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

Abstract

INTRODUCTION\nImproved 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.\n\n\nMATERIALS AND METHODS\nUsing 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\u202fcells/μL at screening or ≥300\u202fcell/μL in the 12 months prior to study), were treated with mepolizumab, and provided consent for genetic analysis.\n\n\nRESULTS\nFrom 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\u202f=\u202f5\u202f×\u202f10-8).\n\n\nCONCLUSIONS\nIn this exploratory study in patients with COPD, with peripheral blood eosinophilia, no genetic effects on mepolizumab-treatment response were identified.