Exacerbation heterogeneity in COPD: subgroup analyses from the FLAME study

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:

• indacaterol/glycopyrronium
• salmeterol/fluticasone
• LABA/LAMA
• LABA/ICS

Acknowledgments

The FLAME study was sponsored by Novartis Pharma AG. The authors would like to thank patients and staff at the participating centers. The authors also thank Sinéad Flannery, Chiranjit Ghosh and Santanu Sannigrahi (professional medical writers; Novartis) for assistance in the preparation of this manuscript. Writing support was funded by the study sponsor. All the authors vouch for the accuracy and completeness of the data.

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.

Author contributions

JAW, CV, KRC, MM, NR, JV, CT, DB, RF, FP, PO and KK all made substantial contributions to the conception and design of the analysis, and interpretation of data. All authors contributed toward data analysis, drafting and revising the paper and agree to be accountable for all aspects of the work. All authors provided their final approval to the version to be published. The authors are accountable for the accuracy and integrity of this work.