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Limited efficacy of conventional DMARDs after initial methotrexate failure in patients with recent onset rheumatoid arthritis treated according to the disease activity score
  1. Sjoerd M van der Kooij1,
  2. Jeska K de Vries-Bouwstra2,
  3. Yvonne P M Goekoop-Ruiterman1,
  4. Derkjen van Zeben3,
  5. Pit J S M Kerstens4,
  6. Andreas H Gerards5,
  7. Johannes H L M van Groenendael6,
  8. Johanna M W Hazes7,
  9. Ferdinand C Breedveld1,
  10. Cornelia F Allaart1,
  11. Ben A C Dijkmans8
  1. 1
    Leiden University Medical Center, Leiden, Netherlands
  2. 2
    VU Medical Center, Amsterdam, Netherlands
  3. 3
    Sint Franciscus Gasthuis, Rotterdam, Netherlands
  4. 4
    Jan van Breemen Institute, Amsterdam, Netherlands
  5. 5
    Vlietland Hospital, Schiedam, Netherlands
  6. 6
    Franciscus Hospital, Roosendaal, Netherlands
  7. 7
    Erasmus Medical Center, Rotterdam, Netherlands
  8. 8
    VU Medical Center, and Jan van Breemen Institute, Amsterdam, Netherlands
  1. Sjoerd M Van der Kooij, Department of Rheumatology C-01-R, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, Netherlands; smvanderkooij{at}


Objectives: To determine the efficacy of subsequent disease modifying antirheumatic drug (DMARD) therapies after initial methotrexate (MTX) failure in patients with recent onset rheumatoid arthritis (RA), treated according to the DAS for 2 years.

Methods: In groups 1 and 2 of the BeSt study, 244 RA patients were initially treated with MTX 15–25 mg/week. Patients who discontinued MTX because of insufficient clinical response (disease activity score, DAS >2.4) or toxicity were classified as “MTX failures.” In group 1, these patients switched to sulfasalazine (SSA), then leflunomide and finally to MTX + infliximab (IFX). In group 2, “MTX failures” added SSA to MTX, then hydroxychloroquine (HCQ), then prednisone, and eventually switched to MTX + IFX. “MTX successes” were patients who achieved a DAS ⩽2.4 after 2 years while still on MTX monotherapy. Total Sharp/van der Heijde score (TSS) progression from 0–2 years was assessed in “MTX failures” versus “MTX successes.”

Results: After 2 years, 162/244 patients (66%) had discontinued MTX because of insufficient response or toxicity. Of these, 78% also failed on SSA (adding or switching), 87% subsequently failed on leflunomide (in group 1), and 64% on MTX + SSA + HCQ (in group 2). 34 of 48 patients (71%) in groups 1 and 2 were successfully treated with MTX + IFX. After 2 years, regardless of the “success” on subsequent DMARDs, “ MTX failures” had a median TSS progression of 3 units (mean 9) versus 1 unit (mean 3) in “MTX successes” (p = 0.007).

Conclusion: After failure on initial MTX, treatment with subsequent conventional DMARDs is unlikely to result in a DAS ⩽2.4 and allows progression of joint damage.

  • rheumatoid arthritis
  • methotrexate
  • DMARDs
  • joint damage

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  • Competing interests: Professor Dr FC Breedveld did a paid expert testimony for Centocor in 1996 and was a paid speaker in a Schering Plough sponsored symposia. Dr CF Allaart was a paid speaker in a Schering Plough sponsored symposium in 2006.

  • Funding: The BeSt study was supported by a grant of the Dutch College for Health Insurance Companies (CVZ). Schering-Plough and Centocor provided additional funding. The funding sources were not involved in the design of the study, the collection, analysis and interpretation of data, the writing of the report or the decision to submit the paper for publication.

  • All authors: FARR Trial Group, Leiden, Netherlands

  • Abbreviations:
    adverse drug events
    disease activity score
    disease modifying antirheumatic drugs
    erythrocyte sedimentation rate
    European League Against Rheumatism
    health assessment questionnaire
    interquartile range
    non-steroidal anti-inflammatory drugs
    rheumatoid arthritis
    Ritchie articular index
    smallest detectable change
    swollen joint count
    total Sharp/van der Heijde score
    visual analogue scale