Background: The FLAME study compared once-daily indacaterol/glycopyrronium (IND/GLY) 110/50 mug with twice-daily salmeterol/fluticasone (SFC) 50/500 mug 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.
- Vogelmeier, C. F.
- Chapman, K. R.
- Miravitlles, M.
- Roche, N.
- Vestbo, J.
- Thach, C.
- Banerji, D.
- Fogel, R.
- Patalano, F.
- Olsson, P.
- Kostikas, K.
- Wedzicha, J. A.
Keywords
- Adrenal Cortex Hormones/*administration & dosage/adverse effects
- Adrenergic beta-2 Receptor Agonists/*administration & dosage/adverse effects
- Aged
- Bronchodilator Agents/*administration & dosage/adverse effects
- Disease Progression
- Double-Blind Method
- Drug Administration Schedule
- Female
- Fluticasone-Salmeterol Drug Combination/*administration & dosage/adverse effects
- Forced Expiratory Volume
- Glycopyrrolate/*administration & dosage/adverse effects
- Hospitalization
- Humans
- Indans/*administration & dosage/adverse effects
- Kaplan-Meier Estimate
- Lung/*drug effects/physiopathology
- Male
- Middle Aged
- Muscarinic Antagonists/*administration & dosage/adverse effects
- Odds Ratio
- Proportional Hazards Models
- Pulmonary Disease, Chronic Obstructive/diagnosis/*drug therapy/physiopathology
- Quinolones/*administration & dosage/adverse effects
- Risk Factors
- Severity of Illness Index
- Time Factors
- Treatment Outcome
- Vital Capacity
- Laba/ics
- Laba/lama
- indacaterol/glycopyrronium
- salmeterol/fluticasone
- participation in advisory boards from AstraZeneca, Boehringer Ingelheim, CSL
- Behring, Chiesi, GSK, Grifols, Menarini, Mundipharma, Novartis, Teva, and Cipla.
- KRC reports grants and personal fees from AstraZeneca, grants and personal fees
- from Boehringer Ingelheim, grants from Baxter, grants and personal fees from CSL
- Behring, grants and personal fees from Grifols, grants from GlaxoSmithKline,
- grants and personal fees from Sanofi, grants and personal fees from Genentech,
- grants and personal fees from Kamada, grants from Amgen, grants and personal fees
- from Roche, grants and personal fees from Novartis, personal fees from Merck,
- personal fees from CIHR-GSK Research Chair in Respiratory Health Care Delivery,
- UHN, during the conduct of the study. NR has received grants and personal fees
- from Boehringer Ingelheim, Novartis, Pfizer
- personal fees from Teva, GSK,
- AstraZeneca, Chiesi, Mundipharma, Cipla, Sanofi, Sandoz, 3M, and Zambon, outside
- the submitted work. JV reports personal fees from GlaxoSmithKline, Chiesi
- pharmaceuticals, Boehringer-Ingelheim, Novartis, Almirall, AstraZeneca, Bioxydyn,
- Ferring, outside the submitted work. MM has received speaker fees from Boehringer
- Ingelheim, Chiesi, Cipla, Menarini, Grifols and Novartis, and consulting fees
- from Boehringer Ingelheim, GlaxoSmithKline, Gebro Pharma, CLS Behring, Novartis
- and Grifols. JAW reports grants from GSK, grants from Johnson and Johnson, other
- from Novartis, other from Boehringer Ingelheim, other from Astra Zeneca, other
- from GSK, grants from GSK, grants from Astra Zeneca, grants from Boehringer
- Ingelheim, grants from Novartis, outside the submitted work. CT, DB, RF, FP and
- KK are employees and shareholders of Novartis Pharma AG. PO is an employee of
- Novartis AB and a Novartis shareholder. The authors report no other conflicts of
- interest in this work.
