Safety of formoterol in patients with asthma: Combined analysis of data from double-blind, randomized controlled trials

• Published in: Journal of allergy and clinical immunology 2010-02, Vol.125 (2), p.390-396.e8
• Main Authors: Nelson, Harold, MD, Bonuccelli, Catherine, MD, Radner, Finn, PhD, Ottosson, Anders, MD, PhD, Carroll, Kevin J., MSc, BSc, Andersson, Tomas L.G., MD, PhD, LaForce, Craig, MD
• Format: Article
• Language: English
• Subjects: Allergy and Immunology; Anti-Asthmatic Agents - therapeutic use; Asthma; Asthma - drug therapy; Biological and medical sciences; Bronchodilator Agents - adverse effects; Chronic obstructive pulmonary disease, asthma; Confidence intervals; Double-Blind Method; Drug dosages; Drug therapy; Ethanolamines - adverse effects; formoterol; Formoterol Fumarate; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Hospitalization; Humans; Immunopathology; inhaled corticosteroid; Intubation; long-acting β 2-adrenergic agonist; Medical sciences; Methods; Pneumology; Randomized Controlled Trials as Topic; safety; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; serious adverse events; Studies
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2009.11.036

Background Concerns exist that regular long-acting β2 -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 μg) did not increase the rate or incidence of asthma-related hospitalization. Conclusion 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.