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 beta2-agonist combination versus a long-acting beta2-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 beta2-agonist/long-acting muscarinic antagonist indacaterol/glycopyrronium 110/50 mug with twice-daily long-acting beta2-agonist/inhaled corticosteroid salmeterol/fluticasone combination 50/500 mug 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/mul, 150 to <300 cells/mul, and >/=300 cells/mul). 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/mul 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. Clinical trial registered with
- Roche, N.
- Chapman, K. R.
- Vogelmeier, C. F.
- Herth, F. J. F.
- Thach, C.
- Fogel, R.
- Olsson, P.
- Patalano, F.
- Banerji, D.
- Wedzicha, J. A.
Keywords
- Adrenal Cortex Hormones/administration & dosage/therapeutic use
- Adrenergic beta-2 Receptor Agonists/administration & dosage/therapeutic use
- Aged
- Biomarkers/blood
- Double-Blind Method
- Drug Therapy, Combination
- *Eosinophils/drug effects
- Female
- Fluticasone-Salmeterol Drug Combination/therapeutic use
- Humans
- Indans/therapeutic use
- Leukocyte Count
- Male
- Middle Aged
- Pulmonary Disease, Chronic Obstructive/*blood/drug therapy
- Quinolones/therapeutic use
- Treatment Outcome
- *qva149
- *bronchodilation
- *chronic obstructive pulmonary disease
- *exacerbations
- *inhaled corticosteroids