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Rheumatology Advance Access originally published online on May 20, 2009
Rheumatology 2009 48(7):828-833; doi:10.1093/rheumatology/kep090
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© The Author 2009. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

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

Lydia G. Schipper1, Jaap Fransen1, Pilar Barrera1 and Piet L. C. M. Van Riel1

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

Correspondence to: Lydia G. Schipper, Department of Rheumatology, Radboud University Nijmegen Medical Centre, PO Box 9101, NL-6500 HB Nijmegen, The Netherlands. E-mail: LSchipper{at}reuma.umcn.nl


  Abstract

Objectives. 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.

KEY WORDS: Rheumatoid arthritis, Combination drug therapy, Methotrexate, Sulfasalazine, Therapeutic use

Submitted 2 October 2008; revised version accepted 20 March 2009.
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