Effect of exacerbation history on clinical response to dupilumab in moderate-to-severe uncontrolled asthma

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 center dot mu L-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.