Modulation of inflammation by benralizumab in eosinophilic airway disease

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 p Conclusion: Benralizumab is highly selective, modulating proteins or genes associated with eosinophils or basophils. 1 Lancet Respir Med . 2014;2:878–90. 2 Lancet Respir Med . 2014;2:891-901.