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

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