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Patient characteristics, biomarkers, and exacerbation risk in 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 randomized controlled clinical trials of biologic therapies for the treatment of severe, uncontrolled asthma that enrolled comparable patient populations. Annualized asthma exacerbation rates (AAERs) for patients randomized 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 fractional exhaled nitric oxide (FeNO) concentration, with the greatest AAER occurring for patients with eosinophils ≥300 cells·μL-1 and FeNO ≥50 ppb. No relationship was observed between baseline serum immunoglobulin E concentration and AAER. Combining type 2 inflammation criteria for eosinophils and FeNO had greater prognostic value than either biomarker alone. Persistent eosinophil and FeNO 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 FeNO concentrations (particularly when combined and/or persistently achieving type 2 inflammation criteria) were associated with increased exacerbation risk in patients with severe, uncontrolled asthma.