TY - JOUR T1 - Effect of exacerbation history on clinical response to dupilumab in moderate-to-severe uncontrolled asthma JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.04498-2020 VL - 58 IS - 4 SP - 2004498 AU - Jonathan Corren AU - Constance H. Katelaris AU - Mario Castro AU - Jorge F. Maspero AU - Linda B. Ford AU - David M.G. Halpin AU - Megan S. Rice AU - Amr Radwan AU - Yamo Deniz AU - Paul J. Rowe AU - Ariel Teper AU - Michel Djandji Y1 - 2021/10/01 UR - http://erj.ersjournals.com/content/58/4/2004498.abstract N2 - Background The phase 3 LIBERTY ASTHMA QUEST study (ClinicalTrials.gov: NCT02414854) in patients with uncontrolled, moderate-to-severe asthma has demonstrated the efficacy and safety of dupilumab 200 and 300 mg every 2 weeks versus placebo. This post hoc analysis assessed the effect of dupilumab on efficacy outcomes and asthma control across a range of historical exacerbation rates in patients with type 2-high asthma.Methods Annualised severe exacerbation rates over the 52-week treatment period, pre-bronchodilator forced expiratory volume in 1 s (FEV1) at weeks 12 and 52, and the five-item Asthma Control Questionnaire (ACQ-5) score at weeks 24 and 52 were assessed in patients with ≥1, ≥2 or ≥3 exacerbations in the previous year. Subgroups were stratified by baseline blood eosinophils ≥150 or ≥300 cells·μL−1 or baseline exhaled nitric oxide fraction ≥25 ppb and baseline inhaled corticosteroid (ICS) dose.Results Across all type 2-high subgroups, dupilumab versus placebo significantly reduced severe exacerbations by 54–90%, with greater improvements in patients with more exacerbations prior to study initiation. Similarly, improvements in FEV1 (least squares (LS) mean difference versus placebo: ≥1 exacerbations, 0.15–0.25 L; ≥2 exacerbations, 0.12–0.32 L; ≥3 exacerbations, 0.09–0.38 L; majority p<0.05) and ACQ-5 score (LS mean difference range: ≥1 exacerbations, −0.30 to −0.57; ≥2 exacerbations, −0.29 to −0.56; ≥3 exacerbations, −0.43 to −0.61; all p<0.05) were observed, irrespective of prior exacerbation history, across all subgroups.Conclusions Dupilumab significantly reduced severe exacerbations and improved FEV1 and asthma control in patients with elevated type 2 biomarkers irrespective of exacerbation history and baseline ICS dose.Dupilumab reduced severe exacerbations and improved lung function and asthma control in patients with type 2-high asthma, irrespective of exacerbation history and baseline ICS dose. These data will aid clinicians managing patients with severe disease. https://bit.ly/2PjnSm6 ER -