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<h4>Background</h4>Dupilumab blocks the shared receptor component for IL-4 and IL-13, key drivers of type 2 inflammation, including IgE-mediated allergic inflammation in asthma. In the LIBERTY ASTHMA QUEST (NCT02414854) study, dupilumab reduced severe asthma exacerbations and improved forced expiratory volume in 1 second (FEV<sub>1</sub>) in patients with uncontrolled, moderate-to-severe asthma with greater efficacy observed in patients with elevated type 2 inflammatory biomarkers (blood eosinophils and fractional exhaled nitric oxide) at baseline.<h4>Objective</h4>We assessed dupilumab's effect on key asthma outcomes in QUEST patients with/without evidence of allergic asthma (total serum IgE ≥30 IU/mL and ≥1 perennial aeroallergen-specific IgE ≥0.35 kU/L at baseline).<h4>Methods</h4>Severe exacerbation rates and change from baseline in FEV<sub>1</sub>, asthma control, and markers of type 2 inflammation during the 52-week treatment period were assessed.<h4>Results</h4>In the allergic asthma subgroup (n = 1083), dupilumab 200/300 mg every 2 weeks versus placebo reduced severe asthma exacerbation rates (-36.9%/-45.5%; both P < .01), improved FEV<sub>1</sub> at week 12 (0.13 L/0.16 L; both P < .001; improvements were evident by the first evaluation at week 2) with greater efficacy observed in patients with elevated type 2 inflammatory biomarkers at baseline, and improved asthma control. Dupilumab treatment also resulted in rapid and sustained reductions in type 2 inflammatory biomarkers. Comparable results were observed in patients without evidence of allergic asthma (n = 819).<h4>Conclusion</h4>Dupilumab reduced severe exacerbation rates, improved FEV<sub>1</sub> and asthma control, and suppressed type 2 inflammatory biomarkers in patients with uncontrolled, moderate-to-severe asthma with or without evidence of allergic asthma, highlighting the key role of IL-4 and IL-13 in airway inflammation.

Original publication

DOI

10.1016/j.jaip.2019.08.050

Type

Journal article

Journal

The journal of allergy and clinical immunology. In practice

Publication Date

02/2020

Volume

8

Pages

516 - 526

Addresses

David Geffen School of Medicine at UCLA, Los Angeles, Calif. Electronic address: jcorren@ucla.edu.