Overall asthma control achieved with budesonide/formoterol maintenance and reliever therapy for patients on different treatment steps

Abstract

Background: Adjusting medication for uncontrolled asthma involves selecting one of several options from the same or a higher treatment step outlined in asthma guidelines. We examined the relative benefit of introducing budesonide/formoterol (BUD/FORM) maintenance and reliever therapy (Symbicort SMART® Turbuhaler®) in patients previously prescribed treatments from Global Initiative for Asthma (GINA) Steps 2, 3 or 4.

Methods: This is a post hoc analysis of the results of five large clinical trials (>12000 patients) comparing BUD/FORM maintenance and reliever therapy with other treatments categorised by treatment step at study entry. Both current clinical asthma control during the last week of treatment and exacerbations during the study were examined.

Results: At each GINA treatment step, the proportion of patients achieving target levels of current clinical control were similar or higher with BUD/FORM maintenance and reliever therapy compared with the same or a higher fixed maintenance dose of inhaled corticosteroid/long-acting β2-agonist (ICS/LABA) (plus short-acting β2-agonist [SABA] as reliever), and rates of exacerbations were lower at all treatment steps in BUD/FORM maintenance and reliever therapy versus same maintenance dose ICS/LABA (P < 0.01) and at treatment Step 4 versus higher maintenance dose ICS/LABA (P < 0.001). BUD/FORM maintenance and reliever therapy also achieved significantly higher rates of current clinical control and significantly lower exacerbation rates at most treatment steps compared with a higher maintenance dose ICS + SABA (Steps 2-4 for control and Steps 3 and 4 for exacerbations). With all treatments, the proportion of patients achieving current clinical control was lower with increasing treatment steps.

Conclusions: BUD/FORM maintenance and reliever therapy may be a preferable option for patients on Steps 2 to 4 of asthma guidelines requiring a more effective treatment and, compared with other fixed dose alternatives, is most effective in the higher treatment steps.

Figure 1

Proportion of Controlled or Partly Controlled asthma patients in final week of treatment by study treatment and GINA treatment step at entry. BUD/FORM = budesonide/formoterol; ICS = inhaled corticosteroid; LABA = long-acting β₂-agonist; OR = odds ratio; SABA = short-acting β₂-agonist

Figure 2

Mean FEV₁ by visit and GINA step at study entry. BUD/FORM maintenance and reliever therapy vs. higher maintenance dose ICS + SABA, difference at last visit as percentage predicted normal, adjusted for FEV₁ at randomisation visit (95% confidence interval): Step 2, 2.18 (0.22, 4.14); Step 3, 3.58 (2.29, 4.87); Step 4, 3.83 (2.25, 5.40). BUD/FORM maintenance and reliever therapy vs. same maintenance dose ICS/LABA + SABA, difference at last visit as percentage predicted normal, adjusted for FEV₁ at randomisation visit (95% confidence interval): Step 2, 1.29 (-1.29, 3.88); Step 3, 2.50 (1.25, 3.76); Step 4, 2.70 (1.24, 4.17). BUD/FORM maintenance and reliever therapy vs. higher maintenance dose ICS/LABA + SABA, difference at last visit as percentage predicted normal, adjusted for FEV₁ at randomisation visit (95% confidence interval): Step 3, 0.22 (-0.82, 1.26); Step 4, 0.53 (-0.57, 1.64).

Figure 3

Exacerbation rate by study treatment and GINA treatment step at study entry. BUD/FORM = budesonide/formoterol; ICS = inhaled corticosteroid; LABA = long-acting β₂-agonist; SABA = short-acting β₂-agonist BUD/FORM maintenance and reliever therapy vs. higher maintenance dose ICS + SABA, exacerbation rate ratio (95% confidence interval): Step 2, 0.829 (0.570, 1.207); Step 3, 0.431 (0.353, 0.526); Step 4, 0.624 (0.512, 0.761). BUD/FORM maintenance and reliever therapy vs. same maintenance dose ICS/LABA + SABA, exacerbation rate ratio (95% confidence interval): Step 2, 0.583 (0.389, 0.874); Step 3, 0.455 (0.371, 0.558); Step 4, 0.519 (0.434, 0.620). BUD/FORM maintenance and reliever therapy vs. higher maintenance dose ICS/LABA + SABA, exacerbation rate ratio (95% confidence interval): Step 3, 0.795 (0.631, 1.002); Step 4, 0.665 (0.549, 0.807).

Figure 4

Time to first severe exacerbation by GINA treatment step at study entry. BUD/FORM = budesonide/formoterol; ICS = inhaled corticosteroid; LABA = long-acting β₂-agonist; SABA = short-acting β₂-agonist P-values refer to Cox model. BUD/FORM maintenance and reliever therapy vs. higher maintenance dose ICS + SABA, hazard ratio (95% confidence interval): Step 2, 0.545 (0.341, 0.870); Step 3, 0.507 (0.401, 0.642); Step 4, 0.701 (0.546, 0.900). BUD/FORM maintenance and reliever therapy vs. same maintenance dose ICS/LABA + SABA, hazard ratio (95% confidence interval): Step 2, 0.467 (0.268, 0.814); Step 3, 0.516 (0.406, 0.656); Step 4, 0.561 (0.449, 0.700). BUD/FORM maintenance and reliever therapy vs. higher maintenance dose ICS/LABA + SABA, hazard ratio (95% confidence interval): Step 3, 0.726 (0.554, 0.950); Step 4, 0.773 (0.620, 0.965).