To overcome the possible carryover effect of methotrexate, the last 4 weeks of each treatment period were used for analysis of steroid requirement and pulmonary function. These variables were compared with the last 2 weeks of the initialization phase using analysis of variance. The paired t test was used to compare parametric data, including prednisone dose and pulmonary functions (FEVj and FVC) between the methotrexate group and the placebo group. On completion of the study, patients were subdivided into those who received methotrexate first (A) and those who received placebo first (B). Comparisons of parametric data of steroid dose and pulmonary functions were made with each subgroup, using the paired t test and the Student’s t test when appropriate. Toxicity data were compared between each treatment group using the McNemer’s x2 test on each individual symptom. mycanadianpharmacy
A total of 14 patients were enrolled in the study. Three of these subsequently were removed from the study; one patient whose condition was too unstable during the initialization phase because of uncontrolled asthma, withdrew himself from the study, the second patient was not steroid-dependent, and the third patient developed significant alopecia during the study. The characteristics of the study population assessed during the initialization phase are shown in Table 1. Notably, the study group consisted of severely steroid-dependent asthmatics, requiring a mean prednisone dose of greater than 30 mg/d to optimize their pulmonary function. All patients were receiving maintenance asthma medications, including theophylline, an inhaled p-agonist, and high-dose inhaled steroids. Four patients were treated with anticholinergic agents, and five were treated with cromolyn sodium. Six patients were randomized to the methotrexate treatment group first and five were randomized to the placebo treatment group first.
The design of the study was to optimize the patient’s symptoms and pulmonary function during the initialization period, and thereafter maintain this level of function throughout the study period while adjusting steroids to the minimum dose needed to maintain function. During both study phases, with the addition of methotrexate and placebo on a background of conventional antiasthma medications, the pulmonologist attempted to maintain stable pulmonary function by increasing or decreasing the prednisone dose. The mean FEVv FVC, and FEV/FVC ratio during the two investigative phases of the study are displayed in Table 2. As expected, there was no significant change in pulmonary function over the duration of the study.
Table 1—Characteristics of 11 Patients Who Completed the Study at the Start of Enrollment and During the Initialization Phase
|Sex/Age,yr||, Prednisone, mg/d||FEVj/FVC, L/min|
Table 2—Comparison of Clinical Data During the Initialization, Placebo, and Methotrexate Phases in the 11 Patients Who Completed the Study
|FVC, L||3.8 ±0.4||3.8±0.4||3.9±0.5|
|FEVj/FVC||61.2±3.5||62.7 ±3.1||64 ±3.5|
|PFM, L/min||310 ±37||319 ±38||308 ±37*|
|Symptom score,||2.01 ±0.018||2.03 ±0.18||1.89 ±0.18*|
|Prednisone,mg/d||30.78 ±4.9||24.5 ±3.9$||20.1±3.8ф|