Twelve years' experience with methotrexate for GINA treatment step 5 asthma patients.

BACKGROUND: Certain studies have shown the beneficial effects of methotrexate (MTX) in asthma patients. Here we describe the drug's tolerance and oral corticosteroid sparing capacity in a long-term observational study.
METHODS: Forty-four patients with steroid-dependent asthma treated with 10 mg per week of oral MTX were prospectively followed for 91.3 +/- 39.5 months. INTERVENTION: blood analysis each 3 months; spirometry monthly during the first 3 months and then every 3-6 months; liver ultrasound when an accumulated dose of 1500 mg was reached or whenever hepatic function was altered.
RESULTS: Two patients who dropped out early were excluded. Mean accumulated dose of MTX was 3.499 +/- 2.207 mg. Corticosteroid use was reduced from 15.1 +/- 8.2 to 2.64 +/- 5.35 mg (p < 0.008) and was withdrawn in 25 patients. In the remaining 17 patients, the dose was reduced from 17.1 +/- 9.1 mg to 6.5 +/- 6.8 mg. FEV(1) (% predicted) was 66.2 +/- 19.7 at the beginning and 65.7 +/- 19.1 at the end. Haematology was normal and only a mild increase in hepatic enzymes was observed in four patients, which normalized after treatment discontinuation. Hair loss was observed in one case.
CONCLUSIONS: In our series, a substantial, safe decrease in oral corticosteroid requirements was observed, probably due, to some extent, to MTX therapy. Oral corticosteroids were withdrawn completely in 59% of patients. Liver function was impaired in some patients; however, it recovered after MTX withdrawal and MTX could be safely reintroduced. The association of oral corticosteroids and MTX did not increase the number of side-effects and immunity was not affected. We were unable to identify a factor that could predict which patients would benefit most from MTX treatment. Some limitations of the study include the lack of control of asthma exacerbations and the lack of booster courses of corticosteroids.