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A randomised, placebo-controlled trial evaluating effects of lebrikizumab on airway eosinophilic inflammation and remodelling in uncontrolled asthma (CLAVIER).

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posted on 29.09.2020, 09:04 by Cary D Austin, Melissa Gonzalez Edick, Ronald E Ferrando, Margaret Solon, Miriam Baca, Kathryn Mesh, Peter Bradding, Gail M Gauvreau, Kaharu Sumino, J Mark FitzGerald, Elliot Israel, Lief Bjermer, Arnaud Bourdin, Joseph R Arron, David F Choy, Julie K Olsson, Francis Abreu, Monet Howard, Kit Wong, Fang Cai, Kun Peng, Wendy S Putnam, Cécile TJ Holweg, John G Matthews, Monica Kraft, Prescott G Woodruff, CLAVIER Investigators
BACKGROUND:The anti-interleukin 13 (IL-13) monoclonal antibody lebrikizumab improves lung function in patients with moderate to severe uncontrolled asthma, but its effects on airway inflammation and remodelling are unknown. CLAVIER was designed to assess lebrikizumab's effect on eosinophilic inflammation and remodelling.
OBJECTIVE:To report safety and efficacy results from enrolled participants with available data from CLAVIER.
METHODS:We performed bronchoscopy on patients with uncontrolled asthma before and after 12 weeks of randomised double-blinded treatment with lebrikizumab (n=31) or placebo (n=33). The pre-specified primary endpoint was relative change in airway subepithelial eosinophils per mm2 of basement membrane (cells/mm2 ). Pre-specified secondary and exploratory outcomes included change in IL-13-associated biomarkers and measures of airway remodelling.
RESULTS:There was a baseline imbalance in tissue eosinophils and high variability between treatment groups. There was no discernible change in adjusted mean subepithelial eosinophils/mm2 in response to lebrikizumab (95% CI, -82.5%, 97.5%). As previously observed, FEV1 increased after lebrikizumab treatment. Moreover, subepithelial collagen thickness decreased 21.5% after lebrikizumab treatment (95% CI, -32.9%, -10.2%), and fractional exhaled nitric oxide, CCL26, and SERPINB2 mRNA expression in bronchial tissues also reduced. Lebrikizumab was well tolerated, with a safety profile consistent with other lebrikizumab asthma studies.
CONCLUSIONS & CLINICAL RELEVANCE:We did not observe reduced tissue eosinophil numbers in association with lebrikizumab treatment. However, in pre-specified exploratory analyses, lebrikizumab treatment was associated with reduced degree of subepithelial fibrosis, a feature of airway remodelling, as well as improved lung function and reduced key pharmacodynamic biomarkers in bronchial tissues. These results reinforce the importance of IL-13 in airway pathobiology and suggest that neutralisation of IL-13 may reduce asthmatic airway remodelling.

History

Citation

Clinical and experimental allergy, 2020, https://doi.org/10.1111/cea.13731

Author affiliation

Department of Respiratory Sciences, University of Leicester

Version

AM (Accepted Manuscript)

Published in

Clinical and experimental allergy

Publisher

Wiley

issn

0954-7894

eissn

1365-2222

Copyright date

2020

Available date

10/09/2021

Spatial coverage

England

Language

eng

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