Dupilumab is effective in type 2-high asthma patients receiving high-dose inhaled corticosteroids at baseline

Arnaud Bourdin; Alberto A Papi; Jonathan Corren; J Christian Virchow; Megan S Rice; Yamo Deniz; Michel Djandji; Paul Rowe; Ian D Pavord

doi:10.1111/all.14611

Dupilumab is effective in type 2-high asthma patients receiving high-dose inhaled corticosteroids at baseline

Allergy. 2021 Jan;76(1):269-280. doi: 10.1111/all.14611. Epub 2020 Oct 21.

Authors

Arnaud Bourdin¹, Alberto A Papi², Jonathan Corren³, J Christian Virchow⁴, Megan S Rice⁵, Yamo Deniz⁶, Michel Djandji⁵, Paul Rowe⁷, Ian D Pavord⁸

Affiliations

¹ Department of Respiratory Diseases, INSERM U1046, University of Montpellier, Montpellier, France.
² Università degli Studi di Ferrara, Ferrara, Italy.
³ David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
⁴ Universitätsmedizin Rostock, Rostock, Germany.
⁵ Sanofi, Cambridge, MA, USA.
⁶ Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.
⁷ Sanofi, Bridgewater, NJ, USA.
⁸ University of Oxford, Oxford, UK.

Abstract

Background: Dupilumab blocks the shared receptor component for interleukin (IL)-4/IL-13, key drivers of type 2 inflammation. In phase 2b (NCT01854047) and phase 3 LIBERTY ASTHMA QUEST (NCT02414854), add-on dupilumab 200/300 mg every 2 weeks (q2w) reduced severe exacerbations, improved prebronchodilator (pre-BD) forced expiratory volume in 1 second (FEV₁ ) and quality of life measures, and it was generally well tolerated in patients with uncontrolled, persistent (phase 2b), or moderate-to-severe (phase 3) asthma.

Methods: In patients on high-dose inhaled corticosteroids (ICS) with type 2-high asthma (subgroups including baseline blood eosinophils ≥150/300 cells/µL and/or fractional exhaled nitric oxide [FeNO] ≥25 ppb), annualized severe exacerbation rates over the treatment period, changes from baseline in pre-BD FEV₁ and asthma control (5-item asthma control questionnaire [ACQ-5]) were analyzed.

Results: In high-dose ICS type 2-high subgroups, dupilumab 200/300 mg q2w vs placebo in the phase 2b (24 weeks) and phase 3 (52 weeks) studies significantly reduced severe exacerbations by 55%-69%/57%-60% (all P<.05) and 53%-69%/48%-66% (all P < .001), respectively, except in patients with ≥ 300 eosinophils/µL in phase 2b study (24%/50% (P = .52/0.15). Across subgroups, pre-BD FEV₁ improved by 0.18-0.22 L/0.19-0.24 L (all P < .05) and 0.23-0.36 L/0.15-0.25 L (all P < .01) and ACQ-5 scores were reduced by 0.46-0.55/0.47-0.85 (all P < .05) and 0.38-0.50/0.24-0.30 (all P < .05), respectively, except dupilumab 200 mg q2w in phase 2b in patients with FeNO ≥ 25 ppb (0.41; P = .09). Dupilumab was also effective in patients taking medium-dose ICS.

Conclusion: Dupilumab significantly reduced severe exacerbations and improved lung function and asthma control in patients with type 2-high asthma on high-dose ICS at baseline.

Keywords: asthma control; exacerbations; inhaled corticosteroids; moderate-to-severe asthma; prebronchodilator FEV1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adrenal Cortex Hormones / therapeutic use
Anti-Asthmatic Agents* / therapeutic use
Antibodies, Monoclonal / therapeutic use
Antibodies, Monoclonal, Humanized
Asthma* / diagnosis
Asthma* / drug therapy
Humans
Quality of Life

Substances

Adrenal Cortex Hormones
Anti-Asthmatic Agents
Antibodies, Monoclonal
Antibodies, Monoclonal, Humanized
dupilumab

Associated data

ClinicalTrials.gov/NCT02414854
ClinicalTrials.gov/NCT01854047