Ann Am Thorac Soc. 2020 Oct 27. doi: 10.1513/AnnalsATS.202002-096OC. Online ahead of print.
RATIONALE: In the Informing the Pathway of COPD Treatment (IMPACT) trial, single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) triple therapy reduced exacerbation risk versus FF/VI and UMEC/VI and mortality risk versus UMEC/VI. However, pneumonia incidence was higher in the inhaled corticosteroid (FF)-containing arms raising questions about the relative benefit of exacerbation reduction compared with the increased risk of pneumonia.
OBJECTIVES: Determine benefit-risk of the three treatments by evaluating time-to-first and rates of composite exacerbation or pneumonia outcomes.
METHODS: We evaluated time-to-first (pre-specified) and rates (post hoc) of investigator-reported pneumonia, serious pneumonia leading to hospitalization or death, and the composite endpoints of 1) moderate (required antibiotics/corticosteroids)/severe (hospitalized) exacerbation or pneumonia and 2) severe exacerbation or serious (hospitalized) pneumonia. Analyses were repeated for radiographically confirmed pneumonia (post hoc).
RESULTS: Moderate/severe exacerbations occurred in 47%, 49%, and 50% of patients randomized to FF/UMEC/VI, FF/VI and UMEC/VI, and pneumonias in 8%, 7%, and 5%, respectively. FF/UMEC/VI reduced the risk of combined moderate/severe exacerbation or pneumonia (time-to-first) versus FF/VI (hazard ratio 0.87 [95%CI 0.82-0.92]) and UMEC/VI (0.87 [0.81-0.94]), as well as the risk of combined severe exacerbation or serious pneumonia versus UMEC/VI (0.83 [0.72-0.96]). FF/UMEC/VI reduced the rate of combined moderate/severe exacerbation or pneumonia (rate ratio 0.78 [0.72-0.84]) and combined severe exacerbation or serious pneumonia (rate ratio 0.76 [0.65-0.89]) versus UMEC/VI. Results were similar for radiographically confirmed pneumonia endpoints.
CONCLUSIONS: Despite higher incidence of pneumonia in FF-containing arms, these composite exacerbation/pneumonia outcomes support a favorable benefit-risk profile of FF/UMEC/VI versus FF/VI and UMEC/VI in patients with symptomatic chronic obstructive pulmonary disease and a history of exacerbations.
CLINICAL TRIAL REGISTRATION: CTT116855/NCT02164513.