| Design | Double-blind RCT, three arms |
|---|---|
| Treatment | As-needed budesonide 200 microg / formoterol 6 microg, with twice-daily placebo |
| Control | As-needed terbutaline 0.5 mg with twice-daily placebo, or twice-daily budesonide 200 microg with as-needed terbutaline |
| Population | 3836 patients aged 12 and over with mild asthma |
| Follow-up | 52 weeks |
| Primary endpoint | Electronically recorded weeks with well-controlled asthma |
| Result | Well-controlled weeks 34.4% with as-needed budesonide/formoterol versus 31.1% with terbutaline (odds ratio 1.14, 95% CI 1.00 to 1.30, p=0.046) but 44.4% with maintenance budesonide (odds ratio 0.64, 0.57 to 0.73). Severe exacerbations 0.07 per year with budesonide/formoterol, 0.09 with maintenance budesonide and 0.20 with terbutaline (rate ratio 0.36, 0.27 to 0.49 versus terbutaline). |
| Secondary endpoints | Severe exacerbation rate, inhaled glucocorticoid exposure |
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.
The trial authors, in the published abstract
Together with SYGMA 2 this ended short-acting beta agonist monotherapy in mild asthma, and the pair now underpin the GINA recommendation that every asthmatic receives an inhaled steroid whenever they use a reliever. Note what it does not show: for pure symptom control, daily budesonide still wins.
O'Byrne PM, FitzGerald JM, Bateman ED, et al. Inhaled Combined Budesonide-Formoterol as Needed in Mild Asthma. N Engl J Med 2018 May 17;378(20):1865-1876.