Long-Acting β2-Agonist Monotherapy vs Continued Therapy With Inhaled Corticosteroids in Patients With Persistent Asthma: A Randomized Controlled Trial

• Published in: JAMA : the journal of the American Medical Association 2001-05, Vol.285 (20), p.2583-2593
• Main Authors: Lazarus, Stephen C, Boushey, Homer A, Fahy, John V, Chinchilli, Vernon M, Lemanske, Jr, Robert F, Sorkness, Christine A, Kraft, Monica, Fish, James E, Peters, Stephen P, Craig, Timothy, Drazen, Jeffrey M, Ford, Jean G, Israel, Elliot, Martin, Richard J, Mauger, Elizabeth A, Nachman, Sami A, Spahn, Joseph D, Szefler, Stanley J, for the Asthma Clinical Research Network of the National Heart, Lung, and Blood Institute
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Medical sciences; Pharmacology. Drug treatments; Respiratory system
• ISSN: 0098-7484; 1538-3598
• DOI: 10.1001/jama.285.20.2583

CONTEXT Long-acting β2-agonists are prescribed for patients with persistent asthma and are sometimes used without inhaled corticosteroids (ICSs). No evidence exists, however, to support their use as monotherapy in adults with persistent asthma. OBJECTIVE To examine the effectiveness of salmeterol xinafoate, a long-acting β2-agonist, as replacement therapy in patients whose asthma is well controlled by low-dose triamcinolone acetonide, an ICS. DESIGN AND SETTING A 28-week, randomized, blinded, placebo-controlled, parallel group trial conducted at 6 National Institutes of Health–sponsored, university-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 µg twice per day). INTERVENTIONS Patients were randomly assigned to continue triamcinolone therapy (400 µg twice per day; n = 54) or switch to salmeterol (42 µg twice per day; n = 54) or to placebo (n = 56) for 16 weeks, after which all patients received placebo for an additional 6-week run-out period. MAIN OUTCOME MEASURES Change in morning and evening peak expiratory flow (PEF), forced expiratory volume in 1 second (FEV1), self-assessed asthma symptom scores, rescue albuterol use, asthma-specific quality-of-life scores, treatment 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 differences between the salmeterol and triamcinolone groups were observed for conventional outcomes of clinical studies of asthma therapy—morning PEF, evening PEF, asthma symptom scores, rescue albuterol sulfate use, or quality of life. Both active treatments were superior to placebo. However, the salmeterol 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