RECOMMENDATION

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

K Visser¹, W Katchamart², E Loza³, J A Martinez-Lopez⁴, C Salliot⁵, J Trudeau⁶, C Bombardier^2,7, L Carmona⁴, D van der Heijde¹, J W J Bijlsma⁸, D T Boumpas⁹, H Canhao¹⁰, C J Edwards¹¹, V Hamuryudan¹², T K Kvien¹³, B F Leeb¹⁴, E M Martín-Mola¹⁵, H Mielants¹⁶, U Müller-Ladner¹⁷, G Murphy¹⁸, M Østergaard¹⁹, I A Pereira²⁰, C Ramos-Remus²¹, G Valentini²², J Zochling²³, M Dougados⁵

¹ Leiden University Medical Center, Leiden, The Netherlands
² Rheumatology Division, Department of Medicine, University of Toronto, Ontario, Canada
³ Department of Rheumatology, Hospital Clinico San Carlos, Madrid, Spain
⁴ Research Unit, Fundación Española de Reumatología, Madrid, Spain
⁵ Paris Descartes University, Medicine Faculty; UPRES-EA 4058; APHP, Rheumatology B Department, Cochin Hospital, Paris, France
⁶ CHUM-Hôpital Notre-Dame, Université de Montréal, Montréal, Canada
⁷ Division of Clinical Decision Making and Health Care Research, Health Network Research Institute, Toronto, Ontario, Canada
⁸ Department of Rheumatology and Clinical Immunology, University Medical Center, Utrecht, The Netherlands
⁹ Division of Rheumatology, University of Crete, Heraklion, Greece
¹⁰ Rheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa; Serviço de Reumatologia e Doenças Ósseas Metabólicas, Hospital de Santa Maria, Lisbon, Portugal
¹¹ Southampton University Hospital, Southampton, UK
¹² Istanbul University, Cerrahpasa Medical Faculty, Department of Internal Medicine, Division of Rheumatology, Istanbul, Turkey
¹³ Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway
¹⁴ State Hospital Stockerau, Center for Rheumatology, Lower Austria, Stockerau, Austria
¹⁵ Hospital Universitario La Paz, Department of Rheumatology, Universidad Autónoma, Madrid, Spain
¹⁶ Department of Rheumatology, University of Gent, Gent, Belgium
¹⁷ Department of Rheumatology and Clinical Immunology, Justus-Liebig-University Giessen, Kerckhoff Clinic, Bad Nauheim, Germany
¹⁸ Cork University Hospital, Wilton, Cork, Ireland
¹⁹ Departments of Rheumatology, Copenhagen University Hospitals at Hvidovre and Herlev, Denmark
²⁰ University Hospital of Santa Catarina, UFSC, Division of Rheumatology, Florianopolis, Brazil
²¹ Unidad de Investigación en Enf Cronico-Degenerativas, Guadalajara, Mexico
²² University of Naples, Department of Internal Medicine, Rheumatology Unit, Naples, Italy
²³ Menzies Research Institute, University of Tasmania, Hobart, Australia

Dr K Visser, Leiden University Medical Center, Department of Rheumatology, PO Box 9600, 2300 RC Leiden, The Netherlands; k.visser{at}lumc.nl

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.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

Relevant Article

Methotrexate: the gold standard without standardisation

Jonathan Kay and Rene Westhovens
Ann Rheum Dis 2009 68: 1081-1082. [Extract] [Full Text] [PDF]

This article has been cited by other articles:

• Kay, J., Westhovens, R. (2009). Methotrexate: the gold standard without standardisation. Ann Rheum Dis 68: 1081-1082 [Full Text]  
• Visser, K, van der Heijde, D (2009). Optimal dosage and route of administration of methotrexate in rheumatoid arthritis: a systematic review of the literature. Ann Rheum Dis 68: 1094-1099 [Abstract] [Full Text]  
• Katchamart, W, Trudeau, J, Phumethum, V, Bombardier, C (2009). Efficacy and toxicity of methotrexate (MTX) monotherapy versus MTX combination therapy with non-biological disease-modifying antirheumatic drugs in rheumatoid arthritis: a systematic review and meta-analysis. Ann Rheum Dis 68: 1105-1112 [Abstract] [Full Text]  
• Salliot, C, van der Heijde, D (2009). Long-term safety of methotrexate monotherapy in patients with rheumatoid arthritis: a systematic literature research. Ann Rheum Dis 68: 1100-1104 [Abstract] [Full Text]