Single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) triple therapy versus tiotropium monotherapy in patients with COPD

Abstract

Chronic obstructive pulmonary disease (COPD) treatment guidelines do not currently include recommendations for escalation directly from monotherapy to triple therapy. This 12-week, double-blind, double-dummy study randomized 800 symptomatic moderate-to-very-severe COPD patients receiving tiotropium (TIO) for ≥3 months to once-daily fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 mcg via ELLIPTA (n = 400) or TIO 18 mcg via HandiHaler (n = 400) plus matched placebo. Study endpoints included change from baseline in trough forced expiratory volume in 1 s (FEV1) at Days 85 (primary), 28 and 84 (secondary), health status (St George's Respiratory Questionnaire [SGRQ] and COPD Assessment Test [CAT]) and safety. FF/UMEC/VI significantly improved trough FEV1 at all timepoints (Day 85 treatment difference [95% CI] 95 mL [62-128]; P < 0.001), and significantly improved SGRQ and CAT versus TIO. Treatment safety profiles were similar. Once-daily single-inhaler FF/UMEC/VI significantly improved lung function and health status versus once-daily TIO in symptomatic moderate-to-very-severe COPD patients, with a similar safety profile.

Trial registration: ClinicalTrials.gov NCT03474081.

Conflict of interest statement

S.B. has received speaker fees from GSK, Boehringer Ingelheim, Auris Health, Veran, Veracyte, Biodesix, Pinnacle Biologics, and Circulogene. He has also previously participated in speaker’s bureau for Sunovion Pharmaceuticals and holds stocks/shares in Veracyte. M.A. has received speaker fees from AstraZeneca, Boehringer Ingelheim, GSK, MEDA, Orion Pharma, and TEVA. A.A. has received consultancy fees from Boehringer Ingelheim, Novartis, AstraZeneca, and Theravance Mylan. N.B., C.C., T.C.C., C.H., M.C.K., D.A.L., N.M., and C.-Q.Z. are employees of GSK and own stocks/shares. D.E. has received compensation for being a trial investigator for Vitalink Research. M.K. has nothing to disclose. A.P. has received consultancy fees and board membership from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Mundipharma, and TEVA, and consultancy fees and payment for lectures from Sanofi. He has also received reimbursement of travel expenses from Avillion, reimbursement of travel expenses and payment for lectures from AstraZeneca, Boehringer Ingelheim, Chiesi, ELPEN Pharmaceutical, GSK, Menarini, MSD, Mundipharma, Novartis, TEVA, and Zambon, and research grants from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Pfizer, Sanofi, and TEVA.

Figures

Fig. 1. Study design.

FF fluticasone furoate, ITT intent-to-treat, TIO tiotropium, UMEC umeclidinium, VI vilanterol.

Fig. 2. Trough FEV1 (ITT population).

Least squares mean (95% CI) change from baseline in trough FEV1 at a Day 85 and b Days 28 and 84. CFB change from baseline, CI confidence interval, FEV1 forced expiratory volume in 1 s, FF fluticasone furoate, ITT intent-to-treat, LS least squares, TIO tiotropium, UMEC umeclidinium, VI vilanterol.

Fig. 3. SGRQ total score (ITT population).

a Least squares mean (95% CI) change from baseline in SGRQ total score and b proportion of SGRQ responders (≥4-point decrease in SGRQ total score) at Day 28 and Day 84. CFB change from baseline, CI confidence interval, FF fluticasone furoate, ITT intent-to-treat, LS least squares, SGRQ St George’s Respiratory Questionnaire, TIO tiotropium, UMEC umeclidinium, VI vilanterol.

Fig. 4. CAT Score (ITT population).

a Least squares mean (95% CI) change from baseline in CAT score and b proportion of CAT responders (≥2-point decrease in CAT score) at Day 28 and Day 84. CAT COPD Assessment Test, CFB change from baseline, CI confidence interval, FF fluticasone furoate, ITT intent-to-treat, LS least squares, TIO tiotropium, UMEC umeclidinium, VI vilanterol.

Fig. 5. Trough FEV1 for percent predicted FEV1 at screening subgroups (ITT population).

Least squares mean (95% CI) change from baseline in trough FEV1 at a Day 28, b Day 84, and c Day 85. CFB change from baseline, CI confidence interval, FEV1 forced expiratory volume in 1 s, FF fluticasone furoate, ITT intent-to-treat, LS least squares, TIO tiotropium, UMEC umeclidinium, VI vilanterol.