To compare efficacy and tolerability of combined therapy with methotrexate (MTX), sulfasalazine (SSZ) and hydroxychloroquine (HCQ) with MTX-monotherapy in patients with rheumatoid arthritis (RA).
RA patients (n = 60) who had not been treated with the above drugs were randomized (1:1) to receive either the triple drug combination or MTX alone in a 2-year open study. SSZ was given in a dose of 2.0 g/day, HCQ--200 mg/day. A MTX dose was gradually increased from 7.5 mg/week to 17.5 mg/week in an attempt to achieve remission in all the patients. Basic criterion of the treatment efficacy was achievement of a significant clinical effect (> 50% response according to the American College of Rheumatology--ACR criteria) in stability of the positive effect beginning from the ninth month of the study up to its end with no evidence of serious drug toxicity.
13 of 18 patients treated with the triple therapy (72.2%) and 6 of 20 patients treated with MTX alone (30.0%; p = 0.013) achieved an ACR > 50% response by the end of 18 months of therapy. 11 of 18 patients (61.1%) from the combined therapy group and 5 of 20 patients (25%; p = 0.024) from MTX monotherapy group maintained ACR > 50% response from month 9 to 18 of the study without any evidence of major drug toxicity. Two patients (11.1%) in the combined therapy group and 4 patients (20%) in the MTX group discontinued the treatment because of drug toxicity.
In patients with RA the triple combination therapy with MTX, SSZ and HCQ given during 1.5 year is more effective than MTX alone. The triple combination of MTX, SSZ and HCQ is well tolerated.