Abstract
Background: Benralizumab depletes eosinophils and basophils by enhanced antibody-dependent cell-mediated cytotoxicity, and has demonstrated efficacy for pts with moderate to severe asthma or COPD with eosinophilic inflammation.1,2
Objectives: We investigated effects of 100-mg benralizumab on blood inflammatory markers by proteomic and gene-expression analyses.
Methods: Serum samples for proteomic analysis and whole blood PAXgene tubes for gene expression analysis were collected pre- and 32 or 52 weeks post-treatment in the asthma and COPD studies. Proteomic analyses were conducted on a custom set of Rules-Based Medicine analytes (90 for asthma, 147 for COPD). Gene expression was profiled by Affymetrix HGU133 plus 2 arrays (∼54K probes). Transcriptomic activity of immune signatures was determined via gene set variation analysis (GSVA). Treatment-related differences between genes, analytes, and gene signatures were determined by t-test.
Results: Eosinophil chemokines CCL11 and CCL24 alone were up-regulated (p<0.05) by benralizumab: by 2- and 1.3-fold in the asthma and 2.6- and 1.6-fold in the COPD studies. Genes decreased by benralizumab (FDR<0.05) included eosinophil or basophil markers (CLC, PRSS33, IL5RA, CCR3, IDO1, OLIG1); immune-signaling complex genes (FCER1A); G-protein-coupled receptor genes (HRH4, ADORA3, P2RY14); and other immune-related genes (ALOX15 and OLIG2). GSVA on immune signatures indicated significant treatment reductions (p<0.05) in eosinophil-associated signatures. Other cell signatures were not altered.
Conclusion: Benralizumab is highly selective, modulating proteins or genes associated with eosinophils or basophils.
1Lancet Respir Med. 2014;2:878–90.
2Lancet Respir Med. 2014;2:891-901.
- Copyright ©the authors 2016