24-Hour Serial Spirometric Assessment of Once-Daily Fluticasone Furoate/Umeclidinium/Vilanterol Versus Twice-Daily Budesonide/Formoterol in Patients with COPD: Analysis of the FULFIL Study

David A Lipson, Ruby Birk, Noushin Brealey, Chang-Qing Zhu, David A Lipson, Ruby Birk, Noushin Brealey, Chang-Qing Zhu

Abstract

Introduction: Few studies have utilized 24-h serial spirometry to compare the effects of inhaled chronic obstructive pulmonary disease (COPD) therapies on lung function. The FULFIL study previously reported significant lung function improvements with once-daily single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus twice-daily single-inhaler budesonide/formoterol (BUD/FOR) in patients with symptomatic COPD at risk of exacerbations.

Methods: This prespecified analysis evaluated 24-h serial spirometry data from a subgroup of 406 patients in FULFIL. BUD/FOR twice-daily dosing was maintained during 24-h spirometry. A post hoc analysis evaluated serial forced expiratory volume in 1 s (FEV1) at day 1 and week 24 by disease severity at screening (FEV1 < 50% predicted and no moderate or severe exacerbation in prior year, FEV1 < 50% predicted and ≥ 1 moderate or severe exacerbation in prior year, and FEV1 ≥ 50% and < 80% predicted and ≥ 2 moderate or ≥ 1 severe exacerbations in prior year).

Results: Odds of achieving a ≥ 100-mL increase from baseline in FEV1 within the first 6 h post dose on day 1 were significantly greater with FF/UMEC/VI than BUD/FOR [odds ratio 2.79 (95% confidence interval 1.56-4.98); p < 0.001]. FF/UMEC/VI led to greater improvements in weighted mean FEV1 over 0-6, 0-12, 0-24, and 12-24 h on day 1 and at week 24, with the greatest between-group differences at week 24 (range 196-210 mL; all p < 0.001). Significant between-treatment differences in FEV1 and forced vital capacity (FVC) in favor of FF/UMEC/VI versus BUD/FOR were seen at all time points at week 24 (FEV1 range 156-231 mL, all p < 0.001; FVC range 139-309 mL, all p ≤ 0.002). Serial FEV1 results were consistent irrespective of disease severity at screening.

Conclusion: These findings further demonstrate sustained lung function benefits with once-daily FF/UMEC/VI single-inhaler triple therapy in patients with symptomatic COPD at risk of exacerbations across a range of disease severities.

Trial registration: ClinicalTrials.gov NCT02345161.

Keywords: Chronic obstructive pulmonary disease; Inhaled corticosteroid; Long-acting muscarinic antagonist; Long-acting β2-agonist; Lung function; Serial FEV1; Single-inhaler triple therapy.

Figures

Fig. 1
Fig. 1
Increase of ≥ 100 mL over baseline in FEV1 0–6 h post dose on day 1. BUD budesonide, FEV1 forced expiratory volume in 1 s, FF fluticasone furoate, FOR formoterol, UMEC umeclidinium, VI vilanterol
Fig. 2
Fig. 2
LS mean change from baseline in FEV1 over 24 h on day 1 (a) and at week 24 (b). First doses of FF/UMEC/VI and BUD/FOR given at 0 h; second dose of BUD/FOR given approx. 12 h later. *p < 0.05 and #p < 0.001 for comparison with BUD/FOR. BUD budesonide, CI confidence interval, FEV1 forced expiratory volume in 1 s, FF fluticasone furoate, FOR formoterol, LS least squares, UMEC umeclidinium, VI vilanterol. Figure reproduced with permission from the authors (David A. Lipson, et al. Am J Respir Crit Care Med. 2017;195:A3605)
Fig. 3
Fig. 3
LS mean change from baseline in FEV1 over 24 h on day 1 by disease severity at screening. First doses of FF/UMEC/VI and BUD/FOR given at 0 h; second dose of BUD/FOR given approx. 12 h later. *p < 0.05 and #p < 0.001 for comparison with BUD/FOR. BUD budesonide, CI confidence interval, FEV1 forced expiratory volume in 1 s, FF fluticasone furoate, FOR formoterol, LS least squares, UMEC umeclidinium, VI vilanterol
Fig. 4
Fig. 4
LS mean change from baseline in FEV1 over 24 h at week 24 by disease severity at screening. First doses of FF/UMEC/VI and BUD/FOR given at 0 h; second dose of BUD/FOR given approx. 12 h later. *p < 0.05 and #p < 0.001 for comparison with BUD/FOR. BUD budesonide, CI confidence interval, FEV1 forced expiratory volume in 1 s, FF fluticasone furoate, FOR formoterol, LS least squares, UMEC umeclidinium, VI vilanterol
Fig. 5
Fig. 5
LS mean change from baseline in FVC over 24 h on day 1 (a) and at week 24 (b). First doses of FF/UMEC/VI and BUD/FOR given at 0 h; second dose of BUD/FOR given approx. 12 h later. *p < 0.05 and #p ≤ 0.001 for comparison with BUD/FOR. BUD budesonide, CI confidence interval, FVC forced vital capacity, FF fluticasone furoate, FOR formoterol, LS least squares, UMEC umeclidinium, VI vilanterol

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