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Influence of guideline adherence on outcome in a randomised controlled trial on the efficacy of methotrexate with folate supplementation in rheumatoid arthritis
  1. J Fransen1,
  2. R F J M Laan1,
  3. M A F J van der Laar2,
  4. T W J Huizinga3,
  5. P L C M van Riel1
  1. 1Department of Rheumatology, University Medical Centre Nijmegen, Nijmegen, Netherlands
  2. 2Department of Rheumatology, Medisch Spectrum Twente, Enschede, Netherlands
  3. 3Leiden University Medical Centre, Leiden, Netherlands
  1. Correspondence to:
    Dr J Fransen
    Department of Rheumatology, University Medical Centre Nijmegen, PO Box 9101, 6500 HB Nijmegen, Netherlands;


Objective: To study the influence of rheumatologists’ adherence to a methotrexate guideline on efficacy and toxicity in the treatment of rheumatoid arthritis.

Methods: In a 48 week randomised controlled trial of methotrexate, comparing folates with placebo, rheumatologists were advised on methotrexate dosage using a guideline reflecting daily practice. The influence of guideline non-adherence on outcome was analysed using generalised estimating equations and survival analysis.

Results: In 51% of the 411 study patients the guidelines were always followed. Non-adherence resulted in lower doses of methotrexate in 25% of cases, and higher doses in 24%. The reduction in the disease activity score was significantly greater (mean −0.4; p = 0.0085) in the adherent group than in the “low dose” group; the “high dose” group did not differ from the adherent group. Dropout caused by severe adverse events did not differ between the three groups.

Conclusions: There is an indication that adherence to guidelines on methotrexate dosage may benefit patients with rheumatoid arthritis by improving disease activity without increasing toxicity. For definite proof, a randomised controlled trial comparing guideline supported dosing with usual care is needed.

  • ACR, American College of Rheumatology
  • DAS, disease activity score
  • DMARD, disease modifying antirheumatic drug
  • EULAR, European League Against Rheumatism
  • RAI, Ritchie articular index
  • RCT, randomised controlled trial
  • TNFα, tumour necrosis factor α
  • VAS, visual analogue scale
  • rheumatoid arthritis
  • methotrexate
  • outcome

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