The AHEAD Study

Design

The AHEAD study by Bousquet and colleagues [1] was a randomised, double-blind, 6-month, parallel group study comparing the safety and efficacy of Symbicort SMART® with salmeterol/fluticasone (Seretide™) plus a short-acting β2-agonist (SABA), at its highest approved maintenance dose.

The study randomised 2309 symptomatic adults and adolescents (aged 12–80 years, forced expiratory volume in 1 second [FEV1] ≥50% predicted normal) with persistent asthma to receive Symbicort SMART (160/4.5 µg two inhalation twice daily plus as needed) or Seretide™ (50/500 µg one inhalation twice daily plus as-needed terbutaline) or Symbicort. The primary variable was time to first severe exacerbation.

Results

The AHEAD study showed that Symbicort SMART reduces the incidence of severe asthma exacerbations and hospitalisation/emergency room (ER) treatment with similar daily symptom control compared with sustained high-dose Seretide plus SABA. This benefit is achieved with substantially less exposure to inhaled corticosteroids.

• Time to first severe exacerbation was not significantly prolonged with Symbicort SMART (risk ratio 0.82; P = 0.12).
• However, Symbicort SMART significantly reduced the rate of total exacerbations by 21% (from 31 to 25 events/100 patients/year; P = 0.039), and exacerbations requiring hospitalisation/emergency room treatment by 31% (from 13 to 9 events/100 patients/year; P = 0.046) compared with Seretide. This was achieved at a lower mean ICS dose (792 µg/day budesonide [1238 µg/day beclomethasone dipropionate (BDP) equivalent] versus 1000 µg/day fluticasone [2000 µg/day BDP equivalent] with Seretide; P < 0.0001).
• Patients treated with Symbicort SMART had a lower number of days with high as-needed reliever compared with higher maintenance dose Seretide plus SABA. The incidence of severe exacerbations in association with this pattern of high as-needed use was reduced to a greater extent with Symbicort SMART than with higher maintenance dose Seretide plus SABA, suggesting that Symbicort SMART provides added protection against exacerbations for symptomatic asthma patients.
• Improvements in lung function (FEV1), asthma control questionnaire scores and asthma control days were similar in both treatment groups.
• Both treatments were well tolerated.

References

1. Bousquet J, Boulet LP, Peters MJ, et al. Budesonide/formoterol for maintenance and relief in uncontrolled asthma versus high-dose salmeterol/fluticasone. Respir Med 2007; 101:2437–2446.