Long-term safety and asthma control with budesonide/formoterol versus budesonide pressurized metered-dose inhaler in asthma patients.

Safety concerns have been raised regarding the regular use of long-acting beta(2)-adrenergic agonists (LABAs) alone or with inhaled corticosteroids (ICSs). The purpose of this study was to examine the long-term safety of budesonide/formoterol pressurized metered-dose inhaler (pMDI). This 52-week, double-blind study (SD-039-0728; n=708) included patients >or=12 years of age with moderate to severe persistent asthma previously receiving ICSs. After 2 weeks on budesonide pMDI 320 microg twice daily (b.i.d.), patients were randomized 3:1:1 overall to budesonide/formoterol pMDI 640/18 microg b.i.d., budesonide/formoterol pMDI 320/9 microg b.i.d., or budesonide pMDI 640 microg b.i.d. The incidence of adverse events (AEs) was similar across the groups. Drug-related AEs (>or=2% overall) were oral candidiasis, tremor, and pharyngolaryngeal pain. No clinically meaningful differences in laboratory, electrocardiogram, or Holter monitor variables were observed. The percentage of patients with >or=1 asthma exacerbation was significantly lower (p=0.006) with budesonide/formoterol 640/18 (12.2%) and numerically lower with budesonide/formoterol 320/9 (14.4%) versus budesonide (21.8%). The number of asthma exacerbations per patient-treatment year was lower with budesonide/formoterol 640/18 (0.174; p=0.004) and budesonide/formoterol 320/9 (0.185; p=0.049) versus budesonide (0.315). Improvements in forced expiratory volume in 1 second and diary variables were significantly greater (p<0.001) with both budesonide/formoterol doses versus budesonide. Budesonide/formoterol 640/18 and 320/9 microg b.i.d. showed an acceptable safety profile relative to budesonide, with no significant or unexpected patterns of abnormalities observed by adding a LABA to budesonide for up to 1 year in this patient population. Improvements in asthma control were shown with both doses of budesonide/formoterol versus budesonide.