Highlights from

ATS 2019

American Thoracic Society international conference

Dallas, USA 17-22 May 2019

Budesonide-Formoterol Combination Superior to Albuterol in Prevention Asthma Exacerbation

Research shows that a combination drug of budesonide-formoterol is superior to the treatment of a single medication of albuterol on an as-needed basis for the prevention of asthma exacerbations in adults with mild asthma [1].

The risk of exacerbations in mild asthma is reduced by inhaled glucocorticoid therapy as a maintenance treatment [2]. Yet, the therapy is not often recommended as patients seem reluctant to use the inhaler when their symptoms are mild and infrequent [3]. An alternative treatment is the use of an inhaler combining glucocorticoid and a fast-onset β2-agonist on an as-needed basis as reliever therapy [4-6]. Two recent randomized, double-blind, placebo-controlled trials showed the efficacy and safety of budesonide–formoterol as reliever therapy in patients with mild asthma [7,8]. Although these studies have high internal validity, their generalisability is limited. It is unclear to what extent the findings translate to clinical practice. Therefore, an open-label clinical trial was designed with a focus on overcoming the previous study’s limitations.

Prof. Richard Beasley (University of Otago, New Zealand) and his team conducted a 52-week, randomised, open-label, parallel-group, controlled trial involving adults with mild asthma. Patients (n=668) were randomly assigned to 3 treatment groups: albuterol group (100 μg, two inhalations from a pressurised metered-dose inhaler as needed for asthma symptoms); budesonide maintenance group (200 μg, one inhalation through a Turbuhaler twice daily) plus as-needed albuterol; or budesonide-formoterol group (200 μg of budesonide and 6 μg of formoterol, one inhalation through a Turbuhaler as needed) (budesonide–formoterol group). Electronic monitoring of inhalers was used to measure medication use. The primary outcome was the annualised rate of asthma exacerbations. The mean (±SD) dose of inhaled budesonide was 107±109 μg per day in the budesonide-formoterol group and 222±113 μg per day in the budesonide maintenance group. The incidence and type of adverse events reported were consistent with those in previous trials and with reports in clinical use.

The annualized exacerbation rate in the budesonide-formoterol group was lower than that in the albuterol group (absolute rate 0.195 vs 0.400, respectively; relative rate 0.49; 95% CI, 0.33-0.72; P<0.001) and did not differ significantly from the rate in the budesonide maintenance group (absolute rate 0.195 in the budesonide-formoterol group vs 0.175 in the budesonide maintenance group; relative rate 1.12; 95% CI, 0.70- 1.79; P=0.65). The number of severe exacerbations was lower in the budesonide-formoterol group than in both the albuterol group (9 vs 23; relative risk 0.40; 95% CI, 0.18-0.86) and the budesonide maintenance group (9 vs 21; relative risk 0.44; 95% CI, 0.20- 0.96). The mean (±SD) dose of inhaled budesonide was 107±109 μg per day in the budesonide-formoterol group and 222±113 μg per day in the budesonide maintenance group. The incidence and type of adverse events reported were consistent with those in previous trials and with reports in clinical use.

Based on these findings the authors conclude that in patients with mild asthma budesonide-formoterol used as needed is superior to albuterol used as needed for the prevention of asthma exacerbations.

  1. Beasley R. et al. Controlled Trial of Budesonide–Formoterol as Needed for Mild Asthma. N Engl J Med 2019; May 19. DOI: 10.1056/NEJMoa1901963.
  2. Reddel HK, et al. Should recommendations about starting inhaled corticosteroid treatment for mild asthma be based on symptom frequency: a post-hoc efficacy analysis of the START study. Lancet 2017; 389: 157-66.
  3. Cochrane MG, Bala MV, Downs KE, Mauskopf J, Ben-Joseph RH. Inhaled corticosteroids for asthma therapy: patient compliance, devices, and inhalation technique. Chest 2000; 117: 542-50.
  4. Beasley R, Weatherall M, Shirtcliffe P, Hancox R, Reddel HK. Combination corticosteroid/β-agonist inhaler as reliever therapy: a solution for intermittent and mild asthma? J Allergy Clin Immunol 2014; 133: 39-41.
  5. O’Byrne PM, Jenkins C, Bateman ED. The paradoxes of asthma management: time for a new approach? Eur Respir J 2017; 50(3): 1701103.
  6. Beasley R, Bird G, Harper J, Weatherall M. The further paradoxes of asthma management: time for a new approach across the spectrum of asthma severity. Eur Respir J 2018; 52(5): 1800694.
  7. O’Byrne PM, FitzGerald JM, Bateman ED, et al. Inhaled combined budesonideformoterol as needed in mild asthma. N Engl J Med 2018; 378: 1865-76.
  8. Bateman ED, Reddel HK, O’Byrne PM, et al. As-needed budesonide-formoterol versus maintenance budesonide in mild asthma. N Engl J Med 2018; 378: 1877-87.

The content and interpretation of these conference highlights are the views and comments of the speakers/authors.