Budesonide/formoterol for maintenance and relief in uncontrolled asthma vs. high-dose salmeterol/fluticasone

Respir Med. 2007 Dec;101(12):2437-46. doi: 10.1016/j.rmed.2007.07.014. Epub 2007 Oct 1.

Abstract

Background: Budesonide/formoterol maintenance and reliever therapy (Symbicort SMART) improves asthma control compared with fixed-dose inhaled corticosteroid/long-acting beta(2)-agonist (ICS/LABA) regimens, but its efficacy has not been assessed in comparison with sustained high-dose salmeterol/fluticasone (Seretide) plus a short-acting beta(2)-agonist (SABA).

Methods: Patients (N=2309) with symptomatic asthma (aged 12 years; forced expiratory volume in 1s 50% predicted), who had experienced an asthma exacerbation in the previous year, were randomised to receive budesonide/formoterol 160/4.5 microg two inhalations twice daily and as needed, or one inhalation of salmeterol/fluticasone 50/500 microg twice daily plus terbutaline as needed, for 6 months.

Results: Time to first severe exacerbation, the pre-specified primary outcome, was not significantly prolonged (risk ratio 0.82; 95% confidence interval 0.63, 1.05). Budesonide/formoterol maintenance and reliever therapy reduced total exacerbations from 31 to 25 events/100 patients/year (P=0.039), and exacerbations requiring hospitalisation/emergency room (ER) treatment from 13 to 9 events/100 patients/year (P=0.046). The treatments showed no difference in measures of lung function or asthma symptoms. The mean dose of ICS received was lower using budesonide/formoterol maintenance and reliever therapy (792 microg/day budesonide [1238 microg/day beclomethasone dipropionate (BDP) equivalent] versus 1000 microg/day fluticasone [2000 microg/day BDP equivalent] with salmeterol/fluticasone therapy; P<0.0001). Both treatments were well tolerated.

Conclusion: In the treatment of uncontrolled asthma, budesonide/formoterol maintenance and reliever therapy reduces the incidence of severe asthma exacerbations and hospitalisation/ER treatment with similar daily symptom control compared with sustained high-dose salmeterol/fluticasone plus SABA. This benefit is achieved with substantially less ICS exposure.

Trial registration: ClinicalTrials.gov NCT00242775.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adolescent
  • Adrenergic beta-Agonists / therapeutic use
  • Adult
  • Aged
  • Aged, 80 and over
  • Albuterol / analogs & derivatives*
  • Albuterol / therapeutic use
  • Androstadienes / therapeutic use*
  • Anti-Asthmatic Agents / therapeutic use*
  • Asthma / drug therapy*
  • Asthma / physiopathology
  • Azides / therapeutic use
  • Budesonide / therapeutic use*
  • Child
  • Chronic Disease
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Combinations
  • Drug Therapy, Combination
  • Ethanolamines / therapeutic use*
  • Female
  • Fluticasone-Salmeterol Drug Combination
  • Formoterol Fumarate
  • Hospitalization
  • Humans
  • Lung / physiopathology
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Respiratory Function Tests
  • Serotonin / analogs & derivatives
  • Serotonin / therapeutic use
  • Treatment Outcome

Substances

  • Adrenergic beta-Agonists
  • Androstadienes
  • Anti-Asthmatic Agents
  • Azides
  • Drug Combinations
  • Ethanolamines
  • Fluticasone-Salmeterol Drug Combination
  • Serotonin
  • Budesonide
  • 3-(2-(4-azidobenzamidino)ethyl)-5-hydroxyindole
  • Albuterol
  • Formoterol Fumarate

Associated data

  • ClinicalTrials.gov/NCT00242775