Efficacy and Tolerability of Budesonide/Formoterol in One Hydrofluoroalkane Pressurized Metered-Dose Inhaler in Patients with Chronic Obstructive Pulmonary Disease Results from a 1-Year Randomized Controlled Clinical Trial

Background: Combination therapy with a long-acting bronchodilator and an inhaled corticosteroid (ICS) is recommended in patients with chronic obstructive pulmonary disease (COPD) who have frequent exacerbations. The efficacy and tolerability of the combination of budesonide/formoterol have been demonstrated in patients with COPD when administered via the dry powder inhaler (DPI) in a 1-year study and when administered via the hydrofluoroalkane (HFA) pressurized metered-dose inhaler (pMDI) in a 6-month study. Objective: This study assessed the long-term efficacy and tolerability of budesonide/formoterol HFA pMDI in patients with moderate to very severe COPD. Methods: This was a 12-month, randomized, double-blind, double-dummy, parallel-group, active- and placebo-controlled, multicentre study (NCT00206167) of 1964 patients aged :40 years with moderate to very severe COPD conducted from 2005 to 2007 at 237 sites in the US, Europe and Mexico. After 2 weeks of treatment based on previous therapy (ICSs, short-acting bronchodilators allowed), patients received one of the following treatments twice daily: budesonide/formoterol pMDI 160/4.5 mu g x two inhalations (320/9 mu g); budesonide/formoterol pMDI 80/4.5 mu g x two inhalations (160/9 mu g); formoterol DPI 4.5 mu g x two inhalations (9 mu g); or placebo. Main outcome measures: The co-primary efficacy variables were pre-dose forced expiratory volume in I second (FEV1) and 1-hour post-dose FEV1. Results: Budesonide/formoterol 320/9 mu g demonstrated greater improvements in pre-dose FEV1 versus formoterol (p = 0.008), and both budesonide/formoterol doses demonstrated greater improvements in 1-hour post-dose FEV1 versus placebo (p < 0.001). The rate of COPD exacerbations was lower in both budesonide/formoterol groups compared with formoterol and placebo (p <= 0.004). Both budesonide/formoterol doses were more effective than placebo (p <= 0.006) for controlling dyspnoea and improving health status (St George's Respiratory Questionnaire). All treatments were generally well tolerated. The incidence of pneumonia was not different for active (3.4-4.0%) and placebo (5.0%) groups. Conclusions: Budesonide/formoterol pMDI (320/9 mu g and 160/9 mu g) improved pulmonary function and reduced symptoms and exacerbations over I year in patients with moderate to very severe COPD. Only budesonide/formoterol pMDI 320/9 mu g demonstrated greater efficacy for both co-primary variables compared with formoterol DPI 9 mu g. Both budesonide/formoterol pMDI dosages were well tolerated relative to formoterol and placebo.