Courtney Crim1, Peter M A Calverley2, Julie A Anderson3, Andrew P Holmes4, Sally Kilbride3, Fernando J Martinez5, Robert D Brook6, David E Newby7, Julie C Yates8, Bartolomé R Celli9, Jørgen Vestbo10. 1. GlaxoSmithKline, Research Triangle Park, USA. Electronic address: Courtney.c.crim@gsk.com. 2. University Hospital Aintree, Liverpool, UK. 3. GSK R&D, Stockley Park, UK. 4. Veramed Limited, Twickenham, UK. 5. NewYork-Presbyterian Hospital/Weill Cornell Medical Center, New York, USA. 6. University of Michigan Health System, Ann Arbor, USA. 7. University of Edinburgh, Edinburgh, UK. 8. GlaxoSmithKline, Research Triangle Park, USA. 9. Brigham and Women's Hospital, Harvard Medical School, Boston, USA. 10. University of Manchester and University Hospital South Manchester NHS Foundation Trust, Manchester, UK.
Abstract
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.
RCT Entities:
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 COPDpatients 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.
Authors: Emily P Brigham; Julie A Anderson; Robert D Brook; Peter M A Calverley; Bartolome R Celli; Nicholas J Cowans; Courtney Crim; James E Diserens; Fernando J Martinez; Meredith C McCormack; David E Newby; Julie Yates; Jorgen Vestbo; Tianshi David Wu; Robert A Wise Journal: ERJ Open Res Date: 2021-07-26