Chest
Volume 134, Issue 6, December 2008, Pages 1192-1199
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Original Research
Asthma
Increasing Doses of Inhaled Corticosteroids Compared to Adding Long-Acting Inhaled β2-Agonists in Achieving Asthma Control

https://doi.org/10.1378/chest.08-1018Get rights and content

Background

Combination therapy with inhaled corticosteroids (ICSs) and long-acting β2-agonists (LABAs), or treatment with high doses of ICSs alone improves asthma control when therapy with low-dose ICSs is not sufficient. However, it is not known which of these treatment options is more effective in sustaining asthma control.

Objectives

To evaluate the effect of increasing the ICS dosage vs adding LABAs on the time spent with well-controlled asthma or poorly controlled asthma.

Methods

Post hoc analysis of the Formoterol and Corticosteroid Establishing Therapy study, which compared a fourfold increase in the budesonide dose with and without formoterol.

Results

Time with well-controlled asthma was improved by 19% (95% confidence interval [CI], 3 to 35%; p = 0.017) by adding formoterol, 24 μg/d, to therapy with budesonide, 200 μg/d, compared to 2% (95% CI, −9 to 12%; p = 0.76) with therapy with budesonide, 800 μg/d, alone. Time with well-controlled asthma was further improved by 29% (95% CI, 13 to 47%; p < 0.001) by adding formoterol to therapy with budesonide, 800 μg/d. Time with poorly controlled asthma was significantly reduced using the same interventions by 43% (95% CI, 25 to 57%), 22% (95% CI, 7 to 44%), and 50% (95% CI, 30 to 64%), respectively. Adding formoterol to budesonide was significantly more effective in increasing time with well-controlled asthma when compared to increasing the budesonide dose fourfold (increase, 16%; 95% CI, 1 to 33%; p = 0.035), with a trend for a greater reduction in time with poor control (decrease, 21%; 95% CI, −5 to 42%).

Conclusion

The addition of formoterol to therapy with low-dose budesonide increases the probability of well-controlled asthma compared to a substantial increase in the dose of an ICS.

Section snippets

Study Design

Patients and study design have been described in detail elsewhere.5 Eligible patients were randomly assigned to one of the following regimens (administered twice daily) for 12 months: 100 μg of budesonide plus placebo (Bud 200 μg/d); 100 μg of budesonide plus 12 μg of formoterol (daily dose, 24 μg) [Oxis; AstraZeneca; Lund, Sweden] (Bud 200 μg/d + Form); 400 μg of budesonide plus placebo (Bud 800 μg/d); and 400 μg of budesonide plus 12 μg of formoterol (daily dose, 24 μg) [Bud 800 μg/d + Form].

Results

Of the 1,114 patients entering the run-in period, 262 were excluded from the study before randomization because they did not meet the randomization criteria. The remaining 852 patients were randomly assigned to treatment. Baseline demographic characteristics are presented in Table 1. The differences in baseline data among the groups were minor. During the budesonide run-in period with a dose of 800 μg twice daily, the mean use of as-needed rescue medication and the incidence of awakenings

Discussion

The aim of this post hoc analysis of the FACET data set was to clarify the role of increasing ICS doses, with and without LABA therapy, in increasing the time spent with well-controlled asthma and in reducing the time spent with poorly controlled asthma. To achieve this, we focused, for the first time, on both good and bad composite control of asthma. This revealed a clear benefit for both LABAs and higher doses of ICSs in stabilizing asthma control. Our findings confirm that in patients with

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The FACET study was supported by AstraZeneca R&D (Lund, Sweden).

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).

1

Drs. O'Byrne, Postma, and Barnes have been consultants to AstraZeneca, and have received speakers fees and grants-in-aid from AstraZeneca.

2

Mr. Naya and Dr. Kallen are employed by AstraZeneca and own stock.

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