title: Step-up combination versus switching of non-biological disease-modifying antirheumatic drugs in rheumatoid arthritis: results from a retrospective observational study.
abstract: BACKGROUND
  In rheumatoid arthritis (RA), treatment with disease-modifying antirheumatic drugs (DMARDs) frequently needs to be changed because of insufficient effectiveness.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Second Department of Medicine, Hietzing Hospital, Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Schoels
authors.forename: T
authors.initials: T
authors.lastname: Kapral
authors.forename: T
authors.initials: T
authors.lastname: Stamm
authors.forename: J S
authors.initials: JS
authors.lastname: Smolen
authors.forename: D
authors.initials: D
authors.lastname: Aletaha
mesh_terms: D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D001799:Blood Sedimentation / Q000187:drug effects; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007555:Isoxazoles / Q000009:adverse effects / Q000627:therapeutic use; D000077339:Leflunomide; D008297:Male; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012460:Sulfasalazine / Q000009:adverse effects / Q000627:therapeutic use; D017211:Treatment Failure
chemical_list: D018501:Antirheumatic Agents; D007555:Isoxazoles; D012460:Sulfasalazine; D000077339:Leflunomide; D008727:Methotrexate