Article Text

Download PDFPDF
Extended report
Current evidence for the management of rheumatoid arthritis with synthetic disease-modifying antirheumatic drugs: a systematic literature review informing the EULAR recommendations for the management of rheumatoid arthritis
  1. Cécile Gaujoux-Viala1,2,
  2. Josef S Smolen3,
  3. Robert Landewé4,
  4. Maxime Dougados2,
  5. Tore K Kvien5,
  6. Emilio Martin Mola6,
  7. Marieke Scholte-Voshaar7,
  8. Piet van Riel8,
  9. Laure Gossec2
  1. 1Pierre et Marie Curie University-Paris VI, APHP, Rheumatology, Pitié-Salpétrière Hospital, Paris, France
  2. 2Paris Descartes University, Medicine Faculty; UPRES-EA 4058; APHP, Rheumatology B Department, Cochin Hospital, Paris, France
  3. 3Department of Rheumatology, Medical University of Vienna and Hietzing Hospital, Vienna, Austria
  4. 4Department of Internal Medicine/Rheumatology, University Hospital Maastricht, Maastricht, The Netherlands
  5. 5Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway
  6. 6Department of Rheumatology, Hospital Universitario La Paz, Madrid, Spain
  7. 7Department of Rheumatology, VU University Medical Center and Jan van Breemen Institute, Amsterdam, The Netherlands
  8. 8Department of Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
  1. Correspondence to Dr Cécile Gaujoux-Viala, Hôpital Pitié-Salpétrière, Service de Rhumatologie, 83 Boulevard de l’Hôpital, 75651 Paris Cedex 13, France; cecilegaujouxviala{at}


Objectives To assess the efficacy and safety of synthetic disease-modifying antirheumatic drugs (DMARDs) in adults with rheumatoid arthritis (RA)—a first step in a European League Against Rheumatism (EULAR) initiative to produce recommendations for the management of RA.

Methods A systematic review of the literature using PubMed, Embase and the Cochrane library was performed up to January 2009. All randomised controlled trials (RCTs) reporting the efficacy of synthetic DMARDs (vs placebo or other synthetic DMARDs) on signs and symptoms, disability and/or radiographic structural damage in patients with RA were selected. Studies of biological agents or glucocorticoids were excluded. A pooled effect size (ES) was calculated by meta-analysis. Safety and the occurrence of infections and neoplasia was also assessed.

Results 97 RCTs (14 159 patients) were analysed for efficacy. The pooled analysis indicated that methotrexate (MTX) was more efficacious in reducing signs and symptoms, disability and radiographic structural damage than other synthetic DMARDs pooled: ES for swollen joint count (SJC) versus pooled DMARDs=1.42 (95% CI 0.65 to 2.18). Leflunomide appeared to be as effective as MTX. Sulfasalazine and injectable gold were efficacious in reducing signs and symptoms and structural damage. Ciclosporin, minocycline, tacrolimus and hydroxychloroquine showed some efficacy in reducing SJC. Auranofin and D-penicillamine showed no significant superiority over placebo. The risks of cancer and of infection were increased with cyclophosphamide and azathioprine.

Conclusions MTX was well-tolerated and effective in reducing signs and symptoms, disability and structural damage. A comparison with other synthetic DMARDs was in favour of MTX, though at the tested doses MTX and leflunomide were equally effective.

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • Competing interests None. Francis Berenbaum was the handling editor.

  • Provenance and peer review Not commissioned; externally peer reviewed.