| Design | Double-blind, multicentre, non-inferiority RCT |
|---|---|
| Treatment | As-needed budesonide 200 microg / formoterol 6 microg with twice-daily placebo |
| Control | Twice-daily budesonide 200 microg with as-needed terbutaline |
| Population | 4176 patients aged 12 and over with mild asthma eligible for regular inhaled steroids |
| Follow-up | 52 weeks |
| Primary endpoint | Annualised rate of severe exacerbations, non-inferiority limit 1.2 |
| Result | Severe exacerbations 0.11 per year (95% CI 0.10 to 0.13) with as-needed budesonide/formoterol versus 0.12 (0.10 to 0.14) with maintenance budesonide — rate ratio 0.97, upper one-sided 95% confidence limit 1.16, meeting non-inferiority. Median daily inhaled steroid dose 66 microg versus 267 microg. ACQ-5 favoured maintenance therapy by 0.11 units (0.07 to 0.15). |
| Secondary endpoints | Time to first exacerbation, ACQ-5 symptom score, inhaled glucocorticoid dose |
In patients with mild asthma, budesonide-formoterol used as needed was noninferior to twice-daily budesonide with respect to the rate of severe asthma exacerbations during 52 weeks of treatment but was inferior in controlling symptoms.
The trial authors, in the published abstract
The trial that made as-needed combination therapy defensible as a maintenance strategy rather than just a rescue one: same exacerbation protection, a quarter of the steroid. The symptom penalty is small but real, and is the honest caveat when counselling a patient who wants to feel well day to day. See also SYGMA 1.
Bateman ED, Reddel HK, O'Byrne PM, et al. As-Needed Budesonide-Formoterol versus Maintenance Budesonide in Mild Asthma. N Engl J Med 2018 May 17;378(20):1877-1887.