No genetic association detected with mepolizumab efficacy in severe asthma

Lynn Condreay, Mathias Chiano, Hector Ortega, Natalie Buchan, Elizabeth Harris, Eugene R. Bleecker, Philip J. Thompson, Marc Humbert, Peter Gibson, Steven Yancey, Soumitra Ghosh

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background and objectives Treatment with mepolizumab, a humanized monoclonal antibody to interleukin-5, reduces the rate of asthma exacerbations and the requirement for systemic glucocorticoids while maintaining asthma control. Treatment decisions are guided by predictors of response, including blood eosinophil thresholds in patients with frequent exacerbations despite intensive anti-inflammatory and controller treatment. Identification of additional predictors of response could aid treatment decisions. We investigated genetic associations that may predict response to mepolizumab-treatment. Methods In this post hoc analysis of DREAM and MENSA, association of genetic markers was tested in patients with severe asthma treated with mepolizumab who provided consent for pharmacogenetic research. Association was tested in a tiered approach with alpha spend differing for candidate genetic markers selected for prior history of association with relevant traits or pathways and in a genome-wide analyses (p < 4.7 × 10−4 and p < 5 × 10−8, respectively). Efficacy endpoints included: clinically significant exacerbation rate (tested using a negative binomial model), time to first exacerbation (tested with a Cox proportional hazards model), change in exacerbation rate, change in eosinophil count, and change in IgE level (tested by linear regression). Results No genetic marker was significantly associated with the primary endpoint, clinically significant exacerbation rate. One genetic marker was associated with time to first clinically significant exacerbation, but this association was driven by the DREAM data and was not supported in additional sensitivity analyses by treatment regimen/dose. Conclusion No genetic effect on mepolizumab-treatment response was identified in this population on intensive asthma treatment, with history of frequent exacerbations and pre-selected for airway eosinophilia.

Original languageEnglish
Pages (from-to)178-180
Number of pages3
JournalRespiratory Medicine
Volume132
DOIs
Publication statusPublished - 1 Nov 2017

    Fingerprint

Cite this

Condreay, L., Chiano, M., Ortega, H., Buchan, N., Harris, E., Bleecker, E. R., ... Ghosh, S. (2017). No genetic association detected with mepolizumab efficacy in severe asthma. Respiratory Medicine, 132, 178-180. https://doi.org/10.1016/j.rmed.2017.10.019