Israel E, Chervinsky PS, Friedman B, et al. J Allergy Clin Immunol. 2002;110:847–854
Purpose of the Study.
The primary objective of asthma therapy is the maintenance of asthma control, and the most common measures of such control in clinical studies reflect pulmonary function; forced expiratory volume in 1 second (FEV1) is often used. The authors sought to use a different parameter, ie, days of asthma control, as the primary measure, because observations regarding the need for both rescue medications and unscheduled asthma-related health care are central to perceived wellness.
This multicenter study involved 782 individuals, ≥15 years of age, with a ≥1-year history of moderate persistent asthma (baseline FEV1: 50–85% of predicted values) but no controller therapy at the time of enrollment. All patients were required to have a current daily need for inhaled albuterol and documented airway reversibility of ≥15% at the time of entry.
Patients were randomly assigned to receive montelukast (10 mg, each evening), beclomethasone (200 μg, twice daily), or placebo, with a ratio of 3:3:1. The use of spacers was not required. Compliance was monitored with pill counts and simple patient reports of inhaler use. A day of asthma control was defined as a day with no more than 2 puffs of albuterol treatment, no nocturnal awakenings with asthma, and no need for acute medical attention. An asthma exacerbation was defined as ≥3 consecutive days without asthma control. An occurrence of sustained asthma control was defined as ≥3 consecutive days with control. Subjects completed diary cards during the 2-week, single-blind, run-in period and during the 6-week, double-blind, treatment phase. The primary measure was the percentage of days of asthma control during the treatment phase. Secondary measures included average daily albuterol use, percentages of patients with and without attacks, asthma exacerbations, occurrence of sustained asthma control, rescue corticosteroid use, and changes in FEV1 from baseline values. Clinic visits occurred every 3 weeks during the double-blind phase, and spirometry was performed at that time.
The mean percentages of days of asthma control for patients who received montelukast or beclomethasone were similar and were significantly better than that for placebo recipients. Both drugs resulted in significant improvements in FEV1, but the benefit was greater with beclomethasone. There was no difference between the active treatment groups in any of the other secondary measures, and both treatments were clearly superior to placebo for most parameters.
Montelukast and beclomethasone were of similar efficacy, as judged by indices of clinical control other than FEV1. The latter parameter may underestimate clinical effectiveness.
Considering the severity of asthma among these individuals, it might seem surprising that these drugs performed so similarly during the 6-week active treatment phase. One might be tempted to attribute this to presumed poor compliance with the inhaled corticosteroid, compared with the convenient montelukast tablet, especially because beclomethasone monitoring was through reports alone. However, there is no doubt that beclomethasone outperformed the leukotriene receptor antagonist in FEV1 measures, suggesting reasonable compliance and greater potency in improving pulmonary function. Six weeks is probably too short a period to detect differences in major attacks between the 2 treatment groups, and it is likely that a much longer treatment period would have revealed more favorable results for most parameters, including the primary measure, for the inhaled corticosteroid-treated group. Almost by definition, most of these patients had asthma that was too severe to be treated with just 1 drug; a more interesting comparison would have been among patients with mild persistent disease, without histories of hospitalization or recurrent acute attacks.