Clinical Question

For patients with mild asthma, is as-needed use of an inhaled steroid/long-acting beta-agonist as effective as either as-needed albuterol alone or as-needed albuterol plus daily use of an inhaled steroid?

Bottom Line

In these patients with mild asthma (more than one-half used a short-acting beta-agonist [SABA] such as albuterol two or fewer times per week), as-needed use of a combined budesonide/formoterol (Symbicort) inhaler was as effective at preventing exacerbations as daily maintenance budesonide (Pulmicort) plus an as-needed SABA, and both were better than an as-needed SABA alone. The trial loses points for failing to mask outcome assessors and for having an imbalance in the number of previous severe exacerbations at baseline. (Level of Evidence = 1b–)

Synopsis

This study included patients with mild asthma who used a SABA alone at least twice in the previous three months, but no more than twice daily on average, and those who used a SABA alone and experienced a severe exacerbation in the past 12 months (7.3% of those enrolled). This raised the question of why a patient who had had a severe exacerbation (defined as requiring systemic corticosteroids or hospitalization) was being managed by a SABA alone. Patients hospitalized in the past 12 months were excluded. A total of 668 patients were randomized into one of three groups: (1) continued use of an as-needed SABA alone, (2) budesonide, 200 mcg twice daily, plus the SABA as needed, and (3) use of a combination inhaler containing 200 mcg of budesonide and 6 mcg of formoterol, one inhalation as needed to control symptoms. At baseline, there were some imbalances, with fewer women in the as-needed SABA group (50.7% vs. 55.5% to 57.3%), and more serious exacerbations in the past 12 months in the as-needed SABA group (20 vs. 17 for budesonide maintenance and only 12 for the budesonide/formoterol group). Analysis was by intention to treat, and only 13 patients were lost to follow-up during the one-year study. An exacerbation was defined as worsening symptoms requiring an urgent visit to a physician, prescription of a systemic corticosteroid, or heavy use of a SABA during a 24-hour period. The rate of exacerbations was significantly higher in the as-needed SABA group (0.4 per patient per year) compared with either budesonide/formoterol (0.195 per patient per year) or budesonide maintenance (0.175 per patient per year). For 100 patients there would be 40, 20, and 18 exacerbations per year, respectively (number needed to treat = 5 to prevent one exacerbation over one year). There were significantly fewer serious exacerbations in the as-needed budesonide/formoterol group than in the maintenance budesonide or as-needed SABA-only groups; nine, 21, and 23 episodes, respectively. The imbalance in severe exacerbations at baseline may have influenced this to some degree.

Study design: Randomized controlled trial (nonblinded)

Funding source: Industry

Allocation: Concealed

Setting: Outpatient (any)

Reference: Beasley R, Holliday M, Reddel HK, et al.; Novel START Study Team. Controlled trial of budesonide-formoterol as needed for mild asthma. N Engl J Med. 2019;380(21):2020–2030.

Editor's Note: Dr. Ebell is deputy editor for evidence-based medicine for AFP and cofounder and editor-in-chief of Essential Evidence Plus, published by Wiley-Blackwell.