Background: Though several drugs have been tested, the choice of the ideal steroid-sparing agent in steroid-dependent asthmatic patients remains unclear. Our objective was to evaluate the efficacy and tolerance of methotrexate in low weekly doses in order to decrease chronic oral steroid requirements in asthmatic patients.
Design: double blind randomized placebo-controlled study.
Setting: The study was performed in a 760-bed teaching hospital.
Patients: 46 steroid-dependent asthmatic patients were randomized.
Interventions: PATIENTS received 10mg of methotrexate or placebo once weekly for a year. The 6-methylprednisolone was progressively tapered (2mg/day every two weeks) until FEV1 diminished by 5% or more; 6-methylprednisolone was then increased until the previous FEV1 was reached, and the procedure was repeated throughout follow-up.
Measurements: Blood and urine analyses and bone densitometry were performed at entry and at the end of the study. Pulmonary function was tested monthly during the first three months and then every three months until the end.
Results: Thirty-nine patients were evaluated at interim analysis. A 54.8% decrease (9.5+/-4.9 mg/day) in 6-methylprednisolone dose was observed in the methotrexate group and a 4.4% decrease (0.5+/-7.2 mg/day) in the placebo group (P<0.001). There was no significant decrease of FEV1 in either group. No changes in bone metabolism were observed except for a non-statistically significant increase in osteocalcin levels in the treated group compared to a decrease in the placebo group. Toxicity was mild.
Conclusions: (1) Methotrexate is an effective steroid-sparing agent. (2) A dosage lower than the one recommended in the literature is effective. (3) Tolerance is good. (4) No benefit or detrimental effects in bone metabolism were observed after one year.