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Rheumatology (Oxford). 2009 Jul;48(7):828-33. doi: 10.1093/rheumatology/kep090. Epub 2009 May 20.

Methotrexate in combination with sulfasalazine is more effective in rheumatoid arthritis patients who failed sulfasalazine than in patients naive to both drugs.

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  • 1Department of Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.



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.


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.


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.


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.

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