Once-Daily Triple Therapy in Patients with COPD: Patient-Reported Symptoms and Quality of Life

Abstract

Introduction: Directly recorded patient experience of symptoms and health-related quality of life (HRQoL) can complement lung function and exacerbation rate data in chronic obstructive pulmonary disease (COPD) clinical studies. The FULFIL study recorded daily symptoms and activity limitation together with additional patient-reported outcomes of dyspnea and HRQoL, as part of the prespecified analyses. FULFIL co-primary endpoint data have been previously reported.

Methods: FULFIL was a phase III, 24-week, randomized, double-blind, double-dummy, multicenter study comparing once-daily single inhaler triple therapy [fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI)] 100 µg/62.5 µg/25 µg with twice-daily inhaled corticosteroid/long-acting β2-agonist therapy [budesonide/formoterol (BUD/FOR)] 400 µg/12 µg in patients with symptomatic COPD at risk of exacerbations. A subset participated for 52 weeks. Patient-reported assessments were: Evaluating Respiratory Symptoms in COPD™ (E-RS: COPD), St George's Respiratory Questionnaire (SGRQ) for COPD, COPD Assessment Test (CAT), baseline and transitional dyspnea indices (TDI) and daily and global anchor questions for activity limitation.

Results: FF/UMEC/VI showed greater reductions from baseline in 4-weekly mean E-RS: COPD total and all subscale scores compared with BUD/FOR; differences were statistically significant (P < 0.05) at each time period. FF/UMEC/VI also demonstrated greater improvements from baseline at weeks 4 and 24 in SGRQ domain scores and TDI focal score compared with BUD/FOR. At weeks 4 and 24, improvements greater than the minimal clinically important difference from baseline were observed in CAT score with FF/UMEC/VI, but not BUD/FOR; differences were statistically significant (P ≤ 0.003).

Conclusion: These findings demonstrate sustained daily symptom and HRQoL benefits of FF/UMEC/VI versus BUD/FOR. The inclusion of the CAT may provide data that are readily generalizable to everyday clinical practice.

Trial registration: ClinicalTrials.gov number: NCT02345161.

Funding: GSK.

Keywords: Budesonide/formoterol; COPD burden; Fluticasone furoate/umeclidinium/vilanterol; Patient-reported outcomes; Respiratory; Symptom burden.

Figures

Fig. 1

CONSORT flow chart for the FULFIL study. BUD/FOR budesonide/formoterol, FF/UMEC/VI fluticasone furoate/umeclidinium/vilanterol, ITT intent-to-treat

Fig. 2

Mean change from baseline in 4-weekly E-RS: COPD scores (ITT): total score (a); breathlessness (b); cough and sputum (c); chest symptoms (d). Dark dotted lines represent baseline and light dotted lines represent response threshold. BUD/FOR budesonide/formoterol, CI confidence interval, E-RS: COPD Evaluating Respiratory Symptoms in COPD, FF/UMEC/VI fluticasone furoate/umeclidinium/vilanterol, ITT intent-to-treat, LS least squares

Fig. 3

Mean change in baseline in CAT score in the ITT population. BUD/FOR budesonide/formoterol, CAT COPD Assessment Test, CI confidence interval, FF/UMEC/VI fluticasone furoate/umeclidinium/vilanterol, ITT intent-to-treat, LS least squares, SE standard error

Fig. 4

Mean change from baseline in SGRQ domain scores in the ITT population. Treatment differences (95% CIs) shown. *P < 0.05; **P < 0.01; ***P < 0.001. BUD/FOR budesonide/formoterol, CI confidence interval, FF/UMEC/VI fluticasone furoate/umeclidinium/vilanterol, ITT intent-to-treat, LS least squares, SGRQ St George’s Respiratory Questionnaire

Fig. 5

Change from baseline in CAT score versus change from baseline in SGRQ total score at week 24 in the ITT population. Line represents line of best fit. Fitted regression line using the SAS procedure SGPLOT with a REG statement. BUD/FOR budesonide/formoterol, CAT COPD Assessment Test, FF/UMEC/VI fluticasone furoate/umeclidinium/vilanterol, ITT intent-to-treat, SGRQ St George’s Respiratory Questionnaire