PURPOSE:To evaluate the long-term efficacy of budesonide/formoterol pressurized metered-dose inhaler (pMDI) in chronic obstructive pulmonary disease (COPD).
METHODS:This was a 12-month, randomized, double-blind, multicenter study (NCT00206167) of 1964 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), formoterol dry powder inhaler (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 2, 4, 6, 9, 12); 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 symptom]; awakening-free nights; sleep score [0=none to 4=severe disturbance]; rescue medication use), and exacerbation rates.
RESULTS:All active treatments demonstrated significantly greater (P<.001) improvements from baseline to the average over the treatment period in predose and 1-hour postdose FEV1 versus placebo; budesonide/formoterol 320/9μg also demonstrated significantly (P≤;.023) greater improvements versus formoterol, which were not observed with budesonide/formoterol 160/9μg. Improvements from baseline in morning and evening PEF were significantly (P≤;.017) greater for both budesonide/formoterol doses versus formoterol and placebo and significantly (P≤;.012) greater for formoterol versus placebo. Improvements from baseline in BCSS, sleep score, awakening-free nights, and rescue medication use were significantly (P≤;.012) greater for all active treatments versus placebo. Budesonide/formoterol demonstrated significantly (P≤;.038) greater improvements in BCSS (320/9μg only), sleep score, awakening-free nights (160/9μg only), and rescue medication use versus formoterol. Exacerbation rates were significantly (P≤;.004) reduced by ∼25–30% with budesonide/formoterol versus formoterol and ∼40% versus placebo.
CONCLUSION:Budesonide/formoterol pMDI 320/9μg twice daily significantly improved pulmonary function, COPD symptoms, and exacerbations over 12 months versus formoterol and placebo.
CLINICAL IMPLICATIONS:Budesonide/formoterol pMDI 320/9μg twice daily is more effective than formoterol for improving pulmonary function, COPD symptoms, and exacerbations in moderate to very severe COPD patients.
DISCLOSURE:Stephen Rennard, 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); Grant monies (from industry related sources) Dr. Rennard: Almirall, Centocor, GlaxoSmithKline, IFSH, Lorillard, Novartis, Philip Morris, Roche; Shareholder Dr. Goldman: AstraZeneca; Employee Ms. McElhattan and Drs. Goldman and Silkoff: AstraZeneca; Consultant fee, speaker bureau, advisory committee, etc. Dr. Rennard: Adams, Abbott, Almirall, Altana, Anthera, AstraZeneca, GlaxoSmithKline, Johnson & Johnson, Novartis, Pfizer, Roche, Quintiles, TareGen. Dr. Tashkin: AstraZeneca; 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.