PURPOSE OF THE STUDY.
This meta-analysis investigated the relationship between adverse asthma-related events and long-acting β2-adrenergic receptor antagonists (LABAs) among different age groups. Previous studies have suggested a correlation between increased risk and LABA use that seems most pronounced among children.
The meta-analysis included 110 trials with 60 954 patients, 9807 of whom were children between the ages of 4 and 18 years. All trials included were randomized controlled trials of LABAs for the treatment of asthma. Only Food and Drug Administration (FDA)-approved LABA products and doses were included.
The FDA-identified controlled trials comparing the risks of LABA to no LABA use in subjects by age group: 4 to 11, 12 to 17, 18 to 64, and >64 years. The primary composite end point was asthma-related death, intubation, or hospitalization. Subgroup analysis included patients with use of any amount of concomitant inhaled corticosteroid (ICS) and those assigned to regular ICS use.
The composite event incidence difference for the LABA group compared with the non-LABA group was 6.3 events per 1000 patient-years (95% confidence interval: 2.2–10.3). A correlation was observed between decreasing age and increasing incidence difference (P = .020), with the greatest incidence difference occurring in the youngest age group of 4 to 11 years (30.4 events per 1000 patient-years [95% confidence interval: 5.7–55.1]). The overall incidence difference and age trend were similar in the subgroup using any amount of concomitant ICS; however, among those assigned regular ICS use, there was neither an age trend nor a statistically significant increase in events with LABA use, except in patients >64 years.
The results of this meta-analysis suggest a higher incidence of asthma events associated with LABA use and show a trend between decreasing age and increased LABA risk; however, this increased risk among LABA users was not observed in a subgroup also prescribed regular ICS. Because of the small numbers of pediatric patients in this subgroup, the authors recommend further investigation into the risks of LABAs with concomitant ICS.
This meta-analysis adds to the growing body of literature suggesting increased risk with LABAs used alone that appears to be mitigated or abolished by concomitant regular use of ICS. The results also substantiate a trend of increasing LABA risk with decreasing age among pediatric patients. As the authors highlight, the small sample size of the subgroup of pediatric patients using concomitant regular ICS leaves room for further study. Both the FDA and National Asthma Education and Prevention Program currently advise against LABAs as monotherapy for asthma in any age group.
- Copyright © 2012 by the American Academy of Pediatrics