COVID-19-related restrictions. Telemedicine was adopted to overcome the limited access to care and was newly activated (73%) or widely implemented (17%). 70% reported changes in DMT management. Interferons and glatiramer were considered safe. Dimethyl fumarate, teriflunomide and fingolimod were considered safe except for patients developing lymphopenia. No modifications were considered for natalizumab in 64%, cladribine in 24%, anti-CD20 in 22% and alemtuzumab in 17%; 18% (for alemtuzumab and cladribine) and 43% (for anti-CD20) considered postponing treatment. Conclusion: The ECTRIMS survey highlighted the challenges in keeping standards of care in clinical practice. Telemedicine clearly needs to be implemented. Gathering data on DMT safety will remain crucial to inform treatment decisions.

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Antigenic modulation limits the effector cell mechanisms employed by type I anti-CD20 monoclonal antibodies

Blood ◽

10.1182/blood-2014-07-588376 ◽

2015 ◽

Vol 125 (12) ◽

pp. 1901-1909 ◽

Cited By ~ 43

Author(s):

Thomas R. W. Tipton ◽

Ali Roghanian ◽

Robert J. Oldham ◽

Matthew J. Carter ◽

Kerry L. Cox ◽

...

Keyword(s):

Monoclonal Antibodies ◽

Natural Killer Cell ◽

Natural Killer ◽

Effector Cell ◽

Killer Cell ◽

Type I ◽

Antigenic Modulation ◽

Effector Mechanism ◽

Key Points ◽

Anti Cd20

Key Points Antigenic modulation significantly impacts natural killer cell and macrophage ability to mediate Fc γ receptor-dependent killing. hIgG1 mAbs are unable to elicit natural killer–mediated ADCC in the mouse, supporting ADCP as the dominant effector mechanism.

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