Predicting response to benralizumab in chronic obstructive pulmonary disease: analyses of GALATHEA and TERRANOVA studies.
Adult
Aged
Aged, 80 and over
Anti-Asthmatic Agents
/ therapeutic use
Antibodies, Monoclonal, Humanized
/ therapeutic use
Biomarkers
/ blood
Clinical Trials, Phase III as Topic
Disease Progression
Double-Blind Method
Drug Therapy, Combination
Eosinophils
Female
Forced Expiratory Volume
Humans
Leukocyte Count
Male
Middle Aged
Predictive Value of Tests
Pulmonary Disease, Chronic Obstructive
/ blood
Randomized Controlled Trials as Topic
Treatment Outcome
Journal
The Lancet. Respiratory medicine
ISSN: 2213-2619
Titre abrégé: Lancet Respir Med
Pays: England
ID NLM: 101605555
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
31
07
2019
revised:
12
09
2019
accepted:
12
09
2019
pubmed:
3
10
2019
medline:
25
8
2020
entrez:
3
10
2019
Statut:
ppublish
Résumé
Benralizumab did not significantly reduce exacerbations compared with placebo in the phase 3 GALATHEA and TERRANOVA trials of benralizumab for patients with chronic obstructive pulmonary disease (COPD). We aimed to identify clinical and physiological characteristics of patients with COPD that could help to identify people who are likely to have the greatest treatment effect with benralizumab. We analysed individual study and pooled results from GALATHEA and TERRANOVA. At study enrolment, patients from GALATHEA and TERRANOVA were aged 40-85 years, had moderate to very severe airflow limitation, had elevated blood eosinophil counts, and at least two exacerbations or one severe exacerbation in the previous year despite dual inhaled therapy (inhaled corticosteroids plus long-acting β For 2665 patients with elevated blood eosinophil counts, treatment effect with benralizumab every 8 weeks at 100 mg, but not at 30 mg, occurred for patients with a history of more frequent exacerbations, poorer baseline lung function, or greater baseline lung function improvement with short-acting bronchodilators. Patients with baseline blood eosinophil counts of 220 cells per μL or greater with: three or more exacerbations in the previous year receiving benralizumab every 8 weeks versus placebo, had rate ratios (RRs) of 0·69 (95% CI 0·56-0·83) for 100 mg and 0·86 (0·71-1·04) for 30 mg; postbronchodilator FEV Elevated blood eosinophil counts combined with clinical characteristics identified a subpopulation of patients with COPD who had reductions in exacerbations with benralizumab treatment. These hypothesis-generating analyses identified the potential efficacy of benralizumab 100 mg for this subpopulation. These findings require prospective evaluation in clinical trials. AstraZeneca.
Sections du résumé
BACKGROUND
Benralizumab did not significantly reduce exacerbations compared with placebo in the phase 3 GALATHEA and TERRANOVA trials of benralizumab for patients with chronic obstructive pulmonary disease (COPD). We aimed to identify clinical and physiological characteristics of patients with COPD that could help to identify people who are likely to have the greatest treatment effect with benralizumab.
METHODS
We analysed individual study and pooled results from GALATHEA and TERRANOVA. At study enrolment, patients from GALATHEA and TERRANOVA were aged 40-85 years, had moderate to very severe airflow limitation, had elevated blood eosinophil counts, and at least two exacerbations or one severe exacerbation in the previous year despite dual inhaled therapy (inhaled corticosteroids plus long-acting β
FINDINGS
For 2665 patients with elevated blood eosinophil counts, treatment effect with benralizumab every 8 weeks at 100 mg, but not at 30 mg, occurred for patients with a history of more frequent exacerbations, poorer baseline lung function, or greater baseline lung function improvement with short-acting bronchodilators. Patients with baseline blood eosinophil counts of 220 cells per μL or greater with: three or more exacerbations in the previous year receiving benralizumab every 8 weeks versus placebo, had rate ratios (RRs) of 0·69 (95% CI 0·56-0·83) for 100 mg and 0·86 (0·71-1·04) for 30 mg; postbronchodilator FEV
INTERPRETATION
Elevated blood eosinophil counts combined with clinical characteristics identified a subpopulation of patients with COPD who had reductions in exacerbations with benralizumab treatment. These hypothesis-generating analyses identified the potential efficacy of benralizumab 100 mg for this subpopulation. These findings require prospective evaluation in clinical trials.
FUNDING
AstraZeneca.
Identifiants
pubmed: 31575508
pii: S2213-2600(19)30338-8
doi: 10.1016/S2213-2600(19)30338-8
pii:
doi:
Substances chimiques
Anti-Asthmatic Agents
0
Antibodies, Monoclonal, Humanized
0
Biomarkers
0
benralizumab
71492GE1FX
Banques de données
ClinicalTrials.gov
['NCT02138916', 'NCT02155660']
Types de publication
Evaluation Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
158-170Subventions
Organisme : Department of Health
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.