Dupilumab improves lung function in patients with uncontrolled, moderate-to-severe asthma

Mario Castro; Klaus F. Rabe; Jonathan Corren; Ian D. Pavord; Constance H. Katelaris; Yuji Tohda; Bingzhi Zhang; Megan S. Rice; Jaman Maroni; Paul Rowe; Gianluca Pirozzi; Nikhil Amin; Marcella Ruddy; Bolanle Akinlade; Neil M. H. Graham; Ariel Teper

doi:10.1183/23120541.00204-2019

Dupilumab improves lung function in patients with uncontrolled, moderate-to-severe asthma

Mario Castro
, Klaus F. Rabe
, Jonathan Corren
, Ian D. Pavord
, Constance H. Katelaris
, Yuji Tohda
, Bingzhi Zhang
, Megan S. Rice
, Jaman Maroni
, Paul Rowe
, Gianluca Pirozzi
, Nikhil Amin
, Marcella Ruddy
, Bolanle Akinlade
, Neil M. H. Graham
, Ariel Teper

Research output: Contribution to journal › Article › peer-review

53 Citations (Scopus)

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Abstract

Background: Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4 and interleukin-13, key drivers of type 2 inflammation. In the phase 3 LIBERTY ASTHMA QUEST trial (NCT02414854) in patients with uncontrolled, moderate-to-severe asthma, add-on dupilumab 200 mg or 300 mg every 2 weeks reduced exacerbations and improved forced expiratory volume in 1 s (FEV₁) and quality of life over 52 weeks. This analysis evaluates dupilimab’s effect on lung function in the overall population, and subgroups with baseline elevated type 2 inflammatory biomarkers. Methods: Patients were randomised to 52 weeks of subcutaneous dupilumab 200 mg every 2 weeks, 300 mg every 2 weeks, or matched-volume placebos. Lung function outcomes were analysed in the overall population, in patients with ≥150 eosinophils·µL⁻¹, ≥300 eosinophils·µL⁻¹, ≥25 ppb fractional exhaled nitric oxide (F_eNO), and both ≥150 eosinophils·µL⁻¹ and ≥25 ppb F_eNO, at baseline. Results: Dupilumab treatment (200 mg and 300 mg every 2 weeks) resulted in significant improvements versus placebo after 52 weeks in pre-bronchodilator FEV₁ (0.20 and 0.13 L, respectively, versus placebo) and post-bronchodilator FEV₁ (0.19 and 0.13 L, respectively), forced vital capacity (FVC) (0.20 and 0.14 L, respectively), forced expiratory flow (0.19 and 0.13 L·s⁻¹, respectively) and pre-bronchodilator FEV₁/FVC ratio (1.75% and 1.61%, respectively) in the overall population (p<0.001). Difference versus placebo in post-bronchodilator FEV₁ slope ofchange(weeks4–52) was significant (0.04 L·year⁻¹; p<0.05). Greater improvements were achieved in patients with elevated baseline blood eosinophil and/or F_eNO levels for most outcomes. Conclusions: Dupilumab improves lung function outcomes, including large and small airway measurements and fixed airway obstruction, in patients with uncontrolled, moderate-to-severe asthma; particularly in patients with elevated biomarkers of type 2 inflammation.

Original language	English
Article number	00204-2019
Number of pages	11
Journal	ERJ Open Research
Volume	6
Issue number	1
DOIs	https://doi.org/10.1183/23120541.00204-2019
Publication status	Published - 1 Jan 2020

Bibliographical note

Publisher Copyright:
© ERS 2020.

Open Access - Access Right Statement

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

anti, inflammatory agents
asthma
inflammation
interleukins
lungs

Access to Document

10.1183/23120541.00204-2019

dupilumab_open access

Cite this

Castro, M., Rabe, K. F., Corren, J., Pavord, I. D., Katelaris, C. H., Tohda, Y., Zhang, B., Rice, M. S., Maroni, J., Rowe, P., Pirozzi, G., Amin, N., Ruddy, M., Akinlade, B., Graham, N. M. H., & Teper, A. (2020). Dupilumab improves lung function in patients with uncontrolled, moderate-to-severe asthma. ERJ Open Research, 6(1), Article 00204-2019. https://doi.org/10.1183/23120541.00204-2019

@article{872ebb5d3d4544c19b6f96f27c3c81db,

title = "Dupilumab improves lung function in patients with uncontrolled, moderate-to-severe asthma",

abstract = "Background: Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4 and interleukin-13, key drivers of type 2 inflammation. In the phase 3 LIBERTY ASTHMA QUEST trial (NCT02414854) in patients with uncontrolled, moderate-to-severe asthma, add-on dupilumab 200 mg or 300 mg every 2 weeks reduced exacerbations and improved forced expiratory volume in 1 s (FEV1) and quality of life over 52 weeks. This analysis evaluates dupilimab{\textquoteright}s effect on lung function in the overall population, and subgroups with baseline elevated type 2 inflammatory biomarkers. Methods: Patients were randomised to 52 weeks of subcutaneous dupilumab 200 mg every 2 weeks, 300 mg every 2 weeks, or matched-volume placebos. Lung function outcomes were analysed in the overall population, in patients with ≥150 eosinophils·µL−1, ≥300 eosinophils·µL−1, ≥25 ppb fractional exhaled nitric oxide (FeNO), and both ≥150 eosinophils·µL−1 and ≥25 ppb FeNO, at baseline. Results: Dupilumab treatment (200 mg and 300 mg every 2 weeks) resulted in significant improvements versus placebo after 52 weeks in pre-bronchodilator FEV1 (0.20 and 0.13 L, respectively, versus placebo) and post-bronchodilator FEV1 (0.19 and 0.13 L, respectively), forced vital capacity (FVC) (0.20 and 0.14 L, respectively), forced expiratory flow (0.19 and 0.13 L·s−1, respectively) and pre-bronchodilator FEV1/FVC ratio (1.75\% and 1.61\%, respectively) in the overall population (p<0.001). Difference versus placebo in post-bronchodilator FEV1 slope ofchange(weeks4{\textendash}52) was significant (0.04 L·year−1; p<0.05). Greater improvements were achieved in patients with elevated baseline blood eosinophil and/or FeNO levels for most outcomes. Conclusions: Dupilumab improves lung function outcomes, including large and small airway measurements and fixed airway obstruction, in patients with uncontrolled, moderate-to-severe asthma; particularly in patients with elevated biomarkers of type 2 inflammation.",

keywords = "anti, inflammatory agents, asthma, inflammation, interleukins, lungs",

author = "Mario Castro and Rabe, \{Klaus F.\} and Jonathan Corren and Pavord, \{Ian D.\} and Katelaris, \{Constance H.\} and Yuji Tohda and Bingzhi Zhang and Rice, \{Megan S.\} and Jaman Maroni and Paul Rowe and Gianluca Pirozzi and Nikhil Amin and Marcella Ruddy and Bolanle Akinlade and Graham, \{Neil M. H.\} and Ariel Teper",

note = "Publisher Copyright: {\textcopyright} ERS 2020.",

year = "2020",

month = jan,

day = "1",

doi = "10.1183/23120541.00204-2019",

language = "English",

volume = "6",

journal = "ERJ Open Research",

issn = "2312-0541",

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TY - JOUR

T1 - Dupilumab improves lung function in patients with uncontrolled, moderate-to-severe asthma

AU - Castro, Mario

AU - Rabe, Klaus F.

AU - Corren, Jonathan

AU - Pavord, Ian D.

AU - Katelaris, Constance H.

AU - Tohda, Yuji

AU - Zhang, Bingzhi

AU - Rice, Megan S.

AU - Maroni, Jaman

AU - Rowe, Paul

AU - Pirozzi, Gianluca

AU - Amin, Nikhil

AU - Ruddy, Marcella

AU - Akinlade, Bolanle

AU - Graham, Neil M. H.

AU - Teper, Ariel

PY - 2020/1/1

Y1 - 2020/1/1

N2 - Background: Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4 and interleukin-13, key drivers of type 2 inflammation. In the phase 3 LIBERTY ASTHMA QUEST trial (NCT02414854) in patients with uncontrolled, moderate-to-severe asthma, add-on dupilumab 200 mg or 300 mg every 2 weeks reduced exacerbations and improved forced expiratory volume in 1 s (FEV1) and quality of life over 52 weeks. This analysis evaluates dupilimab’s effect on lung function in the overall population, and subgroups with baseline elevated type 2 inflammatory biomarkers. Methods: Patients were randomised to 52 weeks of subcutaneous dupilumab 200 mg every 2 weeks, 300 mg every 2 weeks, or matched-volume placebos. Lung function outcomes were analysed in the overall population, in patients with ≥150 eosinophils·µL−1, ≥300 eosinophils·µL−1, ≥25 ppb fractional exhaled nitric oxide (FeNO), and both ≥150 eosinophils·µL−1 and ≥25 ppb FeNO, at baseline. Results: Dupilumab treatment (200 mg and 300 mg every 2 weeks) resulted in significant improvements versus placebo after 52 weeks in pre-bronchodilator FEV1 (0.20 and 0.13 L, respectively, versus placebo) and post-bronchodilator FEV1 (0.19 and 0.13 L, respectively), forced vital capacity (FVC) (0.20 and 0.14 L, respectively), forced expiratory flow (0.19 and 0.13 L·s−1, respectively) and pre-bronchodilator FEV1/FVC ratio (1.75% and 1.61%, respectively) in the overall population (p<0.001). Difference versus placebo in post-bronchodilator FEV1 slope ofchange(weeks4–52) was significant (0.04 L·year−1; p<0.05). Greater improvements were achieved in patients with elevated baseline blood eosinophil and/or FeNO levels for most outcomes. Conclusions: Dupilumab improves lung function outcomes, including large and small airway measurements and fixed airway obstruction, in patients with uncontrolled, moderate-to-severe asthma; particularly in patients with elevated biomarkers of type 2 inflammation.

AB - Background: Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4 and interleukin-13, key drivers of type 2 inflammation. In the phase 3 LIBERTY ASTHMA QUEST trial (NCT02414854) in patients with uncontrolled, moderate-to-severe asthma, add-on dupilumab 200 mg or 300 mg every 2 weeks reduced exacerbations and improved forced expiratory volume in 1 s (FEV1) and quality of life over 52 weeks. This analysis evaluates dupilimab’s effect on lung function in the overall population, and subgroups with baseline elevated type 2 inflammatory biomarkers. Methods: Patients were randomised to 52 weeks of subcutaneous dupilumab 200 mg every 2 weeks, 300 mg every 2 weeks, or matched-volume placebos. Lung function outcomes were analysed in the overall population, in patients with ≥150 eosinophils·µL−1, ≥300 eosinophils·µL−1, ≥25 ppb fractional exhaled nitric oxide (FeNO), and both ≥150 eosinophils·µL−1 and ≥25 ppb FeNO, at baseline. Results: Dupilumab treatment (200 mg and 300 mg every 2 weeks) resulted in significant improvements versus placebo after 52 weeks in pre-bronchodilator FEV1 (0.20 and 0.13 L, respectively, versus placebo) and post-bronchodilator FEV1 (0.19 and 0.13 L, respectively), forced vital capacity (FVC) (0.20 and 0.14 L, respectively), forced expiratory flow (0.19 and 0.13 L·s−1, respectively) and pre-bronchodilator FEV1/FVC ratio (1.75% and 1.61%, respectively) in the overall population (p<0.001). Difference versus placebo in post-bronchodilator FEV1 slope ofchange(weeks4–52) was significant (0.04 L·year−1; p<0.05). Greater improvements were achieved in patients with elevated baseline blood eosinophil and/or FeNO levels for most outcomes. Conclusions: Dupilumab improves lung function outcomes, including large and small airway measurements and fixed airway obstruction, in patients with uncontrolled, moderate-to-severe asthma; particularly in patients with elevated biomarkers of type 2 inflammation.

KW - anti, inflammatory agents

KW - asthma

KW - inflammation

KW - interleukins

KW - lungs

UR - http://hdl.handle.net/1959.7/uws:56621

UR - https://www.scopus.com/pages/publications/85089252503

U2 - 10.1183/23120541.00204-2019

DO - 10.1183/23120541.00204-2019

M3 - Article

SN - 2312-0541

VL - 6

JO - ERJ Open Research

JF - ERJ Open Research

IS - 1

M1 - 00204-2019

ER -

Dupilumab improves lung function in patients with uncontrolled, moderate-to-severe asthma

Abstract

Bibliographical note

Open Access - Access Right Statement

UN SDGs

Keywords

Access to Document

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