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Respir Med. 2019 Aug;155:26-28. doi: 10.1016/j.rmed.2019.07.004. Epub 2019 Jul 5.

No genetic associations with mepolizumab efficacy in COPD with peripheral blood eosinophilia.

Author information

1
PAREXEL International, Durham, NC, USA. Electronic address: Lynn.Condreay@parexel.com.
2
PAREXEL International, Durham, NC, USA.
3
GlaxoSmithKline, Research Triangle Park, NC, USA.
4
GlaxoSmithKline, King of Prussia, PA, USA.

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 AND METHODS:

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 (≥150 cells/μL at screening or ≥300 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, p = 5 × 10-8).

CONCLUSIONS:

In this exploratory study in patients with COPD, with peripheral blood eosinophilia, no genetic effects on mepolizumab-treatment response were identified.

KEYWORDS:

COPD; Eosinophilia; Exacerbation; Mepolizumab; Pharmacogenetics; SGRQ

PMID:
31295674
DOI:
10.1016/j.rmed.2019.07.004

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