The use of budesonide-formoterol as needed in patients with mild asthma may be superior to the use of as-needed terbutaline in controlling asthma symptoms, but inferior to twice-daily budesonide, according to a study published by the New England Journal of Medicine.
Researchers conducted a 52-week, double-blind, multicenter randomized trial (SYGMA 1; ClinicalTrials.gov Identifier: NCT02149199) that included individuals 12 years and older with mild asthma. A total of 3836 individuals randomly received twice-daily placebo plus terbutaline (n=1277), twice-daily placebo plus budesonide-formoterol as needed (n=1277), or budesonide maintenance therapy with twice-daily budesonide plus terbutaline as needed (n=1282). The purpose of this study was to assess electronically recorded weeks with well-controlled asthma to investigate the superiority of as-needed budesonide-formoterol to as-needed terbutaline. A total of 87.4% of individuals enrolled in the study completed the trial.
Budesonide-formoterol was superior to as-needed terbutaline (34.4% vs. 31.1% of the weeks; odds ratio [OR], 1.14; 95% CI, 1.00-1.30; P =.046) in controlling asthma symptoms, but inferior to treatment with budesonide maintenance therapy (34.4% vs. 44.4%, respectively; OR, 0.64; 95% CI, 0.57-0.73). Based on the study results, the odds of having a week of well-controlled asthma were 14% higher in individuals treated in the budesonide-formoterol group compared with individuals in the terbutaline group. The rate of adherence was 78.9% in the budesonide maintenance group, and did not differ between twice-daily blinded maintenance regimen treatment groups.
The rate of severe exacerbations between groups was 0.20, 0.07, and 0.09 for terbutaline, budesonide-formoterol, and budesonide maintenance therapy, respectively. There was a 60% lower rate of severe exacerbations in individuals treated with budesonide-formoterol compared with individuals treated with terbutaline as needed (rate ratio [RR], 0.36; 95% CI, 0.27-0.49), as well as a 60% lower rate of moderate-to-severe exacerbations (0.14 vs 0.36). However, there was no difference in the rate of moderate-to-severe exacerbations between the budesonide-formoterol and budesonide maintenance group (RR, 95% CI, 0.74-1.21). Rate ratios were 0.36 for budesonide formoterol vs terbutaline and 0.83 for budesonide formoterol vs budesonide maintenance therapy (95% CI, 0.27-0.40 and 0.59-1.16, respectively).
Scores from the Asthma Control Questionnaire-5 favored the budesonide-formoterol group over the terbutaline group, and the budesonide maintenance group over the budesonide-formoterol group. There were more adverse events, including adverse events that led to therapy discontinuation, in the terbutaline group compared with the budesonide-formoterol and budesonide maintenance groups.
Researchers concluded that budesonide-formoterol was more effective than treatment with terbutaline used as needed for asthma symptom control. Although treatment with budesonide-formoterol was inferior to budesonide maintenance therapy in achieving weeks with well-controlled asthma, it eliminated the need for twice-daily maintenance therapy adherence, and was similar to budesonide maintenance therapy in reducing the risk for asthma exacerbations while using a significantly lower dose of glucocorticoid.
Disclosures: This study was funded by AstraZeneca.
O’Byrne PM, FitzGerald M, Bateman ED, et al. Inhaled combined budesonide-formoterol as needed in mild asthma. N Engl J Med. 2018;378(20):1865-1876.