PURPOSE:To evaluate the efficacy of budesonide/formoterol administered via one pressurized metered-dose inhaler (pMDI) in chronic obstructive pulmonary disease (COPD).
METHODS:This was a 6-month, randomized, double-blind, multicenter study (NCT00206154) of 1704 patients ≥40 years with moderate to very severe COPD. After 2 weeks of treatment based on previous therapy (inhaled corticosteroids and short-acting bronchodilators allowed), patients received budesonide/formoterol pMDI 160/4.5μg ×2 inhalations (320/9μg), budesonide/formoterol pMDI 80/4.5μg ×2 inhalations (160/9μg), budesonide pMDI 160μg ×2 inhalations (320μg) + formoterol dry powder inhaler (DPI) 4.5μg ×2 inhalations (9μg), budesonide pMDI 160μg ×2 inhalation (320μg), formoterol DPI 4.5μg ×2 inhalations (9μg), or placebo, all twice daily. Assessments included predose and 1-hour postdose forced expiratory volume in 1 second (FEV1, coprimary variables; assessed at randomization and months 1, 2, 4, 6), daily diary variables (morning and evening peak expiratory flow [PEF]; sum of breathlessness, cough, and sputum scores [BCSS, 0=none to 4=severe for each]; awakening-free nights; sleep score [0=none to 4=severe disturbance]; rescue medication), and exacerbation rates.
RESULTS:Both budesonide/formoterol doses demonstrated significantly greater (P≤;.002) improvements from baseline to the average over the treatment period in predose FEV1 and 1-hour postdose FEV1 versus placebo. Predose FEV1 improved significantly from baseline with budesonide/formoterol 320/9μg versus formoterol (P=.026) and with both budesonide/formoterol doses versus budesonide (P≤;.001). Both budesonide/formoterol doses demonstrated significantly (P<.001) greater improvements from baseline in 1-hour postdose FEV1 versus budesonide. Improvements from baseline in morning and evening PEF were significantly (P≤;.016) greater for both budesonide/formoterol doses versus formoterol, budesonide, and placebo. Both budesonide/formoterol doses significantly (P≤;.028) improved BCSS, sleep score, awakening-free nights, and rescue medication use versus placebo. Exacerbation rates were not significantly different but were numerically 20–23% lower for budesonide/formoterol versus placebo.
CONCLUSION:Budesonide/formoterol pMDI 320/9μg twice-daily treatment significantly improved pulmonary function from baseline over 6 months versus its monocomponents and placebo.
CLINICAL IMPLICATIONS:Budesonide/formoterol pMDI 320/9μg twice daily is more effective than budesonide or formoterol for improving pulmonary function in moderate to very severe COPD patients.
DISCLOSURE:Donald Tashkin, University grant monies Dr. Tashkin: AstraZeneca grants to Regents of the University of California: 6-month RCT of Symbicort pMDI in COPD ($7,136) and 1-year RCT of Symbicort pMDI in Hispanic-American patients with asthma ($4,841.27); Shareholder Dr. Goldman and Ms. Martin: AstraZeneca; Employee Drs. Goldman and Silkoff and Ms. Martin: AstraZeneca; Consultant fee, speaker bureau, advisory committee, etc. Dr. Tashkin: AstraZeneca. Dr. Rennard: Abbott, Adams, Almirall, Altana, Anthera, AstraZeneca, GlaxoSmithKline, Johnson & Johnson, Novartis, Pfizer, Roche, Quintiles, TareGen; Product/procedure/technique that is considered research and is NOT yet approved for any purpose. Budesonide/formoterol pMDI is not approved for use in patients with COPD.