No genetic associations with mepolizumab efficacy in COPD with peripheral blood eosinophilia.
Respir Med
; 155: 26-28, 2019 08.
Article
em En
| MEDLINE
| ID: mdl-31295674
ABSTRACT
INTRODUCTION:
Improved understanding of genetic effects on response to treatments with novel approaches for COPD with peripheral blood eosinophilia, such as mepolizumab (a humanized monoclonal antibody to IL-5), may improve treatment outcomes. We conducted a study to identify genetic variants associated with efficacy of mepolizumab COPD. MATERIALS ANDMETHODS:
Using generalized linear and logistic regression models, genome-wide association analyses were performed to investigate genetic associations with frequency of moderate and/or severe COPD exacerbations in COPD subjects receiving mepolizumab (weeks 0-52). Additional analyses included (i) frequency of COPD exacerbations requiring hospitalization or emergency department visit (weeks 0-52), (ii) change from baseline mean total St. George's Respiratory Questionnaire (SGRQ) score (week 24), and (iii) SGRQ response defined as achieving a 4 unit or greater decrease of SGRQ score from baseline (week 24). This study included 610 patients with COPD, a subset of the Intent-to-treat (ITT) populations in two phase III double-blind trials assessing the efficacy and safety of mepolizumab, METREX (NCT02105948) and METREO (NCT02105961). All subjects had elevated eosinophil levels (≥150â¯cells/µL at screening or ≥300â¯cell/µL in the 12 months prior to study), were treated with mepolizumab, and provided consent for genetic analysis.RESULTS:
From this post-hoc analysis, no genetic variant was significantly associated with moderate and/or severe COPD exacerbations or any of the other endpoints tested (threshold for statistical significance at the genome-wide level, pâ¯=â¯5â¯×â¯10-8).CONCLUSIONS:
In this exploratory study in patients with COPD, with peripheral blood eosinophilia, no genetic effects on mepolizumab-treatment response were identified.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença Pulmonar Obstrutiva Crônica
/
Eosinofilia
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Estudos de Associação Genética
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Anticorpos Monoclonais Humanizados
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
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Risk_factors_studies
Limite:
Aged
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Humans
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Middle aged
Idioma:
En
Revista:
Respir Med
Ano de publicação:
2019
Tipo de documento:
Article