Multinational evidence-based recommendations for the use of methotrexate in rheumatic disorders with a focus on rheumatoid arthritis: integrating systematic literature research and expert opinion of a broad international panel of rheumatologists in the 3E Initiative

Abstract

Objectives:To develop evidence-based recommendations for the use of methotrexate in daily clinical practice in rheumatic disorders.Methods:751 rheumatologists from 17 countries participated in the 3E (Evidence, Expertise, Exchange) Initiative of 2007–8 consisting of three separate rounds of discussions and Delphi votes. Ten clinical questions concerning the use of methotrexate in rheumatic disorders were formulated. A systematic literature search in Medline, Embase, Cochrane Library and 2005–7 American College of Rheumatology/European League Against Rheumatism 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 16 979 references was identified, of which 304 articles were included in the systematic reviews. Ten multinational key recommendations on the use of methotrexate were formulated. Nine recommendations were specific for rheumatoid arthritis (RA), including the work-up before initiating methotrexate, optimal dosage and route, use of folic acid, monitoring, management of hepatotoxicity, long-term safety, mono versus combination therapy and management in the perioperative period and before/during pregnancy. One recommendation concerned methotrexate as a steroid-sparing agent in other rheumatic diseases.Conclusions:Ten recommendations for the use of methotrexate 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.

Role of Methotrexate Intolerance Severity Score (Miss) in Rheumatoid Arthritis to Know Methotrexate Intolerance: A 2-Year Prospective Study.

“…Keeping the usefulness of MTX and mitigation by various procedures in view use of MISS is recommended to apply for patients of RA on MTX. The mitigation procedures include change of route of MTX administration, folic acid administration, antiemetic and behavioral therapy (Tables 7-14) [11,12].…”

Effects of Concomitant Methotrexate on Large Joint Replacement in Patients With Rheumatoid Arthritis Treated With Tumor Necrosis Factor Inhibitors: A Multicenter Retrospective Cohort Study in Japan

“…This was subsequently increased to 16 mg/week for patients with RA in February 2011. A systematic literature review of MTX monotherapy revealed recommendations to start oral MTX at 10-15 mg/week, with escalation up to 20-30 mg/week depending on clinical response and tolerability (29). However, little is known about the minimally effective dose of MTX when used in combination with a TNF inhibitor in patients with RA.…”

Cost‐Effectiveness Model for Evaluating New Diagnostic Tests in the Evaluation of Patients With Inflammatory Arthritis at Risk of Having Rheumatoid Arthritis

“…MTX is the cornerstone of treatment in RA (18,19). On average, 50-70% of patients respond well to this drug (24,25). We modeled treatment in the first 12 months by starting MTX in patients who scored 6 or more points as suggested by the ACR/EULAR 2010 RA criteria, and by employing a wait-and-see policy for the patients scoring less than 6 points.…”