Maintenance plus reliever budesonide/formoterol compared with a higher maintenance dose of budesonide/formoterol plus formoterol as reliever in asthma: an efficacy and cost-effectiveness study

Objective: To evaluate efficacy and cost-effectiveness of budesonide/formoterol (Symbicort*) maintenance (one dose once or twice daily) plus additional doses as needed (Symbicort Maintenance And Reliever Therapy, SMART) compared with a higher fixed dose of budesonide/ formoterol with formoterol as needed in patients with persistent asthma. Study design and methods: 6-month, open, randomised study of 465 patients either not well controlled on an inhaled corticosteroid (ICS), or well controlled on a combination of ICS and a long-acting beta(2)-agonist (LABA). Treatments: budesonide/ formoterol 160/4.5 mu g, one inhalation, once or twice daily maintenance plus additional doses as- needed (1 x SMART or 2 x SMART), or budesonide/ formoterol 160/4.5 mu g two inhalations twice daily plus formoterol 4.5 mu g as needed (2 x 2 FIX + F). Children 6-11 years old used an 80/4.5 mu g dose strength. Primary variables of efficacy were the changes in the Asthma Control Questionnaire (ACQ(5)) and morning peak expiratory flow (PEF). Results: Mean age of patients 40 years (range 6-82 years); 53% female. No differences between the groups were found in ACQ(5) scores or asthma exacerbation rates. Morning PEF was higher in the 2 x 2 FIX + F group vs. the 1 x SMART and 2 x SMART groups ( differences 13L/min and 9 L/min, respectively; p < 0.002). The 1 x SMART group showed a significant decrease in asthma controlled days compared with the two other groups. No difference was seen between the 2 x SMART group and the 2 x 2 FIX + F group. Treatment costs were significantly lower in the SMART groups compared with the 2 x 2 FIX + F group. Conclusion: Compared with the 2 x 2 FIX + F treatment the use of budesonide/formoterol was 30-40% lower in the SMART groups while maintaining equal ACQ5 scores. Daily asthma control improved equally with 2 x SMART compared to 2 x 2 FIX + F with a reduction in asthma medication cost. The one dose once daily maintenance treatment (1 x SMART) resulted in a low level of treatment failure (exacerbations) but led to more days with symptoms. Therefore, a daily dose of two inhalations seems to be the lowest appropriate dose in patients with moderate persistent asthma