The SMILE Study

Design

The SMILE study by Rabe and colleagues [1] was a randomised, double-blind, 12-month, parallel-group study comparing the efficacy and safety of Symbicort® maintenance therapy with three different reliever medications – Symbicort, formoterol and terbutaline.

The primary efficacy variable was time to first severe exacerbation. The study enrolled 3994 patients with asthma (aged > 12 years) who were symptomatic on regular inhaled corticosteroid/long-acting ß2-agonist (ICS/LABA) maintenance therapy. Following a 2-week run in, patients received Symbicort maintenance therapy (160/4.5 μg one inhalation twice daily) plus one of the three alternative as-needed medications – Symbicort (160/4.5 μg), formoterol (4.5 μg) or terbutaline (0.4 mg).

Results

The SMILE study showed that as-needed Symbicort provides greater protection from asthma exacerbations than as-needed terbutaline or formoterol, suggesting that both the budesonide and formoterol components of Symbicort play an important role in the efficacy of Symbicort SMART®.

• Symbicort plus as-needed Symbicort (Symbicort SMART) prolonged the time to first severe exacerbation versus as-needed formoterol (P = 0.0048) or as-needed terbutaline (P < 0.0001).
• Symbicort SMART also reduced the rate of severe exacerbations by 27% compared with as- needed formoterol (P = 0.0038) and by 45% versus terbutaline (P < 0.0001). The rate of exacerbations requiring hospitalisation/emergency room treatment was reduced by 27–39% with Symbicort SMART versus the two comparators.
• Patients receiving Symbicort SMART used fewer as-needed inhalations per day (1.02) compared with those receiving formoterol (1.23) or terbutaline (1.26) as needed. On 52% of days, patients in the Symbicort SMART arm did not require any reliever medication compared with 48% in either of the other as-needed treatment groups.
• Symbicort SMART significantly improved forced expiratory volume in 1 second, increased average morning and evening peak expiratory flow and improved asthma scores assessed by the asthma control questionnaire compared with as-needed formoterol and terbutaline (all P < 0.05).
• All treatments were well tolerated and the incidence of adverse events was similar across all groups.

References

1. Rabe KF, Atienza T, Magyar P, et al. Effect of budesonide in combination with formoterol for reliever therapy in asthma exacerbations: a randomised controlled, double-blind study. Lancet 2006; 368:744–753.