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  • S49 Dupilumab improves lung function across baseline disease characteristics in patients with evidence of type 2 inflammation at baseline: the LIBERTY ASTHMA QUEST study

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Increasing experience of biologics and asthma
S49 Dupilumab improves lung function across baseline disease characteristics in patients with evidence of type 2 inflammation at baseline: the LIBERTY ASTHMA QUEST study
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  1. P Paggiaro1,
  2. M Castro2,
  3. WG Canonica3,
  4. JA Douglass4,5,
  5. Y Tohda6,
  6. MS Rice7,
  7. Y Deniz8,
  8. P Rowe9,
  9. N Amin8,
  10. A Teper9
  1. 1University of Pisa, Pisa, Italy
  2. 2Washington University School of Medicine, St. Louis, USA
  3. 3Humanitas University and Research Hospital, Milan, Italy
  4. 4Royal Melbourne Hospital, Melbourne, Australia
  5. 5The University of Melbourne, Melbourne, Australia
  6. 6Kindai University, Osakasayama, Japan
  7. 7Sanofi, Cambridge, USA
  8. 8Regeneron Pharmaceuticals, Inc., Tarrytown, USA
  9. 9Sanofi, Bridgewater, USA

Abstract

Introduction Dupilumab, a fully human VelocImmune®-derived monoclonal antibody, blocks the shared receptor component for interleukin (IL)-4/IL-13, key drivers of type 2 inflammation in multiple diseases. In the phase 3 LIBERTY ASTHMA QUEST study (NCT02414854), add-on dupilumab 200 mg/300 mg every 2 weeks (q2w) vs placebo reduced severe exacerbations and improved pre-bronchodilator forced expiratory volume in 1 second (FEV1) in patients with uncontrolled, moderate-to-severe asthma. Treatment effects were greater in patients with elevated type 2 biomarkers at baseline. This post hoc analysis assessed the effects of dupilumab on pre-bronchodilator FEV1 by baseline disease characteristics in patients with baseline levels of blood eosinophils ≥150 cells/µL or fractional exhaled nitric oxide (FeNO) ≥20 ppb, biomarkers of type 2 inflammation. 

Methods Least squares (LS) mean changes from baseline to Week 12 in pre-bronchodilator FEV1 were assessed using mixed-effect models with repeated measures.

Results Dupilumab 200 mg/300 mg q2w vs placebo improved pre-bronchodilator FEV1 in patients with elevated type 2 biomarkers in subgroups defined by controller medications at randomization, baseline pre-bronchodilator FEV1 (≤1.75 L/>1.75 L), number of severe asthma exacerbations (≥1, ≥2, ≥3) in the previous year, smoking history (never smoked/former smoker with a smoking history ≤10 pack-years), and age at asthma onset (≤40 years/>40 years) (figure). The effect of dupilumab was significant in all subgroups except for a couple of subgroups of patients with type 2 inflammation on triple asthma controllers and those who were former smokers. Overall, the most frequent dupilumab 200 mg/300 mg vs matched placebo adverse event was injection-site reaction (15%/18% vs 5%/10%).

Conclusions Dupilumab significantly improved pre-bronchodilator FEV1 across most baseline disease characteristics in patients with uncontrolled, moderate-to-severe asthma with evidence of type 2 inflammation at baseline. Dupilumab was generally well tolerated.

Abstract S49 Figure 1
Abstract S49 Figure 1

Change in pre-bronchodilator FEV1 from baseline to Week 12 by baseline disease characteristics in patients with uncontrolled, moderate-to-severe asthma and elevated type 2 biomarkers at baseline (blood eosinophils ≥150 cells/µL or FeNO ≥ 20ppb

https://doi.org/10.1136/thorax-2019-BTSabstracts2019.55

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