Combination of methotrexate and sulphasalazine vs methotrexate alone: a randomized open clinical trial in rheumatoid arthritis patients resistant to sulphasalazine therapy.

To compare efficacy, toxicity, and the pharmacokinetics of the combination of sulphasalazine (SASP) and methotrexate (MTX) vs MTX alone in the treatment of SASP-resistant RA we conducted a controlled open clinical trial. Forty RA patients with active arthritis despite adequate SASP therapy, were allocated randomly to regimes of either SASP+MTX or MTX alone. The patients were evaluated openly by a single observer for 24 weeks. In the first 15 patients using the combination, pharmacokinetics of MTX without and with SASP were studied. Thirty-eight patients completed the trial. The mean decrease in the disease activity score in the group of patients receiving the combination was significantly greater than in the MTX group (-2.6 vs -1.3 respectively). The same pattern was seen concerning the other efficacy variables. There was no difference in the occurrence of toxicity. SASP had no influence on the pharmacokinetics of MTX. In conclusion in this open study the efficacy of the combination of MTX and SASP seems to be superior to MTX alone, the toxicity of both therapies was similar. This effect was not explained by the pharmacokinetics of MTX which were not altered by concomitant SASP administration.