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Step-up combination versus switching of non-biological disease-modifying antirheumatic drugs in rheumatoid arthritis: results from a retrospective observational study
  1. M Schoels1,
  2. T Kapral2,
  3. T Stamm2,
  4. J S Smolen1,
  5. D Aletaha2
  1. 1Second Department of Medicine, Hietzing Hospital, Vienna, Austria
  2. 2Department of Rheumatology, Internal Medicine III, Medical University of Vienna, Vienna, Austria
  1. Correspondence to:
    Dr D Aletaha
    Department of Rheumatology, Medical University of Vienna, Vienna 1090, Austria; daniel.aletaha{at}


Background: In rheumatoid arthritis (RA), treatment with disease-modifying antirheumatic drugs (DMARDs) frequently needs to be changed because of insufficient effectiveness.

Aim: To compare the clinical outcomes of two potential strategies for patients experiencing DMARD discontinuations related to ineffectiveness: switching to another DMARD or step-up combination therapy of the present DMARD with a new one.

Methods: In a large observational database of 4585 DMARD courses in 1214 patients with RA, all patients who had experienced a change in treatment regimen were identified, and retention, effectiveness and safety of these subsequent treatment courses between the two strategies (switching vs step-up combination). All analyses were stratified according to the type of the new DMARD into methotrexate (MTX), sulphasalazine (SSZ) or leflunomide (LEF); all other DMARDs were excluded.

Results: Kaplan–Meier analysis for MTX courses showed no significant difference in overall retention rates between the strategies of adding MTX and switching to MTX (p = 0.49 by log rank test). Likewise, switching or adding did not result in significantly different retention rates for SSZ and LEF (p = 0.61 and 0.74, respectively). This similarity between strategies remained after adjusting for several confounding variables. The frequencies of treatment terminations related to ineffectiveness or toxicity were likewise similar between the two strategies for the MTX, SSZ and LEF groups. This was also confirmed by the similarity of erythrocyte sedimentation rates that were reached at the end of the two therapeutic strategies for all three drugs, in adjusted analysis.

Conclusion: Given all limitations of observational studies, the present data indicate that in situations of ineffective DMARD treatments, step-up combination therapy using traditional DMARDs, such as MTX, SSZ or LEF, bears no clear clinical advantage over switching to the new DMARD. Our results do not implicate any predication about step-up design including biologicals, where the benefit of combination therapy has been suggested convincingly.

  • DMARD, disease-modifying antirheumatic drug
  • ESR, erythrocyte sedimentation rate
  • LEF, leflunomide
  • MTX, methotrexate
  • RA, rheumatoid arthritis
  • SSZ, sulphasalazine

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  • Published Online First 23 February 2007

  • Competing interests: None declared.