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Effect of exacerbation history on clinical response to dupilumab in moderate-severe uncontrolled asthma
PDPI Surakarta, 20 Jul 2021 21:23:05


Background The phase 3 QUEST study (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 12/52, and the 5-item Asthma Control Questionnaire (ACQ-5) score at 24/52 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 fractional exhaled nitric oxide ≥25 ppb and baseline inhaled corticosteroid dose.

Results Across all type 2−high subgroups, dupilumab versus placebo significantly reduced severe exacerbations by 54 to 90%, with greater improvements in patients with more exacerbations prior to study initiation. Similarly, improvements in FEV1 (least squares [LS] difference versus placebo: ≥1 exacerbation, 0.15 to 0.25 L; ≥2 exacerbations, 0.12 to 0.32 L; ≥3 exacerbations, 0.09 to 0.38 L; majority p<0.05) and ACQ-5 score (LS mean difference range: ≥1 exacerbation, −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.

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