Effect of budesonide/formoterol pMDI on COPD exacerbations: A double-blind, randomized study

• Published in: Respiratory medicine 2012-02, Vol.106 (2), p.257-268
• Main Authors: Sharafkhaneh, Amir, Southard, John G, Goldman, Mitchell, Uryniak, Tom, Martin, Ubaldo J
• Format: Article
• Language: English
• Subjects: Administration, Inhalation; Adult; Aged; Aged, 80 and over; Biological and medical sciences; Bronchodilator Agents - administration & dosage; Bronchodilator Agents - therapeutic use; Budesonide; Budesonide - administration & dosage; Budesonide - therapeutic use; Chronic obstructive pulmonary disease, asthma; Confidence intervals; COPD; Disease Progression; Dose-Response Relationship, Drug; Double-Blind Method; Drug therapy; Ethanolamines - administration & dosage; Ethanolamines - therapeutic use; Exacerbation; Female; Forced Expiratory Volume - drug effects; Formoterol; Formoterol Fumarate; Humans; Male; Medical sciences; Metered Dose Inhalers; Middle Aged; Mortality; Pneumology; Pulmonary Disease, Chronic Obstructive - drug therapy; Pulmonary Disease, Chronic Obstructive - epidemiology; Pulmonary Disease, Chronic Obstructive - physiopathology; Pulmonary/Respiratory; Quality of Life; Randomized; Respiratory Function Tests; Smoking - adverse effects; Smoking - epidemiology; Smoking - physiopathology; Standard deviation; Studies; Treatment; Treatment Outcome; Vital Capacity - drug effects
• ISSN: 0954-6111; 1532-3064
• DOI: 10.1016/j.rmed.2011.07.020

Summary Background Treatment with an inhaled corticosteroid (ICS) and long-acting bronchodilator is recommended for severe/very severe chronic obstructive pulmonary disease (COPD) patients with repeated exacerbations. This randomized, double-blind, double-dummy, parallel-group, 12-month multicenter study evaluated the effect of budesonide/formoterol pressurized metered-dose inhaler (pMDI) on COPD exacerbations. Methods Following a 2-week run-in during which COPD patients aged ≥40 years with an exacerbation history discontinued medications except ICSs, 1219 patients were randomized 1:1:1 to twice-daily budesonide/formoterol pMDI 320/9 μg, budesonide/formoterol pMDI 160/9 μg, or formoterol dry powder inhaler 9 μg. An exacerbation was defined as COPD worsening requiring oral corticosteroids and/or hospitalization. A post hoc analysis, with antibiotic treatment added to the exacerbation definition, was also performed. Results Budesonide/formoterol 320/9 and 160/9 reduced exacerbation rates (number per patient-treatment year) by 34.6% and 25.9%, respectively, versus formoterol ( p  ≤ 0.002). Budesonide/formoterol 320/9 prolonged time to first exacerbation versus formoterol, corresponding to a 21.2% reduction in hazard ratio (0.788 [95% CI: 0.639, 0.972]; p  = 0.026). Exacerbation rates (number per patient-treatment year) including antibiotic treatment (post hoc analysis) were reduced by 25.9% and 18.7% with budesonide/formoterol 320/9 and 160/9, respectively, versus formoterol ( p  ≤ 0.023). Both budesonide/formoterol doses were well tolerated with safety profiles similar to formoterol. Pneumonia adverse events occurred in 6.4%, 4.7%, and 2.7% of patients in the budesonide/formoterol 320/9, 160/9, and formoterol groups. Conclusions Over 12 months, both budesonide/formoterol doses reduced the exacerbation rate (defined with or without antibiotic treatment) versus formoterol. Budesonide/formoterol pMDI is an appropriate treatment for reducing exacerbations in COPD patients with a history of exacerbations. (NCT00419744).