Effect of Benralizumab treatment related immune modulation on COPD airway microbiome

<bold>Background:</bold> Chronic obstructive pulmonary disease (COPD) predominantly represents a neutrophilic inflammatory phenotype, however 1/3 of the cases are eosinophilic. Benralizumab is an afucosylated humanised monoclonal antibody that targets the IL-5 receptor α subunit, leading to rapid and near-complete eosinophil depletion via antibody-dependent cellular cytotoxicity. We investigated the relationship of COPD airway microbiome in response to benralizumab targeted immune modulation. <bold>Methods:</bold> Sputum samples from 94 COPD patients enrolled to the GALATHEA trial (<ext-link>NCT02138916</ext-link>) and randomized to receive placebo (33), benralizumab at 100mg (29) or 30mg (32) over 52 weeks, were analysed at baseline, week 24 and at end-of-treatment (week 56). Sputum microbiota taxonomic profiles and diversity indices, generated from paired-end Illumina sequencing targeting the 16sRNA gene, were used to perform the airway microbiome comparisons. Linear mixed model analysis was applied to assess the eosinophil-related immune marker changes. <bold>Results:</bold> Participants treated with 100 and 30 mg benralizumab respectively, showed a significant reduction from baseline in blood and sputum eosinophil counts (Blood p = 1.2E-10 & p = 8.8E-10; Sputum p=0.03 & p = 0.004) and eosinophil-derived mediators (ECP p < 3E-09 & p < 2E-08; EDN p < 8E- 12 & p < 2E-09). However, no significant changes in the composition or diversity of the sputum microbiome was observed. <bold>Conclusions:</bold> In this study, the airway microbiome was unaffected by targeted reduction of eosinophilic inflammation with benralizumab treatment.