Fluticasone propionate/formoterol for COPD management: a randomized controlled trial

Abstract

Purpose

To evaluate fluticasone propionate/formoterol (FP/FORM) in COPD.

Patients and methods

COPD patients with forced expiratory volume in 1 s (FEV₁) ≤50% predicted and ≥1 moderate/severe COPD exacerbation in the last 12 months were randomized to FP/FORM 500/20 or 250/10 µg bid, or formoterol (FORM) 12 µg bid for 52 weeks. The primary outcome was the annualized rate of moderate/severe COPD exacerbations.

Results

In total, 1,765 patients were randomized. There were fewer discontinuations with FP/FORM 500/20 µg (20.6%) and 250/10 µg (24.0%) compared with FORM (26.1%). None of the two FP/FORM doses reduced the moderate/severe exacerbation rate versus FORM (rate ratios [RR]: 0.93; P≤0.402). There was a trend toward a lower moderate/severe exacerbation rate with FP/FORM 500/20 µg versus FORM in patients with ≥2 exacerbations in the preceding year (RR: 0.79; P=0.084). Pre- and post-dose FEV₁ and forced vital capacity were greater with FP/FORM 500/20 µg versus FORM (P≤0.039). There was a trend toward a lower EXAcerbations of Chronic pulmonary disease Tool (EXACT) exacerbation rate with FP/FORM 500/20 µg versus FORM (RR: 0.87; P=0.077). There were more St George’s Respiratory Questionnaire for COPD (SGRQ-C) responders with FP/FORM 500/20 µg than FORM (odds ratios [OR] at weeks 6, 23 and 52 ≥1.28; P≤0.054). EXACT-respiratory symptoms total and breathlessness scores were lower with both FP/FORM 500/20 µg and 250/10 µg versus FORM (P≤0.066). Acute β₂-agonist-induced effects and 24-hour Holter findings were similar for all treatments. Mean 24-hour urinary cortisol was similarly reduced with both FP/FORM doses. Radiologically confirmed pneumonia was seen in 2.4%, 3.2% and 1.5% of FP/FORM 500/20 µg, FP/FORM 250/10 µg and FORM-treated patients, respectively. Adverse events were otherwise similar across treatment groups.

Conclusion

FP/FORM did not reduce exacerbation rates versus FORM. Numerical benefits were observed with FP/FORM 500/20 µg versus FORM for secondary variables, including lung function, EXACT exacerbations, SGRQ-C and EXACT-respiratory symptoms total and breathlessness scores. Few efficacy differences were evident between FP/FORM 250/10 µg and FORM. Pneumonia was more frequent in FP/FORM-treated patients, although the absolute difference was low. Adverse events were otherwise similar between treatments.

Keywords:

• flutiform
• chronic bronchitis
• emphysema
• exacerbations
• eosinophils

Acknowledgments

The authors wish to thank all patients, investigators, sites, contract research organization staff and sponsor staff for their involvement in the study. Flutiform is a registered trade mark of Jagotec AG. Atimos and Modulite are registered trademarks of Chiesi Farmaceutici S.p.A. Spiriva is a registered trademark of Boehringer Ingelheim Pharma GmbH & Co. KG.

The study was funded by Mundipharma Research Limited. Editorial assistance to prepare this manuscript was provided by MD Medical Communications Limited, and was funded by Mundipharma Research Limited.

Author contributions

All authors reviewed this manuscript, take responsibility for the integrity of the data herein, drafting and revising the paper, meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship and have given final approval to the version to be published.

Disclosure

Professor Papi reports grants, personal fees, non-financial support and other from Chiesi, AstraZeneca, GlaxoSmithKline, Boehringer Ingelheim, Merck Sharp & Dohme, Pfizer, Takeda, Mundipharma, TEVA; personal fees and non-financial support from Menarini, Novartis, Zambon; and grants from Sanofi, outside the submitted work. Dr Koroknai is an employee of PAREXEL, the contract research organization contracted to perform the study. Ms McAulay, Dr Dalvi and Dr Overend are employees of Mundipharma Research Limited, Cambridge, UK. Dr Mersmann is an employee of Mundipharma Research GmbH & Co. KG, Germany. Professor Dokic, Dr Tzimas, Dr Mészáros, and Dr Olech-Cudzik have no conflicts of interest to declare. The authors report no other conflicts of interest in this work.