Zeitschrift für Rheumatologie

, Volume 70, Issue 2, pp 101–107

Pharmakogenetik und Pharmakogenomik von Methotrexat

Aktuelle Bestandsaufnahme und neue Aspekte
Leitthema

Zusammenfassung

Seit seiner Einführung als Basistherapeutikum ist der Folsäureantagonist Methotrexat (MTX) eine tragende Säule antirheumatischer Therapie. Dies hat sich auch nach Einführung der neuen, auf rekombinanten Proteinen basierenden, „Biologicals“ nicht grundlegend geändert. Trotz eindrucksvoller Fortschritte zeigt auch heute annähernd jeder zweite Patient ein nur suboptimales Ansprechen auf Antirheumatika. Eine fehlende oder insuffiziente Wirksamkeit zeigt sich insbesondere bei etwa jedem vierten Patienten unter MTX und führt oftmals zum Absetzen des Medikaments. Hinzu kommen Nachjustierungen der Pharmakotherapie infolge von Unverträglichkeiten. Vor diesem Hintergrund und unter Berücksichtigung der zunehmenden Vereinfachung der Nutzung genetischer Analysen in der medizinischen Praxis ist die Erarbeitung von Strategien zur Umsetzung individualisierter Pharmakotherapie heute zentrales Forschungsfeld. Zahlreiche Studien der letzten Jahre analysierten in diesem Zusammenhang Genpolymorphismen zellulärer Parameter, die mit Wirkung und Toxizität von MTX in Beziehung stehen. Die bislang vorliegenden Resultate belegen gleichsam Potenzial und Limitationen des wichtigen Instruments der klinischen Genpolymorphismusanalyse.

Schlüsselworter

Methotrexat Rheumatoide Arthritis Genpolymorphismen Pharmakogenetik Pharmakogenomik 

Pharmacogenetics and pharmacogenomics of methotrexate

Current status and novel aspects

Abstract

Since its introduction as a disease-modifying drug, methotrexate (MTX), a folate antagonist, is regarded as a major pillar of anti-rheumatic pharmacotherapy. This has not been changed in the current era of biologicals based on recombinant proteins. Despite most promising therapeutic progress about half of rheumatoid arthritis patients still display insufficient response to anti-rheumatic drugs. Specifically, about one in four patients on MTX shows lack of sufficient therapeutic efficacy which may lead to drug discontinuation. In addition, adjustment of therapy may be necessary due to individual drug toxicity. In this context and in light of recent advances concerning the use of genetic analysis in clinical practice, the development of novel strategies which implement individualized pharmacotherapy has become a major issue for translational and clinical research. Accordingly, numerous studies have been performed in recent years analyzing genetic polymorphisms of cellular parameters which relate to MTX efficacy and toxicity. Data currently available demonstrate the potential and the limitations of clinical genetic polymorphism analyses.

Keywords

Methotrexate Rheumatoid arthritis Genetic polymorphisms Pharmacogenetics Pharmacogenomics 

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  1. 1.pharmazentrum frankfurtKlinikum der Goethe-Universität FrankfurtFrankfurt am MainDeutschland

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