Evidenzbasierte Empfehlungen einer nationalen Expertenrunde zum Einsatz von Methotrexat bei entzündlich-rheumatischen Erkrankungen

Zusammenfassung

Hintergrund: Methotrexat (MTX) ist eines der am häufigsten eingesetzten Basistherapeutika bei rheumatischen Erkrankungen. In der klinischen Praxis und zahlreichen Therapiestudien ist MTX der Goldstandard für die Behandlung der rheumatoiden Arthritis. Dennoch hat eine Umfrage im Rahmen der internationalen 3e-Initiative (Evidence, Experts, Exchange) unter nationalen und internationalen Experten 10 unzureichend geklärte Fragen zur klinischen Anwendung von MTX erbracht. In diesem Projekt sollten daher evidenzbasierte Empfehlungen für die Anwendung von MTX erarbeitet werden. Die nationalen Empfehlungen der deutschen Expertengruppe werden hier vorgestellt.

Material und Methoden: Zwischen Januar und April 2007 wurden von Experten aus 17 Ländern 10 Fragen zur Anwendung von MTX formuliert. Zur Beantwortung der Fragen erfolgte bis Oktober 2007 durch „Multinational Fellows” eine systematische Literaturrecherche gemäß der aktualisierten Empfehlungen des Cochrane Instituts, deren Ergebnisse den nationalen Expertenrunden zur Verfügung gestellt wurden. Aus insgesamt 17 000 gefundenen Artikeln konnten nur 304 Arbeiten identifiziert werden, die zur Beantwortung der 10 Fragestellungen geeignet waren. Diese Arbeiten waren die Grundlage für die Erarbeitung der Expertenempfehlungen mittels eines Delphi-Verfahrens.

Ergebnisse: Die gestellten Fragen zu MTX wurden in die Themengruppen (A) Therapiestrategien, (B) Therapiesicherheit – Überwachung und Prävention und (C) Therapiesicherheit – Komplikationen eingeteilt. Auf den nationalen Treffen wurden unter der Leitung des wissenschaftlichen Komitees von 68 deutschen Rheumatologen interaktiv 10 Empfehlungen mit einem mittleren Grad der Annahme von 90% erarbeitet.

Schlussfolgerungen: Die 3e-Initiative hat aufgezeigt, dass hinsichtlich des praktischen Einsatzes von MTX bei rheumatischen Erkrankungen trotz langjähriger Erfahrung wichtige Fragen unzureichend geklärt sind. Die hier referierten evidenzbasierten Empfehlungen zu Anwendung, Therapieüberwachung und Management therapeutischer Komplikationen stellen einen nationalen Konsens erfahrener Experten dar, haben für die rheumatologische Praxis hohe Bedeutung und können als Basis zur Erarbeitung von zukünftigen Therapierichtlinien dienen.

Abstract

Background: Methotrexate (MTX) is one of the most frequently used disease-modifying anti-rheumatic drugs (DMARDs) for the treatment of rheumatic diseases. In clinical practice as well as in clinical trials, MTX is the gold standard for the treatment of rheumatoid arthritis. Nevertheless, a survey by the international 3e-initiative (Evidence, Experts, Exchange) among national and international experts identified 10 questions regarding the clinical use of MTX that had not yet been clarified. Therefore, it was the goal of this project to develop evidence-based recommendations on the use of MTX.

Materials and Methods: Between January and April 2007, experts from 17 countries agreed on 10 questions regarding the use of MTX. For answering these questions, “multinational fellows” performed a systematic literature research (SLR) up to October 2007. The SLR was completed according to the current recommendations of the Cochrane Collaboration and its results were presented to national groups of experts. Out of 17 000 articles retrieved by the SLR, only 304 articles were found to be applicable for answering the 10 questions. Based on these articles, recommendations were developed using a Delphi procedure.

Results: The 10 questions were divided into three topics: (A) therapeutic strategies, (B) treatment safety – monitoring and prevention and (C) treatment safety – complications. At the national meetings guided by the scientific committee, 68 German rheumatologists developed 10 recommendations in an interactive setting with a mean degree of acceptance of 90%.

Conclusion: The 3e-initiative has demonstrated that, despite long-standing experience with MTX, several issues with regard to its use in rheumatic diseases are currently unclear. The evidence-based recommendations on the use and monitoring of MTX as well as the management of therapeutic complications reported in this article represent the national consensus of experienced experts in the field and are of high importance for daily practice in rheumatology and for the development of future therapeutic recommendations.

Schlüsselwörter

Methotrexat - Dosierung - Überwachung - Folsäure - Schwangerschaft

Key words

methotrexate - dosing - monitoring - folic acid - pregnancy

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