Benefits of low weekly doses of methotrexate in steroid-dependent asthmatic patients. A double-blind, randomized, placebo-controlled study.
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.


METHODS



METHODS
double blind randomized placebo-controlled study.


METHODS
The study was performed in a 760-bed teaching hospital.


METHODS
46 steroid-dependent asthmatic patients were randomized.


METHODS
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.


METHODS
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.
Comet
Ricard
R
Pulmonary Service, Hospital de Sabadell (Corporació Parc Taulí), Parc Taulí s/n, 08208 Sabadell, Barcelona, Spain.
Domingo
Christian
C
Larrosa
Marta
M
Morón
Anisi
A
Rué
Montserrat
M
Amengual
Maria-Jose
MJ
Marín
Albert
A
D000328:Adult; D000368:Aged; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001842:Bone and Bones / Q000187:drug effects; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D008775:Methylprednisolone / Q000008:administration & dosage; D008875:Middle Aged; D012129:Respiratory Function Tests; D013256:Steroids / Q000008:administration & dosage
D001993:Bronchodilator Agents; D005938:Glucocorticoids; D013256:Steroids; D008775:Methylprednisolone; D008727:Methotrexate