Asthma Exacerbation Risk With As-Needed Budesonide-Formoterol vs Maintenance Budesonide

Asthma inhaler and medicine, pills
Asthma inhaler and medicine, pills
Budesonide-formoterol as needed was not inferior compared with budesonide maintenance therapy in terms of severe asthma exacerbation rates, but may be inferior for controlling symptoms.

The use of budesonide-formoterol as needed in patients with mild asthma may not be inferior to twice-daily budesonide as it relates to the rate of severe asthma exacerbations, but may be inferior for symptom control, according to a study published in the New England Journal of Medicine.

Researchers conducted a 52-week, double-blind, multicenter (354 sites in 25 countries) randomized trial (SYGMA 2; Identifier: NCT02224157) that included individuals aged 12 years and older with mild asthma. Individuals were randomly assigned to receive either twice-daily placebo plus budesonide-formoterol as needed (n=2089) or budesonide maintenance therapy with twice-daily budesonide plus terbutaline as needed (n=2087).

The purpose of the study was to compare the rate of severe exacerbations in individuals treated with budesonide-formoterol as needed with those treated with budesonide maintenance therapy. In addition, the Asthma Control Questionnaire-5 (ACQ5) was used to assess symptoms in all participants. A total of 94.1% of individuals completed the trial, with 90.8% completing treatment.

Treatment with budesonide-formoterol as needed was noninferior to budesonide maintenance therapy regarding the rate of severe exacerbations, with annual rates of 0.11 and 0.12, respectively (95% CI, 0.10-0.13 and 0.10-0.14, respectively) and a rate ratio of 0.97 (upper 1-sided 95% CI, 1.16). There was no difference between groups in adherence to maintenance regimen, with a 64.0%±30.0% and 62.8%±29.4% average percentage of placebo and budesonide maintenance doses, respectively. However, treatment with budesonide-formoterol was inferior to treatment with budesonide maintenance regarding symptom management, as individuals treated with budesonide-formoterol had fewer recorded days of no use of as-needed medications compared with the budesonide maintenance group (69.0% vs 75.9%).

In addition, fewer patients in the budesonide-formoterol had a decrease in ASQ5 from baseline compared with those in the budesonide maintenance group who had a decrease in ASQ5 score of ≥0.5 units (40.3% vs 44.3%; odds ratio, 0.86; 95% CI, 0.75-0.99).

Researchers concluded that despite being inferior to budesonide maintenance therapy in symptom control, the rate of severe exacerbations with budesonide-formoterol was not inferior to budesonide maintenance therapy using an inhaled glucocorticoid dose 75% lower than in the 1 used in the budesonide maintenance group. However, improvements in quality of life, control of asthma symptoms, and FEV1 before bronchodilator were larger in individuals treated with budesonide maintenance therapy. Similar findings were reported in the SYGMA 1 trial.

Related Articles

Clinicians should consider the use of budesonide-formoterol in individuals with mild asthma because the rate of severe exacerbations was not inferior to budesonide maintenance therapy while containing a significantly lower amount of inhaled glucocorticoids, but should also consider the increased use of as needed medications when placing an individual on this treatment plan.


Bateman ED, Reddel HK, O’Byrne PM, et al. As-needed budesonide-formoterol versus maintenance budesonide in mild asthma. N Engl J Med. 2018;378(20):1877-1887.