Although there was no significant difference between the methotrexate group and placebo group with regard to steroid-sparing ability, 3 of the 11 subjects demonstrated some response to methotrexate. No distinguishing features separated responders from nonresponders. The largest study to date suggested that the response to methotrexate occurs only after 12 weeks of study, since at this point in their study there was no significat reduction in steroid dosage in the methotrexate group compared with the placebo group, but at 24 weeks a significant difference existed. It is possible that by using a larger study population treated with methotrexate for a longer period, statistical significance might be achieved.
In comparison with other studies, we examined asthmatics who had more severe disease. Our patients required a mean of 28 mg/d of prednisone prior to enrollment in the study, and 30 mg/d to maintain optimum pulmonary function prior to commencing the study phases. This contrasts with many of the more recently published studies in which the dose of prednisone at enrollment was considerably lower: 13.1 mg and 14 mg. Although these studies demonstrated a significant reduction in the steroid dosage (30 and 50 percent, respectively), the reduction in the absolute response was small, eg, 3.5 mg. In addition, our mean patient population was younger than that of other published studies.
Since asthma is a chronic disease of predominantly younger patients, the likelihood is that therapy will be required long term. With this in mind; we were particularly careful in our assessment of possible drug toxicity. A physician blinded to the protocol monitored toxicity via a detailed questionnaire, weekly for the first 5 weeks and biweeldy thereafter. Although methotrexate-treated patients demonstrated slightly higher gastrointestinal side effects than placebo-treated patients, overall there was no difference in the two phases of the study. Notably, the prevalence of complaints, most commonly gastrointestinal, occurred predominantly in 4 of the 11 patients. This is likely due to the conventional antiasthma medications, eg, prednisone and theophylline. Significant hepatic toxic reactions were not detected. There was no evidence of pulmonary toxic reactions despite published reports that methotrexate pneumonitis occurs more commonly in patients with underlying pulmonary disease. canadian neightbor pharmacy
In summary, our study demonstrated important improvements in prednisone requirements in a group of relatively young patients with severe chronic steroid-dependent asthma, in both the methotrexate and placebo groups, but no significant differences between the groups. These results suggest that intensification of conventional medical therapy and frequent physician visits were more important than the addition of methotrexate. It is possible that a small subgroup of patients, who may have had more drug-responsive disease, was helped. Large multicentered studies are necessary to evaluate prospective identification of the subgroup of patients with severe steroid-dependent asthma who respond to low-dose methotrexate therapy.