Pneumonia risk with inhaled fluticasone furoate and vilanterol in COPD patients with moderate airflow limitation: The SUMMIT trial.

RATIONALE: Pneumonia risk with inhaled corticosteroid use in chronic obstructive pulmonary disease (COPD) has not been thoroughly assessed in patients with moderate airflow limitation. OBJECTIVES: To determine the incidence of pneumonia and risk factors in COPD patients with moderate airflow limitation who had, or were at high risk for cardiovascular disease. METHODS: In the Study to Understand Mortality and MorbidITy in COPD (SUMMIT), 16,590 subjects with moderate airflow limitation (50% ≤ FEV1 ≤ 70% predicted) and heightened cardiovascular risk were randomized double-blind 1:1:1:1 to inhaled once-daily vilanterol 25 μg (VI), fluticasone furoate 100 μg (FF), vilanterol 25 μg combined with 100 μg fluticasone furoate (FF/VI), or matched placebo. In a pre-specified analysis, we assessed investigator-reported adverse pneumonia events, and independently-adjudicated fatal events. MEASUREMENTS AND MAIN RESULTS: The safety population comprised 16,568 subjects who actually received study medication. There were 1017 pneumonia events reported from 842 subjects. For placebo, FF, VI and FF/VI, reported pneumonia incidence was 5%, 5%, 4% and 6%, respectively. When adjusted for time on treatment, event rates were similar in the placebo, FF and FF/VI containing arms (3.84, 4.24 and 3.95/100 treatment years, respectively) but lower in the VI group (2.77/100 treatment years). Risk factors for pneumonia risk included: greater degree of airflow limitation (i.e. FEV1 <60% predicted), prior exacerbation history, and BMI <25 kg/m2. CONCLUSIONS: In contrast to previous studies in patients with severe disease, increased pneumonia risk with inhaled corticosteroid use was not evident in COPD subjects with moderate airflow limitation and heightened cardiovascular risk.