Blood Eosinophils and Response to Maintenance Chronic Obstructive Pulmonary Disease Treatment. Data from the FLAME Trial.

Abstract

Post hoc analyses suggest that blood eosinophils have potential as a predictive biomarker of inhaled corticosteroid efficacy in the management of chronic obstructive pulmonary disease (COPD). We prospectively investigated the value of blood eosinophils as a predictor of responsiveness to an inhaled corticosteroid/long-acting β₂-agonist combination versus a long-acting β₂-agonist/long-acting muscarinic antagonist combination for exacerbation prevention. We conducted prespecified analyses of data from the FLAME (Effect of Indacaterol Glycopyronium vs Fluticasone Salmeterol on COPD Exacerbations) study, which compared once-daily long-acting β₂-agonist/long-acting muscarinic antagonist indacaterol/glycopyrronium 110/50 μg with twice-daily long-acting β₂-agonist/inhaled corticosteroid salmeterol/fluticasone combination 50/500 μg in patients with one or more exacerbations in the preceding year. Subsequent post hoc analyses were conducted to address further cutoffs and endpoints. We compared treatment efficacy according to blood eosinophil percentage (<2% and ≥2%, <3% and ≥3%, and <5% and ≥5%) and absolute blood eosinophil count (<150 cells/μl, 150 to <300 cells/μl, and ≥300 cells/μl). Indacaterol/glycopyrronium was significantly superior to salmeterol/fluticasone for the prevention of exacerbations (all severities, or moderate or severe) in the <2%, ≥2%, <3%, <5%, and <150 cells/μl subgroups, and at no cutoff was salmeterol/fluticasone superior to indacaterol/glycopyrronium. Furthermore, the rate of moderate or severe exacerbations did not increase with increasing blood eosinophils. The incidence of pneumonia was higher in patients receiving salmeterol/fluticasone than indacaterol/glycopyrronium in both the <2% and ≥2% subgroups. Our prospective analyses indicate that indacaterol/glycopyrronium provides superior or similar benefits over salmeterol/fluticasone regardless of blood eosinophil levels in patients with COPD. Clinical trial registered with www.clinicaltrials.gov (NCT01782326).