title: Methotrexate in combination with sulfasalazine is more effective in rheumatoid arthritis patients who failed sulfasalazine than in patients naive to both drugs.
abstract: OBJECTIVE
  For pharmacological reasons, the effect of the combination of MTX and SSZ may be different in RA patients who are naïve to these drugs compared to patients with an insufficient response to one of them. Therefore, we compared the results of randomized controlled trials (RCTs) on the combination of MTX and SSZ in naïve patients and in patients with an insufficient response to SSZ.
  
  
  METHODS
  A systematic literature search was performed to identify RCTs that compared the MTX-SSZ combination to either drug alone. The databases MEDLINE and the Cochrane Clinical Trials registry were searched from 1966 up to April 2007. The efficacy of the single therapeutic agents or their combination was assessed using the mean change in the disease activity score (DAS) and the ACR improvement criteria.
  
  
  RESULTS
  Four RCTs were identified to compare the efficacy of the combination MTX-SSZ to the efficacy of either drug alone. Two parallel trials were performed with patients naïve to both drugs and two add-on trials were performed in SSZ failures. In the trials with naïve patients, the mean DAS changes for the combination MTX and SSZ pointed to a sub-additive efficacy. In the trials with patients who previously failed to SSZ, the mean DAS changes for the combination MTX and SSZ indicated additive efficacy.
  
  
  CONCLUSIONS
  In RA, addition of MTX to SSZ is a therapeutic option in SSZ failures, whereas combination of MTX and SSZ in DMARD-naïve patients has no added value.
authors.affiliation: Department of Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. LSchipper@reuma.umcn.nl
authors.forename: Lydia G
authors.initials: LG
authors.lastname: Schipper
authors.forename: Jaap
authors.initials: J
authors.lastname: Fransen
authors.forename: Pilar
authors.initials: P
authors.lastname: Barrera
authors.forename: Piet L C M
authors.initials: PL
authors.lastname: Van Riel
mesh_terms: D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D012460:Sulfasalazine / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D012460:Sulfasalazine; D008727:Methotrexate