Long-acting beta(2)-agonist monotherapy vs continued therapy with inhaled corticosteroids in patients with persistent asthma - A randomized controlled trial

Context Long-acting beta (2)-agonists are prescribed for patients with pers istent asthma and are sometimes used without inhaled corticosteroids (ICSs) . No evidence exists, however, to support their use as monotherapy in adult s with persistent asthma. Objective To examine the effectiveness of salmeterol xinafoate, a long-acti ng beta (2)- agonist, as replacement therapy in patients whose asthma is we ll controlled by low-dose triamcinolone acetonide, an ICS. Design and Setting A 28-week, randomized, blinded, placebo-controlled, para llel group trial conducted at 6 National Institutes of Health-sponsored, un iversity-based ambulatory care centers from February 1997 to January 1999. Participants One hundred sixty-four patients aged 12 through 65 years with persistent asthma that was well controlled during a 6-week run-in period of treatment with inhaled triamcinolone (400 mug twice per day). Interventions Patients were randomly assigned to continue triamcinolone the rapy (400 mug twice per day; n = 54) or switch to salmeterol (42 mug twice per day; n = 54) or to placebo (n = 56) for 16 weeks, after which all patie nts received placebo for an additional 6-week run-out period. Main Outcome Measures Change in morning and evening peak expiratory flow (P EF), forced expiratory volume in 1 second (FEV1), self-assessed asthma symp tom scores, rescue albuterol use, asthma-specific quality-of-life scores, t reatment failure, asthma exacerbation, bronchial reactivity, and markers of airway inflammation, compared among the 3 treatment groups. Results During the 16-week randomized treatment period, no significant diff erences between the salmeterol and triamcinolone groups were observed for c onventional outcomes of clinical studies of asthma therapy-morning PEF, eve ning PEF, asthma symptom scores, rescue albuterol sulfate use, or quality o f life. Both active treatments were superior to placebo. However, the salme terol group had more treatment failures than the triamcinolone group (13/54 [24%] vs 3/54 [6%]; P=.004), as well as more asthma exacerbations (11/54 [ 20%] vs 4/54 [7%]; P=.04), greater increases in median (interquartile range ) sputum eosinophils (2.4% [0.0% to 10.6%] vs -0.1% [-0.7% to 0.3%]; P<.001 ), eosinophil cationic protein (71 [-2 to 430] U/L vs -4 [-31 to 56] U/L; P =.005), and tryptase (3.1 [2.1 to7.6] ng/mL vs 0.0 [0.0 to 0.7] ng/mL; P<.0 01). The duration of benefit when patients were switched from active treatm ent to placebo after 22 weeks of randomized treatment was not significantly longer in the triamcinolone group than in the salmeterol group. Conclusions Patients with persistent asthma well controlled by low doses of triamcinolone cannot be switched to salmeterol monotherapy without risk of clinically significant loss of asthma control.