Purpose of the Study. To compare inhaled salmeterol powder to oral montelukast in patients with persistent asthma who are not well-controlled on inhaled corticosteroids (ICS).
Study Population. Male and nonlactating, nonpregnant females ≥15 years of age with the diagnosis of asthma for at least 6 months were recruited from 71 private and university clinics in the United States and Puerto Rico. The group included 948 subjects (61% female, 85% Caucasian). All subjects were symptomatic with their asthma for at least 6 weeks before screening and at a constant dose of ICS for 30 days before screening. Baseline forced expiratory volume in 1 second (FEV1) was 50% to 80% and all subjects had at least 12% improvement in FEV1 postbronchodilator.
Methods. Two multicenter, randomized, double-blind, parallel-group clinical trials were conducted comparing 50 μg bid of salmeterol by dry powder inhaler (n = 476) versus 10 mg po daily of montelukast (n = 472). All subjects underwent baseline history and physical, and pulmonary function tests including FEV1 reversibility. After a 7- to 14-day run-in period to assess symptoms, diary card completion, and patient proficiency with inhaler use, patients whose FEV1 remained within 50% to 80% of normal were eligible for enrollment. Subjects also had to meet at least 1 of the following criteria during the 7 days before randomization: use of an average of ≥4 puffs per day of albuterol, a symptom score of ≥2 on ≥3 days, and/or ≥3 nights of nocturnal asthma symptoms. The subjects remained on their current ICS dose throughout the study and rescue albuterol, but no other asthma medications were allowed other than study drug. Subjects were asked to record am and pm peak flows (PEF), nocturnal awakenings, albuterol use, asthma symptoms, and daily study drug use. Symptoms were rated using a 5-point scale and were targeted to affects on activity level. Subjects returned for assessments at 1, 4, 8, and 12 weeks of treatment. The subjects completed a satisfaction survey at the end of the 12-week study.
Results. A total of 476 subjects received inhaled salmeterol and 472 received montelukast. The treatment groups had similar demographics and disease characteristics at baseline, with 61% women, >80% Caucasian, >70% with asthma ≥10 years, mean baseline FEV1 68% of predicted, and mean baseline PEF of 370 l/m. Morning PEF in the salmeterol treated group increased more significantly (mean = 35 l/m) than the montelukast treated group (mean = 21.7 l/m). The bronchodilator properties of salmeterol were superior than montelukast over all treatment weeks. Patients in the salmeterol group had a significantly greater increase in symptom-free days than the montelukast group (24% vs 16%; P < .001). Symptom scores for all parameters except wheezing were significantly improved in the salmeterol group vs the montelukast group. Subjects in the salmeterol group used significantly less rescue albuterol than the montelukast group. Regarding patient satisfaction with the drug, the salmeterol group had greater satisfaction other than in how long the medication worked, where there was no difference in scores. The number of asthma exacerbations and the number of adverse events was similar in both groups, with 13 in each group withdrawing from the study because of adverse events.
Conclusion. The addition of salmeterol in moderate to severe persistent adult asthmatics poorly controlled on ICS was superior to the addition of montelukast in improvement in PEF and overall symptom control.
Reviewer’s Comments. The addition of inhaled salmeterol in subjects who were not adequately controlled on ICS showed significantly greater improvement in lung function and control of symptoms (other than wheezing) compared with oral montelukast. Other groups have compared salmeterol as an additive agent versus doubling the ICS dose and versus another leukotriene modifier, but not all in that study were on baseline ICS. Future studies are needed to determine if these findings will hold true over longer study periods and whether either long-acting β-agonists or leukotriene modifiers have a bearing on the natural history of asthma. In addition, similar studies in children are needed to see if the same patterns of response occur in all age groups.
- Copyright © 2002 by the American Academy of Pediatrics