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Clinical Trial
. 2018 Apr 10:13:1125-1134.
doi: 10.2147/COPD.S160011. eCollection 2018.

Exacerbation heterogeneity in COPD: subgroup analyses from the FLAME study

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 Wedzicha  9
Affiliations
Clinical Trial

Exacerbation heterogeneity in COPD: subgroup analyses from the FLAME study

Claus F Vogelmeier et al. Int J Chron Obstruct Pulmon Dis. .

Abstract

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: LABA/ICS; LABA/LAMA; indacaterol/glycopyrronium; salmeterol/fluticasone.

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Conflict of interest statement

Disclosure CFV has received grant funding, honoraria for lectures and/or 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.

Figures

Figure 1
Figure 1
Annualized rate of moderate or severe COPD exacerbations in different subgroups of patients based on prior exacerbations (full analysis set). Abbreviations: IND/GLY, indacaterol/glycopyrronium; SFC, salmeterol/fluticasone.
Figure 2
Figure 2
Kaplan–Meier plot of time to first moderate or severe COPD exacerbation in different subgroups of patients based on prior exacerbations (full analysis set). Notes: (A) Patients with history of 1 exacerbation in the previous year. (B) Patients with history of ≥2 exacerbations in the previous year. (C) Patients with history of ≥2 exacerbations or at least 1 exacerbation that led to hospitalization in the previous year. Abbreviations: IND/GLY, indacaterol/glycopyrronium; SFC, salmeterol/fluticasone.
Figure 3
Figure 3
Annualized rate of moderate or severe COPD exacerbations based on previous treatment (full analysis set). Abbreviations: ICS, inhaled corticosteroid; IND/GLY, indacaterol/glycopyrronium; LABA, long-acting β2 agonist; LAMA, long-acting muscarinic antagonist; SFC, salmeterol/fluticasone.
Figure 4
Figure 4
Number and RR of moderate or severe COPD exacerbations according to HCRU with IND/GLY versus SFC during the treatment period. Notes: *If an exacerbation satisfies multiple criteria (eg, required treatment with a medication and later required hospitalization), then the event is counted in each category (row) satisfied. Thus, the percentages do not add up to 100%. Abbreviations: HCRU, health care resource utilization; IND/GLY, indacaterol/glycopyrronium; RR, rate ratio; SFC, salmeterol/fluticasone.
See this image and copyright information in PMC

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