COMPARISON OF ORAL PULSE METHOTREXATE WITH PLACEBO IN THE TREATMENT OF SEVERE GLUCOCORTICOSTEROID-DEPENDENT ASTHMA

Background: This study compared the efficacy of weekly oral administra tion of methotrexate and placebo in treatment of 24 subjects with chro nic glucocorticosteroid-dependent asthma. Methods: The 33-week randomi zed, double-blind, placebo-controlled crossover trial compared once we ekly 15 mg doses of methotrexate with placebo. At the time of entry th e subjects' mean dosage of prednisone was 23.8 mg/day (range, 12.5 to 85 mg) and glucocorticosteroid therapy had been used continuously for a mean duration of 78 months (range, 5 to 360 months). Results: Of the 21 subjects who completed the study, 13 tolerated lower daily prednis one doses during methotrexate treatment compared with placebo. When tr eated with methotrexate, subjects required 14.2% less prednisone than when treated with placebo (p = 0.0447), their subjective symptom score s improved 21.4% (p < 0.05), and mean forced expiratory volume in 1 se cond values tended to improve. Mean serum theophylline levels did not change significantly between the methotrexate and placebo arms of the study. Adverse effects were minimal, with nausea and headache occurrin g twice as often during methotrexate therapy compared with placebo. Co nclusion: Short-term, low-dose, pulse therapy with orally administered methotrexate results in a decrease in the daily glucocorticosteroid r equirement in a majority of subjects with severe asthma and is accompa nied by improvement in subjective symptom scores without unacceptable side effects or deterioration of pulmonary function.