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

Rationale: 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). Objectives: We prospectively investigated the value of blood eosinophils as a predictor of responsiveness to an inhaled corticosteroid/long-acting beta(2)-agonist combination versus a long-acting beta(2)-agonist/long-acting muscarinic antagonist combination for exacerbation prevention. Methods: 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 beta(2)-agonist/long-acting muscarinic antagonist indacaterol/glycopyrronium 110/50 mg with twice-daily long-acting beta(2)-agonist/inhaled corticosteroid salmeterol/fluticasone combination 50/500 mu g in patients with one or more exacerbations in the preceding year. Subsequent post hoc analyses were conducted to address further cutoffs and endpoints. Measurements and Main Results: 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/mu l, 150 to <300 cells/mu l, and >= 300 cells/mu l). 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/mu l 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. Conclusions: Our prospective analyses indicate that indacaterol/glycopyrronium provides superior or similar benefits over salmeterol/fluticasone regardless of blood eosinophil levels in patients with COPD.