title: Safety of budesonide/formoterol maintenance and reliever therapy in asthma trials.
abstract: BACKGROUND
  The safety of long-acting beta(2)-agonists (LABAs) in asthma is debated. This study examined the safety of the inhaled corticosteroid (ICS)/LABA combination budesonide/formoterol dry powder inhaler used as maintenance and reliever therapy versus combination treatments based on guideline recommendations.
  
  
  METHODS
  Safety data from six double-blind, randomised clinical trials (RCTs) in asthma where budesonide/formoterol was used as maintenance and reliever therapy for at least 6 months were reviewed (N=14 346). All-cause mortality and asthma-related serious adverse events (SAEs) (co-primary endpoints), overall and cardiac SAEs, and discontinuations due to adverse events (DAEs) were assessed. Estimated Mantel-Haenszel (MH) relative risks (RR) with this regimen versus comparators were calculated.
  
  
  RESULTS
  There was no increase in all-cause mortality with budesonide/formoterol maintenance and reliever therapy (four deaths [0.07%] versus nine [0.10%]; pooled MH RR 0.70, 95% confidence interval [CI] 0.21-2.30). Asthma-related SAEs were reduced with budesonide/formoterol maintenance and reliever therapy: 41 (0.73%) versus 121 (1.38%); pooled MH RR 0.59, 95% CI 0.42-0.85. All-cause and asthma-related DAEs were also reduced with budesonide/formoterol maintenance and reliever therapy: pooled MH RR 0.60 (95% CI 0.46-0.79) and 0.43 (0.28-0.68), respectively. Overall and cardiac-related SAEs were comparable between treatment groups: pooled MH RR 0.96 (95% CI 0.82-1.14) and 1.26 (0.72-2.22), respectively.
  
  
  CONCLUSIONS
  Budesonide/formoterol dry powder inhaler maintenance and reliever therapy was well tolerated in RCTs versus fixed-dose alternatives and not associated with increased risk of death or cardiac-related SAEs and DAEs, and asthma-related SAEs and DAEs were significantly reduced. Given the limitations of RCTs, particularly exclusion of patients with co-morbidities, ongoing surveillance is appropriate.
authors.affiliation: Firestone Institute for Respiratory Health, St Joseph's Healthcare and McMaster University, 50 Charlton Ave East, Hamilton, Ontario, Canada L8N 4A6. searsm@mcmaster.ca
authors.forename: Malcolm R
authors.initials: MR
authors.lastname: Sears
authors.forename: Finn
authors.initials: F
authors.lastname: Radner
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001249:Asthma / Q000188:drug therapy* / Q000401:mortality; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000009:adverse effects*; D019819:Budesonide / Q000008:administration & dosage / Q000009:adverse effects*; D002648:Child; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D004812:Epidemiologic Methods; D004983:Ethanolamines / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D000068759:Formoterol Fumarate; D006801:Humans; D008297:Male; D008875:Middle Aged; D011208:Powders / Q000008:administration & dosage / Q000009:adverse effects; D055815:Young Adult
chemical_list: D001993:Bronchodilator Agents; D004338:Drug Combinations; D004983:Ethanolamines; D011208:Powders; D019819:Budesonide; D000068759:Formoterol Fumarate