International Journal of COPD (Apr 2018)
Exacerbation heterogeneity in COPD: subgroup analyses from the FLAME study
Abstract
Claus F Vogelmeier,1 Kenneth R Chapman,2 Marc Miravitlles,3 Nicolas Roche,4 Jørgen Vestbo,5 Chau Thach,6 Donald Banerji,6 Robert Fogel,6 Francesco Patalano,7 Petter Olsson,8 Konstantinos Kostikas,7 Jadwiga A Wedzicha9 1Member of the German Center for Lung Research (DZL), Department of Medicine, Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, Philipps-Universität Marburg, Marburg, Germany; 2Asthma and Airway Centre, University Health Network and University of Toronto, Toronto, ON, Canada; 3Pneumology Department, Hospital Universitari Vall d’Hebron, CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, Spain; 4Service de Pneumologie AP-HP, Cochin Hospital, University Paris Descartes (EA2511), Paris, France; 5Institute of Infection, Immunity and Respiratory Medicine, The University of Manchester and Manchester University NHS Foundation Trust, Manchester, UK; 6Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 7Novartis Pharma AG, Basel, Switzerland; 8Novartis Sverige AB, Täby, Sweden; 9National Heart and Lung Institute, Imperial College London, London, UK Background: The FLAME study compared once-daily indacaterol/glycopyrronium (IND/GLY) 110/50 µg with twice-daily salmeterol/fluticasone (SFC) 50/500 µg in symptomatic patients with moderate to very severe COPD and a history of exacerbations in the previous year. Methods: This prespecified and post hoc subgroup analysis evaluated treatment efficacy on 1) moderate/severe exacerbations according to prior exacerbation history and treatment, and 2) types of exacerbations according to health care resource utilization (HCRU) during 1-year follow-up. Results: IND/GLY reduced the rate of moderate/severe exacerbations versus SFC in patients with a history of 1 exacerbation (rate ratio [RR]: 0.83, 95% CI: 0.75–0.93), ≥2 exacerbations (RR: 0.85, 95% CI: 0.70–1.03) and ≥2 exacerbations or ≥1 hospitalization in the previous year (RR: 0.86, 95% CI: 0.74–1.00). Prolonged time-to-first exacerbation was observed in all the groups according to exacerbation history. Moderate/severe exacerbations decreased with IND/GLY versus SFC, independent of previous treatment. IND/GLY significantly reduced rates of moderate/severe exacerbations treated with antibiotics (RR: 0.79, 95% CI: 0.67–0.93) and systemic corticosteroids and antibiotics (RR: 0.80, 95% CI: 0.70–0.91); rates of exacerbations treated with systemic corticosteroids alone were comparable (RR: 0.99, 95% CI: 0.80–1.22). Conclusion: Overall, IND/GLY demonstrated consistent beneficial effects versus SFC on moderate/severe exacerbations, independent of prior exacerbation history or treatment. The efficacy of IND/GLY on exacerbation prevention was superior to SFC for exacerbations treated with antibiotics with/without systemic corticosteroids and was similar for exacerbations treated with systemic corticosteroids alone. Keywords: indacaterol/glycopyrronium, salmeterol/fluticasone, LABA/LAMA, LABA/ICS