TREATMENT OF RHEUMATOID-ARTHRITIS WITH METHOTREXATE ALONE, SULFASALAZINE AND HYDROXYCHLOROQUINE, OR A COMBINATION OF ALL 3 MEDICATIONS

mon disease that causes substantial morbidity and mortality. The respo nses of patients with rheumatoid arthritis to treatment with a single so-called disease-modifying drug, such as methotrexate, are often subo ptimal. Despite limited data, many patients are treated with combinati ons of these drugs. Methods. We enrolled 102 patients with rheumatoid arthritis and poor responses to at least one disease-modifying drug in a two-year, double-blind, randomized study of treatment with methotre xate alone (7.5 to 17.5 mg per week), the combination of sulfasalazine (500 mg twice daily) and hydroxychloroquine (200 mg twice dally), or all three drugs. The dose of methotrexate was adjusted in an attempt t o achieve remission in all patients. The primary end point of the stud y was the successful completion of two years of treatment with 50 perc ent improvement in composite symptoms of arthritis and no evidence of drug toxicity.Results. Fifty of the 102 patients had 50 percent improv ement at nine months and maintained at least that degree of improvemen t for two years without evidence of major drug toxicity. Among them we re 24 of 31 patients treated with all three drugs (77 percent), 12 of 36 patients treated with methotrexate alone (33 percent, P<0.001 for t he comparison with the three-drug group), and 14 of 35 patients treate d with sulfasalazine and hydroxychloroquine (40 percent, P=0.003 for t he comparison with the three-drug group). Seven patients in the methot rexate group and three patients in each of the other two groups discon tinued treatment because of drug toxicity. Conclusions. In patients wi th rheumatoid arthritis, combination therapy with methotrexate, sulfas alazine, and hydroxychloroquine is more effective than either methotre xate alone or a combination of sulfasalazine and hydroxychloroquine.