title: Safety of formoterol in adults and children with asthma: a meta-analysis.
abstract: BACKGROUND
  The safety of long-acting β2 agonists (LABA) for the treatment of persistent asthma remains a topic of ongoing debate.
  
  
  OBJECTIVE
  To evaluate the risk of serious asthma-related events among patients treated with formoterol, a meta-analysis of all Novartis-sponsored controlled clinical trials was conducted.
  
  
  METHODS
  Forty-five randomized, placebo- and active-controlled, parallel-group or crossover studies with formoterol were included. Background inhaled corticosteroid (ICS) use was permitted in all studies; however, in only 2 studies was ICS randomized as study medication. Sub-analyses of the pooled data were performed according to age (5-12; 13-18; >18 years), baseline ICS use, and lung function. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated between formoterol (twice-daily), albuterol (salbutamol) 4 times per day (active control), and placebo.
  
  
  RESULTS
  Patients were randomized to formoterol (n = 5,367), placebo (n = 2,026), and albuterol (n = 976). Two deaths were reported, 1 each in the formoterol (asthma exacerbation) and the placebo (hemorrhagic pancreatitis) groups. No statistically significant differences in serious asthma exacerbations were observed compared with placebo in adolescents and adults. In children, a higher frequency of hospitalizations was observed among patients treated with formoterol compared with placebo (OR 8.4; 95% CI: 1.1-65.3). A trend toward fewer exacerbations was observed among subjects reporting concomitant ICS use at baseline.
  
  
  CONCLUSIONS
  This analysis supports current guideline recommendations for the use of LABAs only as add-on therapy to ICS.
authors.affiliation: School of Medicine, University of California-San Diego, CA, USA.
authors.forename: James
authors.initials: J
authors.lastname: Kemp
authors.forename: Linda
authors.initials: L
authors.lastname: Armstrong
authors.forename: Ying
authors.initials: Y
authors.lastname: Wan
authors.forename: Vijay Kumar Thygarajan
authors.initials: VK
authors.lastname: Alagappan
authors.forename: David
authors.initials: D
authors.lastname: Ohlssen
authors.forename: Steve
authors.initials: S
authors.lastname: Pascoe
mesh_terms: D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000009:adverse effects / Q000627:therapeutic use; D000328:Adult; D000420:Albuterol / Q000009:adverse effects / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy*; D001993:Bronchodilator Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D004359:Drug Therapy, Combination / Q000009:adverse effects; D004983:Ethanolamines / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D000068759:Formoterol Fumarate; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D017410:Practice Guidelines as Topic; D016032:Randomized Controlled Trials as Topic; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones; D001993:Bronchodilator Agents; D004983:Ethanolamines; D000420:Albuterol; D000068759:Formoterol Fumarate