Fluticasone Furoate/Umeclidinium/Vilanterol (FF/UMEC/VI) Triple Therapy Compared with Other Therapies for the Treatment of COPD: A Network Meta-Analysis

Abstract

Introduction: Randomized controlled trials (RCTs) comparing triple therapies (inhaled corticosteroid [ICS], long-acting β₂-agonist [LABA], and long-acting muscarinic antagonist [LAMA]) for the treatment of chronic obstructive pulmonary disease (COPD) are limited. This network meta-analysis (NMA) investigated the comparative efficacy of single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus any triple (ICS/LABA/LAMA) combinations and dual therapies in patients with COPD.

Methods: This NMA was conducted on the basis of a systematic literature review (SLR), which identified RCTs in adults aged at least 40 years with COPD. The RCTs compared different ICS/LABA/LAMA combinations or an ICS/LABA/LAMA combination with any dual therapy (ICS/LABA or LAMA/LABA). Outcomes of interest included forced expiratory volume in 1 s (FEV₁), annualized rate of combined moderate and severe exacerbations, St George's Respiratory Questionnaire (SGRQ) total score and SGRQ responders, transition dyspnea index focal score, and rescue medication use (RMU). Analyses were conducted at 24 weeks (primary endpoint), and 12 and 52 weeks (if feasible).

Results: The NMA was informed by five trials reporting FEV₁ at 24 weeks. FF/UMEC/VI was statistically significantly more effective at increasing trough FEV₁ (based on change from baseline) than all triple comparators in the network apart from UMEC + FF/VI. The NMA was informed by 17 trials reporting moderate or severe exacerbation endpoints. FF/UMEC/VI demonstrated statistically significant improvements in annualized rate of combined moderate or severe exacerbations versus single-inhaler budesonide/glycopyrronium bromide/formoterol fumarate (BUD/GLY/FOR). At 24 weeks, the NMA was informed by five trials. FF/UMEC/VI showed statistically significant improvements in annualized rate of combined moderate or severe exacerbations versus UMEC + FF/VI and BUD/GLY/FOR. FF/UMEC/VI also demonstrated improvements in mean SGRQ score versus other triple therapy comparators at 24 weeks, and a significant reduction in RMU compared with BUD/GLY/FOR (160/18/9.6).

Conclusion: The findings of this NMA suggest favorable efficacy with single-inhaler triple therapy comprising FF/UMEC/VI. Further analysis is required as additional evidence becomes available.

Keywords: Beclomethasone dipropionate/formoterol fumarate dihydrate/glycopyrronium bromide; Budesonide/glycopyrronium bromide/formoterol fumarate; COPD; Fluticasone furoate/umeclidinium/vilanterol; Indirect treatment comparison; Network meta-analysis; Triple therapy.

Fig. 1

PRISMA flowchart. CSR clinical study report, GSK GlaxoSmithKline, LABA long-acting β₂-agonist, LAMA long-acting muscarinic antagonist, NMA network meta-analysis, SLR systematic literature review

Fig. 2

Mean change from baseline in trough FEV₁ of FF/UMEC/VI versus a triple therapy comparators at 24 weeks, b dual therapy comparators at 24 weeks, c triple therapy comparators at 12 weeks, and d dual therapy comparators/TIO at 12 weeks. BDP beclomethasone dipropionate, BUD budesonide, CFB change from baseline, CI confidence interval, FEV₁ forced expiratory volume in 1 s, FOR formoterol, FP fluticasone propionate, FF fluticasone furoate, GLY glycopyrronium bromide, IND indacaterol, SAL salmeterol, TIO tiotropium, UMEC umeclidinium, VI vilanterol

Fig. 3

Annualized moderate or severe exacerbation rates—FF/UMEC/VI versus a triple therapy comparators and b dual therapy comparators (trials with at least 24 weeks follow-up) comparators (all trials). BUD budesonide, CI confidence interval, FF fluticasone furoate, FOR formoterol fumarate, GLY glycopyrronium bromide, IR incidence rate, UMEC umeclidinium, VI vilanterol

Fig. 4

Annualized moderate or severe exacerbation rates—FF/UMEC/VI versus a triple therapy comparators and b dual therapy comparators/TIO (all trials). BUD budesonide, BDP beclomethasone dipropionate, CI confidence interval, FF fluticasone furoate, FOR formoterol fumarate, FP fluticasone propionate, GLY glycopyrronium bromide, IND indacaterol, IR incidence rate, SAL salmeterol, TIO tiotropium, UMEC umeclidinium, VI vilanterol

Fig. 5

Mean change from baseline in total SGRQ score of FF/UMEC/VI versus a triple therapy comparators at 24 weeks, b dual therapy comparators at 24 weeks, c triple therapy comparators at 12 weeks, and d dual therapy comparators/TIO at 12 weeks. BUD budesonide, CFB change from baseline, CI confidence interval, FF fluticasone furoate, FOR formoterol fumarate, GLY glycopyrronium bromide, IND indacaterol, SGRQ St George’s Respiratory Questionnaire, TIO tiotropium, UMEC umeclidinium, VI vilanterol

Fig. 6

SGRQ responder analysis—FF/UMEC/VI versus a triple therapy comparators and b dual therapy comparators/TIO at 12 weeks. BUD budesonide, BDP beclomethasone dipropionate, CI confidence interval, FE fixed effect, FF fluticasone furoate, FOR formoterol fumarate, NMA network meta-analysis, SGRQ St George’s Respiratory Questionnaire, TIO tiotropium, UMEC umeclidinium, VI vilanterol

Fig. 7

Transition dyspnea index focal score—FF/UMEC/VI versus a triple therapy comparators and b dual therapy comparators at 24 weeks. BUD budesonide, CFB change from baseline, CI confidence interval, FF fluticasone furoate, FOR formoterol fumarate, GLY glycopyrronium bromide, UMEC umeclidinium, VI vilanterol

Fig. 8

Rescue medication use—FF/UMEC/VI versus a triple therapy comparators and b dual therapy comparators at 24 weeks. BUD budesonide, CFB change from baseline, CI confidence interval, FF fluticasone furoate, FOR formoterol fumarate, GLY glycopyrronium bromide, UMEC umeclidinium, VI vilanterol

Fig. 9

Rescue medication use—FF/UMEC/VI versus a triple therapy comparators and b dual therapy comparators at 12 weeks. BUD budesonide, CFB change from baseline, CI confidence interval, FF fluticasone furoate, FOR formoterol fumarate, UMEC umeclidinium, VI vilanterol