Safety of formoterol in patients with asthma: combined analysis of data from double-blind, randomized controlled trials.
BACKGROUND
Concerns exist that regular long-acting beta(2)-adrenergic agonist (LABA) therapy may increase the risk of serious asthma-related events.


OBJECTIVE
To assess risks of formoterol-containing versus non-LABA treatment by using a large asthma database.


METHODS
This analysis included all blind, parallel-arm, randomized, active-controlled and/or placebo-controlled AstraZeneca-sponsored asthma studies with formoterol-containing and non-LABA comparator arms. Serious adverse events were assessed for inclusion in all-cause death, asthma-related death, asthma-related intubation, and asthma-related hospitalization categories by using blind adjudication. Data were combined across trials; relative risk (RR) was assessed by using Mantel-Haenszel methods.


RESULTS
Data were from 13,542 formoterol-randomized and 9968 non-LABA patients 4 years or older (42 trials), of whom 93% and 89%, respectively, received inhaled corticosteroid as part of randomized treatment or allowed medication. Incidence of all-cause death was low (n=3 and n=4, respectively), with numerically lower all-cause deaths/1000 patient-treatment years in the formoterol-treated group (0.53) versus the non-LABA group (0.82) (RR, 0.64; 95% confidence interval [CI], 0.14-2.92). No asthma-related deaths and 1 asthma-related intubation (formoterol-treated group) occurred. Asthma-related hospitalizations/1000 patient-treatment years were lower numerically in the formoterol-treated group (12.1) versus the non-LABA group (16.4) (RR, 0.73; 95% CI, 0.54-1.01), with fewer study discontinuations in the formoterol-treated group (12.7% vs 15.4%, respectively; RR, 0.79; 95% CI, 0.74-0.85). Relative to non-LABA, increasing daily formoterol dose (>/=4.5, 9, 18, 36 mug) did not increase the rate or incidence of asthma-related hospitalization.


CONCLUSIONS
No evidence of increased risk of asthma-related hospitalization, no asthma-related deaths, and a low incidence of all-cause death and asthma-related intubation were seen with formoterol-containing versus non-LABA treatment.
Nelson
Harold
H
National Jewish Health, Denver, CO80206, USA. nelsonh@njhealth.org
Bonuccelli
Catherine
C
Radner
Finn
F
Ottosson
Anders
A
Carroll
Kevin J
KJ
Andersson
Tomas L G
TL
LaForce
Craig
C
D018927:Anti-Asthmatic Agents / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy*; D001993:Bronchodilator Agents / Q000009:adverse effects*; D004311:Double-Blind Method; D004983:Ethanolamines / Q000009:adverse effects*; D000068759:Formoterol Fumarate; D006801:Humans; D016032:Randomized Controlled Trials as Topic
D018927:Anti-Asthmatic Agents; D001993:Bronchodilator Agents; D004983:Ethanolamines; D000068759:Formoterol Fumarate