Purpose of the Study. To investigate the use of a long-acting β2-agonist (salmeterol) as monotherapy in patients with persistent asthma who had been well-controlled by low-dose inhaled corticosteroids (ICS).
Study Population. Four hundred twenty-two patients ages 12 through 65 years, entered a common 6-week run-in period for 2 companion studies (Salmeterol or Corticosteroids [SOCS] and Salmeterol ± Inhaled Corticosteroids [SLIC]). Three hundred sixty-one patients completed the run-in period of treatment with inhaled triamcinolone acetonide (400 μg twice daily). One hundred sixty-four patients achieved good asthma control according to preestablished clinical and pulmonary function criteria and were entered into the SOCS trial. One hundred seventy-five patients did not achieve good asthma control and were entered into the SLIC trial.
Methods. This was a 28-week, randomized, blinded, placebo-controlled, parallel group trial conducted at 6 National Institutes of Health (NIH)-sponsored, university-based ambulatory care centers over a 2-year period. Patients were randomly assigned to continue ICS therapy (400 μg twice daily; n = 54) or switch to salmeterol monotherapy (42 μg twice daily; (n = 54) or placebo twice daily; (n = 56) for 16 weeks, after which all patients received placebo for an additional 6-week run-out period. Main outcome measures included pulmonary function, asthma symptom scores, quality-of-life scores, treatment failure by preestablished criteria and bronchial reactivity and markers of airway inflammation measured from induced sputum samples and exhaled nitric oxide.
Results. During the 16-week randomized treatment, no significant differences between the salmeterol only and the ICS-only groups were observed for conventional outcomes of clinical studies of asthma therapy including morning peak flow, evening peak flow, asthma symptom scores, rescue albuterol inhaler use, or quality-of-life. Both active treatment groups were superior to placebo, but the salmeterol-only group had more treatment failures (24% vs 6%; P = .004), as well as more asthma exacerbations (20% vs 7%; P = .04). The salmeterol-only group had greater increases in median sputum eosinophils (2.4–10.6% vs -0.7–0.3%; P < .001), greater eosinophilic cationic protein (P = .005) and tryptase levels (P < .001). Deterioration of asthma control in patients who were switched from active treatment (either ICS or salmeterol) to placebo after 22 weeks of randomized therapy was not significantly longer in the ICS versus the salmeterol group.
Conclusions. Patients with persistent asthma, well-controlled by triamcinolone 400 μg twice daily, experienced a clinically significant loss of asthma control and increased inflammatory markers of asthma in induced sputum when switched to salmeterol monotherapy.
Reviewer’s Comments. Although salmeterol can provide significant benefit when used in combination with inhaled steroids, it should not be used as monotherapy for the maintenance of asthma. The results of this study are entirely consistent with the guidelines that stress the need for medications with antiinflammatory activity for all patients with persistent asthma.
- Copyright © 2002 by the American Academy of Pediatrics