Controlled Trial of Budesonide-Formoterol as Needed for Mild Asthma.

BACKGROUND In double-blind, placebo-controlled trials, budesonide-formoterol used on an as-needed basis resulted in a lower risk of severe exacerbation of asthma than as-needed use of a short-acting β2-agonist (SABA); the risk was similar to that of budesonide maintenance therapy plus as-needed SABA. The availability of data from clinical trials designed to better reflect clinical practice would be beneficial. METHODS We conducted a 52-week, randomized, open-label, parallel-group, controlled trial involving adults with mild asthma. Patients were randomly assigned to one of three treatment groups: albuterol (100 μg, two inhalations from a pressurized metered-dose inhaler as needed for asthma symptoms) (albuterol group); budesonide (200 μg, one inhalation through a Turbuhaler twice daily) plus as-needed albuterol (budesonide maintenance group); or budesonide-formoterol (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 annualized rate of asthma exacerbations. RESULTS The analysis included 668 of 675 patients who underwent randomization. The annualized exacerbation rate in the budesonide-formoterol group was lower than that in the albuterol group (absolute rate, 0.195 vs. 0.400; relative rate, 0.49; 95% confidence interval [CI], 0.33 to 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 to 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 to 0.86) and the budesonide maintenance group (9 vs. 21; relative risk, 0.44; 95% CI, 0.20 to 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. CONCLUSIONS In an open-label trial involving adults with mild asthma, budesonide-formoterol used as needed was superior to albuterol used as needed for the prevention of asthma exacerbations. (Funded by AstraZeneca and the Health Research Council of New Zealand; Novel START Australian New Zealand Clinical Trials Registry number, ACTRN12615000999538.).

[1]  A. Goldsobel.  Association of Inhaled Corticosteroids and Long-Acting β-Agonists as Controller and Quick Relief Therapy With Exacerbations and Symptom Control in Persistent Asthma: A Systematic Review and Meta-analysis , 2018, Pediatrics.

[2]  M. Weatherall,et al.  The further paradoxes of asthma management: time for a new approach across the spectrum of asthma severity , 2018, European Respiratory Journal.

[3]  E. Bateman,et al.  As‐Needed Budesonide–Formoterol versus Maintenance Budesonide in Mild Asthma , 2018, The New England journal of medicine.

[4]  E. Bateman,et al.  Inhaled Combined Budesonide–Formoterol as Needed in Mild Asthma , 2018, The New England journal of medicine.

[5]  I. Pavord,et al.  Quadrupling Inhaled Glucocorticoid Dose to Abort Asthma Exacerbations , 2018, The New England journal of medicine.

[6]  C. Jenkins,et al.  The paradoxes of asthma management: time for a new approach? , 2017, European Respiratory Journal.

[7]  W. Busse,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 , 2017, The Lancet.

[8]  R. Hancox,et al.  Asthma and Respiratory Foundation NZ adult asthma guidelines: a quick reference guide. , 2016, The New Zealand medical journal.

[9]  Richard Beasley,et al.  Validation of a metered dose inhaler electronic monitoring device: implications for asthma clinical trial use , 2016, BMJ Open Respiratory Research.

[10]  I. Pavord,et al.  Description of a randomised controlled trial of inhaled corticosteroid/fast-onset LABA reliever therapy in mild asthma , 2016, European Respiratory Journal.

[11]  M. Weatherall,et al.  Three-month validation of a turbuhaler electronic monitoring device: implications for asthma clinical trial use , 2015, BMJ Open Respiratory Research.

[12]  D. Shaw,et al.  Efficacy and safety of maintenance and reliever combination budesonide-formoterol inhaler in patients with asthma at risk of severe exacerbations: a randomised controlled trial. , 2013, The Lancet. Respiratory medicine.

[13]  Martyn R Partridge,et al.  British Guideline on the Management of Asthma , 2008, Thorax.

[14]  C. Delacourt,et al.  Mild asthma: an expert review on epidemiology, clinical characteristics and treatment recommendations , 2007, Allergy.

[15]  G. Canonica,et al.  Rescue use of beclomethasone and albuterol in a single inhaler for mild asthma. , 2007, The New England journal of medicine.

[16]  G. Rodrigo.  Rapid effects of inhaled corticosteroids in acute asthma: an evidence-based evaluation. , 2006, Chest.

[17]  P. Thompson,et al.  Formoterol Turbuhaler as reliever medication in patients with acute asthma , 2006, European Respiratory Journal.

[18]  P-C. Yang,et al.  Efficacy and safety of budesonide/formoterol compared with salbutamol in the treatment of acute asthma. , 2006, Pulmonary pharmacology & therapeutics.

[19]  Klas Svensson,et al.  Measurement properties and interpretation of three shortened versions of the asthma control questionnaire. , 2005, Respiratory medicine.

[20]  M. Bala,et al.  Inhaled corticosteroids for asthma therapy: patient compliance, devices, and inhalation technique. , 2000, Chest.

[21]  R. Hancox,et al.  Combination corticosteroid/β-agonist inhaler as reliever therapy: a solution for intermittent and mild asthma? , 2014, The Journal of allergy and clinical immunology.

[22]  I. Pavord,et al.  An official American Thoracic Society/European Respiratory Society statement: asthma control and exacerbations: standardizing endpoints for clinical asthma trials and clinical practice. , 2009, American journal of respiratory and critical care medicine.

[23]  C. Camargo,et al.  Early use of inhaled corticosteroids in the emergency department treatment of acute asthma. , 2000, The Cochrane database of systematic reviews.