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DOI: 10.1055/a-2365-0966
Ofatumumab in der Behandlung der Multiplen Sklerose – Eine Übersicht der präklinischen und klinischen Daten
Ofatumumab in the treatment of multiple sclerosis – A summary of preclinical and clinical data Fördermittel Die redaktionelle Unterstützung und die grafische Ausarbeitung wurden finanziert von der Novartis Pharma GmbH.
Zusammenfassung
Hintergrund B-Zell-gerichtete Therapien sind hochwirksam bei Multipler Sklerose (MS). Die meisten dieser Therapien sind in langen Intervallen intravenös zu applizieren. Seit 2021 ist aber auch Ofatumumab zur Behandlung der MS zugelassen, ein Anti-CD20-Antikörper, der aufgrund hoher Affinität zur Zielstruktur niedrig dosiert und monatlich subkutan verabreicht wird.
Methoden Es wird eine Übersicht über aktuelle praxisrelevante immunologische und klinische Daten zu Ofatumumab gegeben.
Ergebnisse Die hohe Affinität von Ofatumumab zur Zielstruktur erlaubt eine niedrige Dosierung in kleinem Volumen, wobei das Freisetzungs- und Resorptionsverhalten nach subkutaner Applikation hohe Konzentrationen in den Lymphknoten und eine graduelle B-Zell-Depletion ermöglicht. Ein schneller Wirkeintritt ist ebenso gegeben wie eine B-Zell-Repletion innerhalb weniger Monate bei Therapieabbruch. Langzeitdaten zeigen über bis zu vier Jahre stabile IgG-Spiegel und eine nachhaltig hohe Wirksamkeit hinsichtlich Schubrate, Progression und Kognition, wobei der Vorteil gegenüber Teriflunomid in den klinischen Studien größer war, je früher die Therapie begonnen wurde. Ofatumumab zeigt ein spezifisches B-Zell-Depletionsmuster. CD20-exprimierende B-Zell-Vorläuferzellen im Knochenmark bleiben erhalten und damit auch die Induzierbarkeit und Ausdifferenzierung von Plasmazellen. Die Ausbildung eines humoralen immunologischen Gedächtnisses ist daher möglich. Vierjahres-Studiendaten zeigten keine Auffälligkeiten in der Rate schwerer Infektionen oder maligner Erkrankungen.
Schlussfolgerung Ofatumumab ist eine innovative B-Zell-gerichtete Therapie. Es ist hochwirksam bei guter Sicherheit und Verträglichkeit und gut steuerbar bei erhaltener Immunkompetenz gegenüber Pathogenen.
Abstract
Background B-cell targeted therapies are highly effective in multiple sclerosis (MS). Most of these therapies are administered intravenously at long intervals. Ofatumumab, an anti-CD20 antibody that is administered subcutaneously at low doses on a monthly basis due to its high affinity to the target structure, became available for the treatment of MS in 2021.
Methods An overview of practice-relevant immunological and clinical data on ofatumumab is provided.
Results The high affinity of ofatumumab to the target structure allows low dose and low volume administration, with the release and absorption profile after subcutaneous application allowing for high concentrations in the lymph nodes and gradual depletion of B-cells. Rapid onset of action is achieved as well as B-cell repletion within a few months in case of discontinuation of therapy. Long-term data show stable IgG levels over up to four years and high efficacy with respect to relapse rate, progression, and cognition. According to current study data, the effect compared to teriflunomide is greater the earlier therapy is initiated. Ofatumumab has a specific B-cell depletion pattern. CD20 expressing B-cell progenitor cells in the bone marrow are preserved and therefore also the inducibility and differentiation of plasma cells. The formation of a humoral immunological memory is therefore possible. Four-year study data showed no abnormalities in the rate of severe infections or malignancies.
Conclusions Ofatumumab is an innovative B-cell targeted therapy. It is highly effective with a good safety and tolerability profile, well controllable and maintains immunocompetence against pathogens.
Publikationsverlauf
Eingereicht: 24. Januar 2024
Angenommen nach Revision: 27. Juni 2024
Artikel online veröffentlicht:
19. August 2024
© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).
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