Purpose of the Study. To determine whether inhaled corticosteroid (ICS) therapy can be reduced or eliminated in patients with persistent asthma after adding a long-acting β2-agonist to their treatment regimen.
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 24-week, randomized, controlled, blinded, double-dummy, parallel group trial conducted at 6 National Institutes of Health (NIH)-sponsored, university-based ambulatory care centers over a 2-year period. Patients continued on triamcinolone therapy in the same dose of 400 μg twice daily. Blinded, add-on therapy was then done with either placebo (n = 21) or salmeterol 42 μg twice daily (n = 154) for 2 weeks at stable doses. Next was an ICS reduction phase over the next 8 weeks as all 21 patients on triamcinolone plus placebo were assigned to receive half the dose of triamcinolone 200 μg twice daily plus continued placebo (placebo–minus group). Patients on full dose ICS plus salmeterol were randomized to either continue on that same dose (salmeterol–plus group) or to continue on salmeterol with half the dose of ICS 200 μg daily (salmeterol–minus group). Last was an 8-week ICS elimination phase. The placebo–minus group (previously on ICS 200 μg bid plus placebo salmeterol) were assigned to receive placebo ICS and placebo salmeterol. The salmeterol–minus group (receiving a half dose of ICS plus salmeterol) were changed to placebo ICS plus salmeterol. The salmeterol–plus group (receiving a full dose of ICS plus a full dose of salmeterol) continued on that same dose (active control group). The main outcome measure was timed to asthma treatment failure (specifically defined by parameters of pulmonary function and/or clinical deterioration) in patients receiving salmeterol.
Results. Treatment failure occurred in 8.3% of the salmeterol–minus group 8 weeks after ICS treatment was reduced compared with 2.8% of the salmeterol–plus group (active control group, full dose) when the dose of ICS was not changed. Subsequent treatment failure occurred in 46.3% of the salmeterol–minus group 8 weeks after ICS therapy was eliminated compared with 13.7% of the salmeterol–plus group (active control group, full dose). The relative risk of treatment failure at the end of the ICS elimination phase in the salmeterol–minus group (plus placebo ICS) was 4.3% compared with the salmeterol–plus group (active control group, full dose). Secondary outcome measures included a lower mean presalmeterol forced expiratory volume in 1 second (FEV1) in the salmeterol–minus group versus the salmeterol–plus group and decreased salmeterol-protected methacholine response was less in the salmeterol minus versus the salmeterol plus group.
Conclusions. In patients with persistent asthma suboptimally controlled by triamcinolone therapy alone, but whose asthma symptoms improve after addition of salmeterol, a 50% reduction in ICS dose can occur without a significant loss of asthma control. However, total elimination of ICS therapy results in a significant deterioration of asthma control as well as decline in pulmonary function and loss of bronchoprotection.
Reviewer’s Comments. This study is entirely consistent with the current consensus that although salmeterol may improve asthma control when given along with an inhaled steroid and provide significant steroid-sparing effects. In addition, it supports the notion that salmeterol should not be used as monotherapy for persistent asthma.
- Copyright © 2002 by the American Academy of Pediatrics