Safety of budesonide/formoterol maintenance and reliever therapy in asthma trials

• Published in: Respiratory medicine Vol. 103; no. 12; pp. 1960 - 1968
• Main Authors: Sears, Malcolm R, Radner, Finn
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01.12.2009; Elsevier; Elsevier Limited
• Subjects: Administration, Inhalation; Adolescent; Adult; Aged; Aged, 80 and over; Asthma; Asthma - drug therapy; Asthma - mortality; Biological and medical sciences; Bronchodilator Agents - administration & dosage; Bronchodilator Agents - adverse effects; Budesonide - administration & dosage; Budesonide - adverse effects; Budesonide/formoterol maintenance and reliever therapy; Child; Chronic obstructive pulmonary disease, asthma; Clinical trials; Confidence intervals; Drug Combinations; Drug Therapy, Combination; Epidemiologic Methods; Ethanolamines - administration & dosage; Ethanolamines - adverse effects; Fatalities; Female; Formoterol Fumarate; Humans; Male; Medical sciences; Middle Aged; Mortality; Pneumology; Powders - administration & dosage; Powders - adverse effects; Pulmonary/Respiratory; Safety; Serious adverse events; Young Adult; Safety; Budesonide/formoterol maintenance and reliever therapy; Asthma; Serious adverse events; Lung disease; Budesonide; Respiratory disease; Maintenance; Treatment; Bronchus disease; Formoterol; Obstructive pulmonary disease; Pneumology
• ISSN: 0954-6111; 1532-3064
• DOI: 10.1016/j.rmed.2009.08.007

Summary Background The safety of long-acting β2 -agonists (LABAs) in asthma is debated. This study examined the safety of the inhaled corticosteroid (ICS)/LABA combination budesonide/formoterol dry powder inhaler used as maintenance and reliever therapy versus combination treatments based on guideline recommendations. Methods Safety data from six double-blind, randomised clinical trials (RCTs) in asthma where budesonide/formoterol was used as maintenance and reliever therapy for at least 6 months were reviewed ( N = 14 346). All-cause mortality and asthma-related serious adverse events (SAEs) (co-primary endpoints), overall and cardiac SAEs, and discontinuations due to adverse events (DAEs) were assessed. Estimated Mantel–Haenszel (MH) relative risks (RR) with this regimen versus comparators were calculated. Results There was no increase in all-cause mortality with budesonide/formoterol maintenance and reliever therapy (four deaths [0.07%] versus nine [0.10%]; pooled MH RR 0.70, 95% confidence interval [CI] 0.21–2.30). Asthma-related SAEs were reduced with budesonide/formoterol maintenance and reliever therapy: 41 (0.73%) versus 121 (1.38%); pooled MH RR 0.59, 95% CI 0.42–0.85. All-cause and asthma-related DAEs were also reduced with budesonide/formoterol maintenance and reliever therapy: pooled MH RR 0.60 (95% CI 0.46–0.79) and 0.43 (0.28–0.68), respectively. Overall and cardiac-related SAEs were comparable between treatment groups: pooled MH RR 0.96 (95% CI 0.82–1.14) and 1.26 (0.72–2.22), respectively. Conclusion Budesonide/formoterol dry powder inhaler maintenance and reliever therapy was well tolerated in RCTs versus fixed-dose alternatives and not associated with increased risk of death or cardiac-related SAEs and DAEs, and asthma-related SAEs and DAEs were significantly reduced. Given the limitations of RCTs, particularly exclusion of patients with co-morbidities, ongoing surveillance is appropriate.