Background: Asthma management often involves using multiple medications to achieve optimal control, then stepping down the doses as tolerated. Most trials of step-down therapy include patients with moderate to severe asthma and use the lowest possible doses of inhaled corticosteroids to adequately control symptoms. Patients with mild, persistent asthma may benefit from less medication, but a consistent protocol for these patients has yet to be established. The American Lung Association Asthma Clinical Research Centers (ALA-ACRC) investigated potential alternatives for step-down therapy in patients with mild, persistent asthma.

The Study: The double-blind trial included patients recruited from 19 ALA-ACRC clinics. Inclusion criteria were asthma satisfactorily controlled with inhaled fluticasone (Flovent HFA), 100 mcg twice a day; a baseline forced expiratory volume in one second (FEV₁) of 60 percent or more of the predicted value; and at least a 12 percent improvement in FEV₁ after bronchodilator therapy or a 20 percent decrease in FEV₁ after a methacholine (Provocholine) challenge. Participants were randomly assigned to a control group that continued inhaled fluticasone twice a day; to fluticasone/salmeterol (Advair Diskus), 100/50 mcg daily; or to montelukast (Singulair), 5 mg daily for children or 10 mg daily for participants 15 years or older.

The study was conducted over 16 weeks. The primary end point was time to treatment failure, defined as requiring further asthma treatment (i.e., hospitalization, urgent care visit, or need for additional inhaled or systemic corticosteroids); 20 percent decline in baseline FEV₁ value; or 35 percent decrease from baseline in morning peak expiratory flow rates.

Results: The study included 500 patients with a mean age of 31 years; 60 percent were women. Adherence to treatment was relatively evenly distributed across the groups.

The montelukast group had a significantly greater treatment failure rate (30.3 percent) than the other groups, but there was no significant difference between the fluticasone and the fluticasone/salmeterol groups (20.2 and 20.4 percent failure rate, respectively). The most common overall reason for treatment failure was a decrease in FEV₁ value of 20 percent or more from baseline, which occurred most often in the montelukast group. Other reasons for treatment failure (i.e., urgent care visits for asthma or symptoms requiring additional corticosteroid use) were less common, and their occurrence was similar across all groups.

Mean FEV₁ values were significantly greater among patients using f luticasone or f luticasone/salmeterol compared with those using montelukast (91.1, 91.8, and 88.8 percent of the predicted value, respectively). Nocturnal asthma symptoms were more commonly reported in the montelukast group, but the number of symptom-free days was similar across groups.

Adverse effect rates were similar across groups and primarily consisted of minor respiratory symptoms. Upper respiratory infections were significantly more common in the fluticasone group (37.5 percent) and the fluticasone/salmeterol group (38.5 percent) compared with the montelukast group (26.7 percent).

Conclusion: Once-daily fluticasone/salmeterol is similarly effective to twice-daily fluticasone for controlling mild, persistent asthma and is a reasonable step-down option. However, the use of montelukast for step-down therapy in this group is associated with greater treatment failure than traditional management.