Blood Eosinophils: A Biomarker of Response to Extrafine Beclomethasone/Formoterol in Chronic Obstructive Pulmonary Disease

Abstract

Rationale. Blood eosinophilia has been shown to be associated with a significant proportion \nof COPD exacerbations and stratifies the clinical response to systemic corticosteroids. The \nFORWARD study was a randomised, double-blind, parallel group trial that compared 48 \nweeks treatment with extrafine beclomethasone dipropionate plus formoterol fumarate \n(BDP/FF) vs. FF, in severe COPD patients with a history of exacerbations. Objectives. We \nhypothesised that there would be treatment differences in response to BDP/FF when \nstratifying by baseline blood eosinophil count in a post hoc analysis. Methods. The patients \n(N=1,184) were stratified into four quartile groups based on the baseline eosinophil count and \nanalyses on exacerbation rate, change in pre dose FEV1 and St. George’s Respiratory \nQuestionnaire [SGRQ] total score over 48 weeks were performed across these. A predictive \nmodel of future exacerbations was developed based upon baseline blood eosinophil count and \nother factors. Results. The adjusted treatment difference over 48 weeks between the BDP/FF \nand FF groups was largest within the highest baseline blood eosinophil quartile (≥279.8/µl \n/µl). Within this quartile a significant (i) 46% reduction in exacerbation rate, (ii) 0.102 L \nimprovement in pre bronchodilator FEV1 and (iii) 5.9 units improvement in SGRQ total score \nwere seen in favour of BDP/FF. Predictive modelling suggested that the risk of exacerbations \nwas influenced by baseline blood eosinophils in patients treated with FF alone, but not in \npatients treated with BDP/FF. Conclusions. The presence of a significant blood eosinophilia \nseems to be associated with a particularly favorable response to ICS/LABA therapy in COPD \npatients.