Monica Kraft1, Guy Brusselle2, J Mark FitzGerald3, Ian D Pavord4, Matthew Keith5, Malin Fagerås6, Esther Garcia Gil7, Ian Hirsch8, Mitchell Goldman5, Gene Colice5. 1. Dept of Medicine, University of Arizona College of Medicine, Tucson, AZ, USA kraftm@email.arizona.edu. 2. Dept of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium. 3. The Centre for Lung Health, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, BC, Canada. 4. Respiratory Medicine Unit and Oxford Respiratory NIHR Biomedical Research Centre, University of Oxford, Oxford, UK. 5. AstraZeneca, Gaithersburg, MD, USA. 6. AstraZeneca, Gothenburg, Sweden. 7. AstraZeneca, Barcelona, Spain. 8. AstraZeneca, Cambridge, UK.
Abstract
BACKGROUND: Greater precision in asthma exacerbation risk prediction may improve outcomes. We sought to identify clinical characteristics and biomarkers associated with elevated exacerbation risk in patients with severe, uncontrolled asthma. METHODS: Data were pooled from seven similarly designed phase II and III randomised controlled clinical trials of biologic therapies for the treatment of severe, uncontrolled asthma that enrolled comparable patient populations. Annualised asthma exacerbation rates (AAERs) for patients randomised to placebo were assessed by baseline clinical characteristics, and by biomarker concentrations at baseline and over the study duration. RESULTS: The AAER for the 2016 patients in the combined placebo group was 0.91 (95% CI 0.84‒0.98). Baseline characteristics associated with greater AAER were frequent or severe exacerbations within the prior 12 months, nasal polyposis, maintenance oral corticosteroid use, Asian race and Asian or Western European region. AAER increased with baseline blood eosinophil counts and exhaled nitric oxide fraction (F ENO) concentration, with the greatest AAER occurring for patients with eosinophils ≥300 cells·μL-1 and F ENO ≥50 ppb. No relationship was observed between baseline serum IgE concentration and AAER. Combining type 2 inflammation criteria for eosinophils and F ENO had greater prognostic value than either biomarker alone. Persistent eosinophil and F ENO elevations throughout the study period were associated with greater AAER. CONCLUSIONS: Exacerbation history, maintenance corticosteroid use, nasal polyposis, Asian race, geographic region, and elevations in blood eosinophil counts and F ENO concentrations (particularly when combined and/or persistently achieving type 2 inflammation criteria) were associated with increased exacerbation risk in patients with severe, uncontrolled asthma.
BACKGROUND: Greater precision in asthma exacerbation risk prediction may improve outcomes. We sought to identify clinical characteristics and biomarkers associated with elevated exacerbation risk in patients with severe, uncontrolled asthma. METHODS: Data were pooled from seven similarly designed phase II and III randomised controlled clinical trials of biologic therapies for the treatment of severe, uncontrolled asthma that enrolled comparable patient populations. Annualised asthma exacerbation rates (AAERs) for patients randomised to placebo were assessed by baseline clinical characteristics, and by biomarker concentrations at baseline and over the study duration. RESULTS: The AAER for the 2016 patients in the combined placebo group was 0.91 (95% CI 0.84‒0.98). Baseline characteristics associated with greater AAER were frequent or severe exacerbations within the prior 12 months, nasal polyposis, maintenance oral corticosteroid use, Asian race and Asian or Western European region. AAER increased with baseline blood eosinophil counts and exhaled nitric oxide fraction (F ENO) concentration, with the greatest AAER occurring for patients with eosinophils ≥300 cells·μL-1 and F ENO ≥50 ppb. No relationship was observed between baseline serum IgE concentration and AAER. Combining type 2 inflammation criteria for eosinophils and F ENO had greater prognostic value than either biomarker alone. Persistent eosinophil and F ENO elevations throughout the study period were associated with greater AAER. CONCLUSIONS: Exacerbation history, maintenance corticosteroid use, nasal polyposis, Asian race, geographic region, and elevations in blood eosinophil counts and F ENO concentrations (particularly when combined and/or persistently achieving type 2 inflammation criteria) were associated with increased exacerbation risk in patients with severe, uncontrolled asthma.