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Methotrexat in der Rheumatologie

Methotrexate in rheumatology

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Zusammenfassung

Der Folsäureantagonist Methotrexat (MTX) hat über die letzten Jahrzehnte insbesondere in der Therapie der rheumatoiden Arthritis (RA) eine überragende Rolle erlangt. MTX ist bei der RA nicht nur Disease Modifying Anti-Rheumatic Drug der ersten Wahl, eine Vielzahl von randomisierten klinischen Studien zeigt darüber hinaus, dass es auch ein notwendiger Kombinationspartner ist, um eine optimale Wirkung von Biologika zu erreichen. MTX ist daher der zentrale Pfeiler der medikamentösen Therapie der RA. Alle Untersuchungen haben immer wieder die gute Sicherheit des Medikaments auch bei Langzeiteinnahme belegt. In weiteren Indikationen der Rheumatologie hat sich MTX fest etabliert. Die Wirkungsweise von MTX in der Entzündung ist komplex, wird aber zunehmend besser verstanden. Erste Ansätze zur Vorhersage der Wirkung und Verträglichkeit von MTX mit Hilfe der Analyse von genetischen Polymorphismen wurden beschrieben. MTX-Konjugate, welche endogenes Albumin als Trägermolekül in die Synovitis nutzen, wie auch neue rezeptorspezifische Folatantagonisten sind derzeit in präklinischer Testung. Das Ziel, das besonders erfolgreiche Therapieprinzip der Folatinhibition in der Behandlung rheumatischer Erkrankungen für die Zukunft weiterzuentwickeln, scheint erreichbar.

Abstract

Methotrexate (MTX) is a folate inhibitor which has gained a major role in the treatment of rheumatoid arthritis (RA). MTX is not only the disease modifying anti-rheumatic drug of first choice, a large number of clinical trials moreover show that biologic drugs should be combined with MTX in order to obtain optimal therapeutic efficacy. Therefore, MTX is an anchor drug for the treatment of RA. Large studies show the general safety of the drug for long term treatment. The mechanisms of action of MTX in inflammation are complex but increasingly better understood. Current publications show that first steps have been done towards prediction of therapeutic response and toxicity of MTX by analysis of gene polymorphism. Conjugates of MTX which use endogenous albumin as a drug carrier to synovitis as well as new receptor-specific folate inhibitors are currently tested in pre-clinic investigations. The goal to further develop the most successful principle of folate inhibition for the treatment of rheumatic diseases seems to be feasible.

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Der korrespondierende Autor weist auf folgende Beziehungen hin:

Der Autor ist immer wieder als Referent oder Autor tätig und erhält dafür auch Honorare von pharmazeutischen Firmen, welche hier besprochene Substanzen vertreiben: z. B. Medac GmbH, Wyeth u.a.

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    C. Fiehn

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Fiehn, C. Methotrexat in der Rheumatologie. Z. Rheumatol. 68, 747–757 (2009). https://doi.org/10.1007/s00393-009-0535-2

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