A randomized, placebo-controlled trial evaluating effects of lebrikizumab on airway eosinophilic inflammation and remodelling in uncontrolled asthma (CLAVIER).
Adolescent
Adult
Aged
Airway Remodeling
/ drug effects
Anti-Asthmatic Agents
/ adverse effects
Antibodies, Monoclonal
/ adverse effects
Asthma
/ drug therapy
Double-Blind Method
Eosinophils
/ drug effects
Female
Humans
Interleukin-13
/ antagonists & inhibitors
Lung
/ drug effects
Male
Middle Aged
Signal Transduction
Time Factors
Treatment Outcome
Young Adult
Journal
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
ISSN: 1365-2222
Titre abrégé: Clin Exp Allergy
Pays: England
ID NLM: 8906443
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
30
03
2020
revised:
16
07
2020
accepted:
31
08
2020
pubmed:
11
9
2020
medline:
3
11
2021
entrez:
10
9
2020
Statut:
ppublish
Résumé
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. To report safety and efficacy results from enrolled participants with available data from CLAVIER. We performed bronchoscopy on patients with uncontrolled asthma before and after 12 weeks of randomized double-blinded treatment with lebrikizumab (n = 31) or placebo (n = 33). The pre-specified primary end-point was relative change in airway subepithelial eosinophils per mm There was a baseline imbalance in tissue eosinophils and high variability between treatment groups. There was no discernible change in adjusted mean subepithelial eosinophils/mm 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 neutralization of IL-13 may reduce asthmatic airway remodelling. NCT02099656.
Sections du résumé
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 randomized double-blinded treatment with lebrikizumab (n = 31) or placebo (n = 33). The pre-specified primary end-point was relative change in airway subepithelial eosinophils per mm
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/mm
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 neutralization of IL-13 may reduce asthmatic airway remodelling.
CLINICAL TRIAL REGISTRATION
NCT02099656.
Identifiants
pubmed: 32909660
doi: 10.1111/cea.13731
pmc: PMC7756263
doi:
Substances chimiques
Anti-Asthmatic Agents
0
Antibodies, Monoclonal
0
IL13 protein, human
0
Interleukin-13
0
lebrikizumab
U9JLP7V031
Banques de données
ClinicalTrials.gov
['NCT02099656']
Types de publication
Clinical Trial, Phase II
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1342-1351Informations de copyright
© 2020 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.
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