LONG-TERM METHOTREXATE TREATMENT IN CORTICOSTEROID-DEPENDENT ASTHMA

Study Objective: To study the long-term efficacy and toxicity of low-dose methotrexate as corticosteroid-sparing adjunctive therapy in patients with corticosteroid-dependent bronchial asthma. Design: A prospectively evaluated case series. Patients: We studied 31 cushingoid asthmatics who needed daily prednisone and were found to be unable to reduce their prednisone dosage. These patients had used maximal daily doses of bronchodilator and inhaled corticosteroid and, on average, had used prednisone, 26.8 mg/d, for 4.7 years (range, 1 to 11 years). Of these 31 patients, 25 completed 18 to 28 months of methotrexate therapy. Intervention: Patients were treated for at least 18 months with low-dose methotrexate (range, 15 to 50 mg/wk). Results: The mean prednisone dose was reduced from 26.9 mg/d to 6.3 mg/d (P = 0.0001) in the 25 patients treated with long-term methotrexate: Fifteen patients discontinued the regular use of prednisone, 9 patients reduced prednisone use by more than 50%, and 1 patient failed to respond. The forced expiratory volume in 1 second (FEV1) improved from 1.7 L/s to 1.9 L/s (P = 0.0513), and subjective symptom scores for breathing ability, cough, wheeze, and frequency of nocturnal awakenings all improved. Adverse drug reactions were noted in 15 patients. These reactions were mild and did not lead to discontinuation of drug therapy. Conclusion: Methotrexate is effective and safe when used as a long-term, corticosteroid-sparing agent in patients with severe bronchial asthma.