Anti-Drug-Antikörper und der Einfluss von Methotrexat und Biologika-Applikationsintervall

Zusammenfassung

Anti-Drug-Antikörper (ADAbs) können die Therapieeffektivität biologischer krankheitsmodifizierender Antirheumatika (bDMARD) bei entzündlichen Arthropathien erheblich mindern. Mögliche ADAb-bedingte Probleme beinhalten u. a. einen sekundären Wirkverlust, einen rascheren Abbau des bDMARD und eine höhere Wahrscheinlichkeit für Hypersensitivitätsreaktionen. Das Risiko für die Bildung von ADAbs unterliegt vielen Einflussfaktoren und unterscheidet sich stark zwischen verschiedenen bDMARD. Generell besteht ein hohes Risiko besonders bei monoklonalen Antikörpern (MAbs), die gegen TNF gerichtet sind und ist niedriger bei MAbs, die nicht gegen TNF gerichtet sind und bei Fusionsproteinen. Eine begleitende Therapie mit MTX und anderen konventionell synthetischen (cs)DMARD mindert das Risiko der ADA-Bildung um etwa 2 Drittel bis 3 Viertel. Längere Intervalle zwischen den Dosen der MAbs und auch eine niedrige MAb-Dosis könnten die ADAb-Bildung erhöhen, basierend auf der Diskontinuitätstheorie der Immunität. Die Bildung von ADAbs stellt einen komplexen immunologischen Prozess dar, der durch spezifische Epitope, Proteinstruktur, patientenspezifische Faktoren und Applikationsbedingungen beeinflusst wird. Nicht neutralisierende ADAbs können die Pharmakokinetik und Nebenwirkungen des Medikaments beeinflussen, während neutralisierende ADAbs zusätzlich direkt die Wirksamkeit des bDMARD inhibieren können. Therapeutisches Drug-Monitoring (TDM) ist eine Option, um Medikamentenspiegel zu überwachen und ggf. die Dosierung anzupassen, um die langfristige Wirksamkeit der Therapie zu sichern. Die klinische Relevanz von ADAbs, insbesondere bei Anti-TNF-MAbs, und Strategien zur Minimierung ihrer Bildung werden im Detail erörtert.

Abstract

Anti-drug antibodies (ADAbs) can significantly reduce the therapeutic efficacy of biological disease-modifying antirheumatic drugs (bDMARDs) in inflammatory arthropathies. Possible ADAb-related problems include secondary loss of efficacy, more rapid degradation of the bDMARD, and a higher likelihood of hypersensitivity reactions. The risk of ADAb formation is influenced by many factors and varies greatly between different bDMARDs. In general, the risk is particularly high for monoclonal antibodies (MAbs) that target TNF and lower for MAbs that do not target TNF and for fusion proteins. Concomitant therapy with MTX and other conventional synthetic (cs)DMARDs reduces the risk of ADA formation by about 2 thirds to 3 quarters. Longer intervals between MAb doses and low MAb doses could increase ADAb formation, based on the discontinuity theory of immunity. The formation of ADAs is a complex immunological process that is influenced by specific epitopes, protein structure, patient-specific factors and application conditions. Non-neutralizing ADAs can influence the pharmacokinetics and side effects of the drug, while neutralizing ADAs can also directly inhibit the efficacy of the bDMARD. Therapeutic drug monitoring (TDM) is an option for monitoring drug levels and, if necessary, adjusting the dosage to ensure the long-term efficacy of the therapy. The clinical relevance of ADBs, especially in anti-TNF MAbs, and strategies to minimize their formation are discussed in detail.

Schlüsselwörter

Immunogenität - Methotrexat (MTX) - Biologika - Dosierungsintervall - Therapeutisches Drug-Monitoring (TDM)

Keywords

Immunogenicity - methotrexate (MTX) - biologics - dosing interval - therapeutic drug monitoring (TDM)

Publikationsverlauf

Artikel online veröffentlicht:
04. Dezember 2025

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