Pneumonia risk with inhaled fluticasone furoate and vilanterol compared with vilanterol alone in patients with COPD.

RATIONALE

Radiographically confirmed pneumonia risk with inhaled corticosteroid use in chronic obstructive pulmonary disease (COPD) has not been assessed to date.

OBJECTIVES

To determine the incidence of pneumonia, risk factors, and clinical attributes with inhaled fluticasone furoate (FF) in patients with COPD with an exacerbation history.

METHODS

Two replicate, 1-year, double-blind clinical trials enrolled subjects with COPD with moderate to very severe airflow limitation and at least one exacerbation within the prior year. Subjects were randomized 1:1:1:1 to receive inhaled once-daily vilanterol (VI) 25 μg or VI 25 μg combined with 50, 100, or 200 μg FF. Subjects were required to have a chest radiograph at screening and within 48 hours of any suspected pneumonia or exacerbation.

MEASUREMENTS AND MAIN RESULTS

Among 3,255 randomized subjects, 205 pneumonia events occurred in 181 subjects. Chest imaging was available for 195 (95%) of these events. Chest radiographs were also obtained for 1,793 (70%) of the 2,545 moderate and severe exacerbations. For VI alone and the combination with 50, 100, or 200 μg FF, reported pneumonia incidence was 3, 6, 6, and 7%, respectively. However, for events with compatible parenchymal infiltrates, the respective incidences were 2, 4, 4, and 5%. Factors associated with at least a twofold increase in the risk of pneumonia with FF/VI treatment were being a current smoker, having prior pneumonia, body mass index <25 kg/m(2), and severe airflow limitation.

CONCLUSIONS

Radiographically confirmed pneumonia risk is increased with inhaled FF/VI, although at less than investigator-defined rates. Modifiable pneumonia risk factors should be considered when attempting to optimize COPD management. Clinical trial registered with www.clinicaltrials.gov (NCT01009463 [HZC102871]; NCT01017952 [HZC102970]).