Clinical Rheumatology

, Volume 29, Issue 6, pp 629–635 | Cite as

Methotrexate treatment in rheumatoid arthritis: management in clinical remission, common infection and tuberculosis. Results from a systematic literature review

  • Mónica Bogas
  • Pedro Machado
  • Ana Filipa Mourão
  • Lúcia Costa
  • Maria José Santos
  • João Eurico Fonseca
  • José António P. Silva
  • Helena CanhãoEmail author
Original Article


This work was performed as part of the Portuguese participation in the 3E Initiative 2007–2008, dedicated to the use of methotrexate (MTX) in rheumatic conditions. Three questions raised by Portuguese rheumatologists and considered relevant to clinical practice remained out of the selection of a set of ten key questions formulated to further establish multinational recommendations on the use of MTX in rheumatic diseases. The authors collected and analyzed all the evidence available by using a systematic literature search methodology and selection criteria concerning the following issues in rheumatoid arthritis (RA): (1) the management of MTX after clinical remission; (2) the management of MTX during infections and (3) the screening and treatment of tuberculosis in patients on MTX treatment. A total of 1,862 references were identified, of which 163 were selected for detailed analysis and 12 included in the final review. The evidence was appraised according to the Oxford Centre for Evidence-based Medicine (EBM) levels of evidence. Although with limited evidence, the authors concluded that: (1) extending the interval for MTX therapy may be a valid alternative regimen in a subset of RA patients in clinical remission (EBM level 2b); (2) MTX may be safe during some common infections in RA patients (EBM level 3b/4); (3) screening and treatment of TB in patients on MTX should be similar to the general population (EBM level 4). The evidence available to support clinical decisions in this area is very limited in number and quality. There is a need for further research and while that is unavailable, practical decisions have to rely on experience and expert opinion.


Infection Methotrexate Remission Rheumatoid arthritis Systematic literature review Tuberculosis 



We wish to thank the librarian, Helena Donato, and the epidemiologists, Paulo Nicola and Nuno Lunet, for their collaboration and support in the search and in the methodology used. We also thank Prof Maxime Dougados and the members of the 3E Initiative International Scientific Committees for their encouragement and guidance.


This work has been supported by an unrestricted grant from Abbott Immunology. Abbott had no role in the study design, literature search, data collection, analysis, and writing of this report.

Conflicts of interest



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Copyright information

© Clinical Rheumatology 2010

Authors and Affiliations

  • Mónica Bogas
    • 1
  • Pedro Machado
    • 2
  • Ana Filipa Mourão
    • 3
  • Lúcia Costa
    • 1
  • Maria José Santos
    • 4
  • João Eurico Fonseca
    • 5
    • 6
  • José António P. Silva
    • 2
  • Helena Canhão
    • 5
    • 6
    Email author
  1. 1.Division of RheumatologyUnidade Local de Saúde do Alto MinhoPonte de LimaPortugal
  2. 2.Rheumatology DepartmentHospital da Universidade de CoimbraCoimbraPortugal
  3. 3.Rheumatology Department, Centro Hospitalar de Lisboa OcidentalEgas Moniz HospitalLisbonPortugal
  4. 4.Rheumatology DepartmentHospital Garcia da OrtaAlmadaPortugal
  5. 5.Rheumatology DepartmentHospital Santa MariaLisbonPortugal
  6. 6.Rheumatology Research Unit, Instituto de Medicina MolecularFaculdade de Medicina de Lisboa, Universidade de LisboaLisbonPortugal

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