Reducing the Intensity of Treatment in Mild Asthma

Two randomized trials demonstrate the feasibility of step-down therapy in patients whose asthma is well controlled.

Many patients with mild asthma take standard daily doses of inhaled corticosteroids indefinitely. Two new industry-supported, placebo-controlled, randomized trials — each with about 500 participants whose mild asthma was controlled with twice-daily inhaled steroids — show that "step-down" therapy may be reasonable for such patients.

One study compared twice-daily inhaled steroid therapy with once-daily oral or inhaled alternatives. Patients received one of three treatments: inhaled fluticasone (Flovent Diskus, 100 µg), twice daily; combined fluticasone/salmeterol (Advair Diskus, 100/50 µg), once daily in the evening; or oral montelukast (Singulair), once daily. At 16 weeks, treatment failure (an endpoint that included several clinical and spirometric outcomes) had occurred in 20% of patients in each inhaled-therapy group and in 30% of montelukast patients, a significant difference. This difference reflected primarily spirometric outcomes, and not differences in need for systemic steroids or urgent asthma care.

The second study examined the relatively novel idea that as-needed inhaled steroids might be as effective as daily maintenance therapy. Patients received one of four treatments: twice-daily inhaled beclomethasone (250 µg) with as-needed albuterol; twice-daily combined beclomethasone/albuterol, with as-needed albuterol; the same beclomethasone/albuterol combination, but only as needed; and as-needed albuterol only. At 6 months, the primary outcome — morning peak expiratory flow rate — was similar in the twice-daily beclomethasone and the as-needed beclomethasone/albuterol groups, and was significantly higher in both groups than in the as-needed albuterol group. Both twice-daily beclomethasone and as-needed beclomethasone/albuterol were associated with fewer exacerbations than as-needed albuterol.

Comment: These important trials demonstrate the feasibility of step-down therapy in patients whose mild persistent asthma is well controlled with standard twice-daily inhaled corticosteroids. An objective of this research is to minimize cumulative lifetime exposure to inhaled steroids, which may have systemic effects after years of use. The first trial shows that once-daily montelukast or a once-daily combination of an inhaled steroid plus salmeterol are both reasonable alternatives (although treatment failures occurred somewhat more frequently with montelukast). In the second trial, symptom-driven inhaled corticosteroids worked as well as daily therapy in patients with mild asthma.

— Allan S. Brett, MD

Published in Journal Watch General Medicine May 16, 2007
http://content.nejm.org/cgi/content/full/356/20/2040