title: Budesonide/formoterol maintenance and reliever therapy via Turbuhaler versus fixed-dose budesonide/formoterol plus terbutaline in patients with asthma: phase III study results.
abstract: OBJECTIVE
  To evaluate the efficacy and tolerability of budesonide/formoterol as maintenance and reliever therapy versus budesonide/formoterol maintenance plus terbutaline in adults with persistent asthma not adequately controlled with inhaled corticosteroid (ICS) therapy alone.
  
  
  METHODS
  In this 12-month, randomized, double-blind, parallel-group, phase III study (NCT00839800), patients (age ≥ 16 years; receiving maintenance ICS; ≥ 1 severe exacerbation in the 12 months prior to study entry) were randomized to either budesonide/formoterol 160/4.5 μg 1 inhalation twice daily plus budesonide/formoterol 160/4.5 μg as-needed or budesonide/formoterol 160/4.5 μg 1 inhalation twice daily plus terbutaline 0.4 mg as-needed for 12 months.
  
  
  METHODS
  time to first severe asthma exacerbation; secondary outcomes included: lung function, asthma symptom variables and tolerability.
  
  
  RESULTS
  Two thousand and ninety-one patients were randomized: 170 (16%) receiving budesonide/formoterol maintenance and reliever therapy experienced 259 severe exacerbations versus 229 patients (22%) receiving budesonide/formoterol plus terbutaline who experienced 363 severe exacerbations. Budesonide/formoterol maintenance and reliever therapy prolonged the time to first severe exacerbation versus budesonide/formoterol plus terbutaline (P = 0.0007) and reduced the instantaneous risk of an exacerbation by 30% (hazard ratio 0.70, 95% confidence interval 0.57-0.85, P = 0.0003). Times to first oral steroid use, first hospitalization and first emergency room treatment were all significantly prolonged in the budesonide/formoterol maintenance and reliever group versus budesonide/formoterol plus terbutaline. Both treatment groups were well tolerated.
  
  
  CONCLUSIONS
  Budesonide/formoterol maintenance and reliever therapy provided more effective asthma control, including a prolonged time to first severe asthma exacerbation, than budesonide/formoterol plus terbutaline and was well tolerated. Budesonide/formoterol maintenance and reliever therapy also improved lung function and asthma symptoms.
authors.affiliation: Mary Mediatrix Medical Center, Lipa City, Batangas, Philippines. drtito104@yahoo.com
authors.forename: Tito
authors.initials: T
authors.lastname: Atienza
authors.forename: Teresita
authors.initials: T
authors.lastname: Aquino
authors.forename: Marcelo
authors.initials: M
authors.lastname: Fernández
authors.forename: Watchara
authors.initials: W
authors.lastname: Boonsawat
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Kawai
authors.forename: Takahide
authors.initials: T
authors.lastname: Kudo
authors.forename: Jan
authors.initials: J
authors.lastname: Ekelund
authors.forename: Stefan
authors.initials: S
authors.lastname: Ivanov
authors.forename: Lars-Goran
authors.initials: LG
authors.lastname: Carlsson
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000627:therapeutic use; D000328:Adult; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D019819:Budesonide / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004983:Ethanolamines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects / Q000502:physiology; D000068759:Formoterol Fumarate; D006801:Humans; D008137:Longitudinal Studies; D008168:Lung / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D013726:Terbutaline / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D001993:Bronchodilator Agents; D004983:Ethanolamines; D019819:Budesonide; D013726:Terbutaline; D000068759:Formoterol Fumarate