Age and risks of FDA-approved long-acting β₂-adrenergic receptor agonists.
OBJECTIVE
To determine the risk, by age group, of serious asthma-related events with long-acting β(2)-adrenergic receptor agonists marketed in the United States for asthma.


METHODS
The US Food and Drug Administration performed a meta-analysis of controlled clinical trials comparing the risk of LABA use with no LABA use for patients 4 to 11, 12 to 17, 18 to 64, and older than 64 years old. The effects of age on a composite of asthma-related deaths, intubations, and hospitalizations (asthma composite index) and the effects of concomitant inhaled corticosteroid (ICS) use were analyzed.


RESULTS
One hundred ten trials with 60 954 patients were included in the meta-analysis. The composite event incidence difference for all ages was 6.3 events per 1000 patient-years (95% confidence interval [CI]: 2.2-10.3) for using LABAs compared with not using LABAs. The largest incidence difference was observed for the 4- to 11-year age group (30.4 events per 1000 patient-years [95% CI: 5.7-55.1]). Differences according to age were statistically significant (P = .020). Results for the subgroup of patients with concomitant ICS use (n = 36 210) were similar to the overall results; with assigned ICSs (n = 15 192), the incidence difference was 0.4 events per 1000 patient-years (95% CI: -3.8 to 4.6), and there was no statistically significant difference according to age group.


CONCLUSIONS
The excess of serious asthma-related events attributable to LABAs was greatest among children. Additional data are needed to assess risks of LABA use for children with simultaneous ICS use.
Office of Pediatric Therapeutics, Office of the Commissioner, Food and Drug Administration, Silver Spring, MD 20993, USA. ann.mcmahon@fda.hhs.gov
Ann W
AW
McMahon
Mark S
MS
Levenson
Bradley W
BW
McEvoy
Andrew D
AD
Mosholder
Dianne
D
Murphy
D000293:Adolescent; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage / Q000009:adverse effects*; D000367:Age Factors; D000368:Aged; D018927:Anti-Asthmatic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001249:Asthma / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality*; D002423:Cause of Death; D002648:Child; D002675:Child, Preschool; D003692:Delayed-Action Preparations / Q000009:adverse effects* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D017277:Drug Approval; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D016019:Survival Analysis; D014481:United States; D014486:United States Food and Drug Administration
D058666:Adrenergic beta-2 Receptor Agonists; D018927:Anti-Asthmatic Agents; D003692:Delayed-Action Preparations