Effect of budesonide/formoterol pMDI on COPD exacerbations: a double-blind, randomized study.
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).
Section of Pulmonary, Critical Care and Sleep Medicine, Baylor College of Medicine and Michael E. DeBakey VA Medical Center Bldg. 100 (111i), Houston, TX 77030, USA. amirs@bcm.edu
Amir
A
Sharafkhaneh
John G
JG
Southard
Mitchell
M
Goldman
Tom
T
Uryniak
Ubaldo J
UJ
Martin
D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D019819:Budesonide / Q000008:administration & dosage / Q000627:therapeutic use*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004983:Ethanolamines / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D000068759:Formoterol Fumarate; D006801:Humans; D008297:Male; D036501:Metered Dose Inhalers; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology; D011788:Quality of Life; D012129:Respiratory Function Tests; D012907:Smoking / Q000009:adverse effects* / Q000453:epidemiology / Q000503:physiopathology; D016896:Treatment Outcome; D014797:Vital Capacity / Q000187:drug effects
D001993:Bronchodilator Agents; D004983:Ethanolamines; D019819:Budesonide; D000068759:Formoterol Fumarate