| Summary: | Ian D Pavord,1 Salman Siddiqui,2 Alberto Papi,3 Jonathan Corren,4 Lawrence D Sher,5 Philip Bardin,6 David Langton,7 Hae-Sim Park,8 Megan S Rice,9 Yamo Deniz,10 Paul Rowe,11 Heribert W Staudinger,11 Naimish Patel,11 Marcella Ruddy,10 Neil MH Graham,10 Ariel Teper11 1Respiratory Medicine Unit and Oxford Respiratory National Institute for Health Research Biomedical Research Centre, University of Oxford, Oxford, UK; 2University of Leicester and Leicester National Institute for Health Research Biomedical Research Centre (Respiratory Theme), Leicester, UK; 3Department of Respiratory Medicine, University of Ferrara, Ferrara, Italy; 4David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; 5Peninsula Research Associates, Rolling Hills Estate, CA, USA; 6Department of Lung and Sleep Medicine, Monash University and Medical Centre, Clayton, Melbourne, VIC, Australia; 7Department of Thoracic Medicine, Frankston Hospital, Frankston, Melbourne, VIC, Australia; 8Ajou University Hospital, Suwon, South Korea; 9Sanofi, Cambridge, MA, USA; 10Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA; 11Sanofi, Bridgewater, NJ, USACorrespondence: Ian D PavordNDM Research Building, Nuffield Department of Medicine, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7FZ, UKTel +44 (0)1865 612897Email ian.pavord@ndm.ox.ac.ukPurpose: The Phase 3 LIBERTY ASTHMA QUEST study in patients aged ≥ 12 years with uncontrolled, moderate-to-severe asthma demonstrated the efficacy and safety of dupilumab 200 mg and 300 mg every 2 weeks (q2w) vs matched placebo in the overall population. This post hoc analysis assessed dupilumab efficacy by disease severity as evidenced by baseline % predicted forced expiratory volume in 1 second (FEV1) and dose of inhaled corticosteroids (ICS).Patients and Methods: Severe asthma exacerbation rates, change from baseline in FEV1, asthma control, quality of life, and fractional exhaled nitric oxide (FeNO) levels over the 52-week treatment period were assessed in patients with elevated type 2 inflammation biomarkers stratified by ICS dose and FEV1% predicted at baseline.Results: In patients with elevated baseline eosinophils, dupilumab 200 mg and 300 mg q2w vs placebo reduced severe exacerbation rates by 50% (P=0.06) and 67% (P=0.001), respectively, in those with medium-dose ICS/FEV1% predicted 60– 90%, and by 59% (P< 0.001) and 47% (P=0.006) in those with high-dose ICS/FEV1% predicted < 60%, improved pre-bronchodilator FEV1 at Week 12 by 0.16L (P=0.005) and 0.08L (P=0.13), and by 0.20L (P=0.003) and 0.21L (P< 0.001), respectively, in the same subgroups. Dupilumab vs placebo also improved asthma control and quality of life and suppressed FeNO levels in all patient subgroups with similar results observed irrespective of baseline biomarker status or disease severity.Conclusion: Dupilumab reduced severe exacerbations and improved lung function, asthma control and quality of life in patients with elevated baseline eosinophils irrespective of baseline ICS dose or FEV1% predicted.Keywords: asthma, biomarkers, dupilumab, exacerbation, FEV1
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