Inhaled Combined Budesonide–Formoterol as Needed in Mild Asthma

Background In patients with mild asthma, as‐needed use of an inhaled glucocorticoid plus a fast‐acting β2‐agonist may be an alternative to conventional treatment strategies. Methods We conducted a 52‐week, double‐blind trial involving patients 12 years of age or older with mild asthma. Patients were randomly assigned to one of three regimens: twice‐daily placebo plus terbutaline (0.5 mg) used as needed (terbutaline group), twice‐daily placebo plus budesonide–formoterol (200 μg of budesonide and 6 μg of formoterol) used as needed (budesonide–formoterol group), or twice‐daily budesonide (200 μg) plus terbutaline used as needed (budesonide maintenance group). The primary objective was to investigate the superiority of as‐needed budesonide–formoterol to as‐needed terbutaline with regard to electronically recorded weeks with well‐controlled asthma. Results A total of 3849 patients underwent randomization, and 3836 (1277 in the terbutaline group, 1277 in the budesonide–formoterol group, and 1282 in the budesonide maintenance group) were included in the full analysis and safety data sets. With respect to the mean percentage of weeks with well‐controlled asthma per patient, budesonide–formoterol was superior to terbutaline (34.4% vs. 31.1% of weeks; odds ratio, 1.14; 95% confidence interval [CI], 1.00 to 1.30; P=0.046) but inferior to budesonide maintenance therapy (34.4% and 44.4%, respectively; odds ratio, 0.64; 95% CI, 0.57 to 0.73). The annual rate of severe exacerbations was 0.20 with terbutaline, 0.07 with budesonide–formoterol, and 0.09 with budesonide maintenance therapy; the rate ratio was 0.36 (95% CI, 0.27 to 0.49) for budesonide–formoterol versus terbutaline and 0.83 (95% CI, 0.59 to 1.16) for budesonide–formoterol versus budesonide maintenance therapy. The rate of adherence in the budesonide maintenance group was 78.9%. The median metered daily dose of inhaled glucocorticoid in the budesonide–formoterol group (57 μg) was 17% of the dose in the budesonide maintenance group (340 μg). Conclusions In patients with mild asthma, as‐needed budesonide–formoterol provided superior asthma‐symptom control to as‐needed terbutaline, assessed according to electronically recorded weeks with well‐controlled asthma, but was inferior to budesonide maintenance therapy. Exacerbation rates with the two budesonide‐containing regimens were similar and were lower than the rate with terbutaline. Budesonide–formoterol used as needed resulted in substantially lower glucocorticoid exposure than budesonide maintenance therapy. (Funded by AstraZeneca; SYGMA 1 ClinicalTrials.gov number, NCT02149199.)