Inhaled corticosteroids, such as beclomethasone, are the medications most commonly used to control asthma, but problems with compliance limit their effectiveness, especially in children and elderly patients. Leukotriene receptor antagonists are now considered to be alternative first-line controller medications. The oral leukotriene receptor antagonist montelukast has demonstrated efficacy in both adults and children, and is well tolerated. Malmstrom and associates compared oral montelukast, inhaled beclomethasone and placebo in patients with chronic asthma who required the daily use of a controller medication.
The 12-week study included 895 patients 15 to 85 years of age who required at least a single daily puff of an as-needed, short-acting inhaled beta agonist. Eligibility criteria also included a forced expiratory volume in one second (FEV1) of 50 to 85 percent of the predicted value, and an increase of at least 15 percent in the absolute FEV1 after inhalation of a beta agonist.
Patients were randomized to receive one of three treatments: (1) montelukast, 10 mg in the evening, (2) inhaled beclomethasone, 200 μg twice daily or (3) placebo. The study design included a two-week placebo run-in period, a 12-week double-blind treatment period and a three-week double-blind placebo washout period. Withdrawal from therapy was evaluated by switching a subset of patients who received active treatment to placebo in a blinded manner. If severe episodes of asthma developed, patients were treated with oral steroids; patients who had more than two worsening episodes were dropped from the study.
Spirometry was performed at each visit, and participants completed questionnaires about daytime asthma symptoms and nocturnal awakening. They also kept a diary of morning and evening peak expiratory flow rates and daily use of as-needed salbutamol.
Compared with placebo, both montelukast and beclomethasone provided significant benefit with respect to FEV1, daytime symptom scores, as-needed beta agonist use, morning and evening peak expiratory flow rates and nocturnal awakenings. FEV1 improved 13.1 percent with inhaled beclomethasone, compared with an improvement of 7.4 percent with oral montelukast. Beclomethasone had a larger mean effect than montelukast. The reduction in asthma attacks was similar in the beclomethasone and montelukast groups, and both active treatment groups showed significantly reduced eosinophil counts. Clinical adverse events were similar in all three groups.
The authors conclude that oral montelukast and inhaled beclomethasone provide similar protection against worsening episodes of asthma. Both are generally well tolerated. Although there was similar compliance in all groups in this study, data suggest that oral therapy is associated with greater adherence.
In an accompanying editorial, Smith points out that the response to inhaled corticosteroids, the gold standard treatment, may be 70 to 80 percent. It is not clear whether this is due to noncompliance, a lack of effect, poor delivery to the lungs or a combination of these factors. Smith also compared the positive and negative attributes of inhaled corticosteroids and leukotreine receptor antagonists (see the accompanying table). It remains impossible to predict an individual patient's responsiveness to one treatment or the other, and the place for leukotriene receptor antagonists in the treatment of asthma is not yet well defined. Nevertheless, Smith believes that leukotriene receptor antagonists may be a good first choice in patients with mild persistent asthma (symptoms occurring less than daily) based on the safety and oral bioavailability of this class of drugs. In patients with moderate persistent asthma (symptoms occurring daily), inhaled corticosteroids may be a better first choice because of the higher likelihood that they will be effective. In patients with severe persistent asthma (continuous symptoms), the addition of antileukotrienes to treatment with corticosteroids (inhaled and oral) and long-acting beta agonists may be beneficial.