Clinical Question

Is adding a long-acting beta-agonist (LABA) to an inhaled corticosteroid safe and effective for patients with persistent asthma?

Bottom Line

Adding a LABA to an inhaled corticosteroid is safe but does not reduce the likelihood of a serious exacerbation requiring hospitalization. There is a small reduction in nonsevere asthma exacerbations, with one fewer exacerbation for every 53 patients treated for six months. (Level of Evidence = 1b)

Synopsis

The use of a LABA as the sole medication to control asthma was associated with increased mortality. The U.S. Food and Drug Administration mandated that companies that make a LABA do adequately powered randomized trials to assess the safety and efficacy of adding a LABA or placebo to an inhaled corticosteroid in patients with persistent asthma. This current study is a pre-planned combined analysis of these four 26-week drug company–sponsored trials. Each study used a different LABA, but the results were consistent across trials. There were only two asthma-related deaths (both in the inhaled corticosteroid–LABA group) and three intubations (two in the inhaled corticosteroid group, one in the inhaled corticosteroid–LABA group). In the combined analysis, there was no significant difference in the risk of hospitalization between groups (0.60% for inhaled corticosteroid vs. 0.66% for inhaled corticosteroid–LABA). The likelihood of an asthma exacerbation was lower in the inhaled corticosteroid–LABA group (9.8% vs. 11.7%; P < .001; number needed to treat = 53).

Study design: Randomized controlled trial (double-blinded)

Funding source: Industry

Allocation: Concealed

Setting: Outpatient (any)

Reference: Busse WW, Bateman ED, Caplan AL, et al. Combined analysis of asthma safety trials of long-acting β2-agonists. N Engl J Med. 2018;378(26):2497–2505.

Editor's Note: Dr. Mark H. Ebell is Deputy Editor for Evidence-Based Medicine in AFP and cofounder and Editor-in-Chief of Essential Evidence Plus, published by Wiley-Blackwell, Inc.