Objectives: To develop evidence-based recommendations for the use of methotrexate (MTX) in daily clinical practice in rheumatic disorders.
Methods: A total of 751 rheumatologists from 17 countries participated in the 3E (Evidence Expertise Exchange) Initiative of 2007-2008 consisting of 3 separate rounds of discussions and Delphi votes. Ten clinical questions concerning the use of MTX in rheumatic disorders were formulated. A systematic literature search in Medline, Embase, Cochrane Library and 2005-2007 ACR/EULAR meeting abstracts was conducted. Selected articles were systematically reviewed and the evidence was appraised according to the Oxford Levels of Evidence. Each country elaborated a set of national recommendations. Finally, multinational recommendations were formulated and agreement among the participants and the potential impact on their clinical practice was assessed.
Results: A total of 16979 references were identified, of which 304 articles were included in the systematic reviews. Ten multinational key recommendations on the use of MTX were formulated. Nine recommendations were specific for rheumatoid arthritis, including the work-up before initiating MTX, optimal dosage and route, use of folic acid, monitoring, management of hepatotoxicity, long-term safety, mono versus combination therapy and management in the peri-operative period and before/during pregnancy. One recommendation concerned MTX as a steroid-sparing agent in other rheumatic diseases.
Conclusions: Ten recommendations for the use of MTX in daily clinical practice focussed on RA were developed, which are evidence-based and supported by a large panel of rheumatologists, enhancing their validity and practical use.