Introduction

Chronic obstructive pulmonary disease (COPD) patients remain symptomatic and are at a risk of exacerbations despite receiving dual therapy with either inhaled corticosteroid/ long-acting β2-agonist (ICS/LABA) or LABA/long-acting muscarinic antagonist (LABA/LAMA). Triple therapy comprising ICS/LABA/LAMA has been recommended for such patients and has shown benefits over dual therapy with respect to lung function and exacerbations. Once-daily single inhaler triple therapy (SITT) with fluticasone furoate, umeclidinium and vilanterol (FF/UMEC/VI) has been approved by USFDA and European Medicines Agency. However, there are no randomized controlled trials (RCTs) or head to-head trials which compare the efficacy of different SITT regimens.

Aim

To compare the efficacy of single-inhaler FF/UMEC/VI with other ICS/LABA/LAMA combinations and dual therapies in patients with COPD.

Method

Study Design

• Network meta-analysis, an extension of a traditional pairwise meta-analysis (where all included trials compare the same intervention with the same comparator) by including multiple different pairwise comparisons across a range of different interventions

Data - Sources, Extraction and Synthesis

• A systematic literature review (SLR), was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA)
• RCTs that included adults >40 years of age with a diagnosis of COPD were identified
• The selected RCTs compared different ICS/LABA/LAMA combinations with each other or an ICS/LABA/LAMA combination with any dual therapy (ICS/LABA or LAMA/LABA)
• An extensive search of electronic databases including MEDLINE, MEDLINE In Process, EMBASE, and COCHRANE was performed
• The analyses were conducted using the frequentist weighted regression-based approach at 24 weeks, and at 12 and 52 weeks, if feasible

Endpoints

Primary Endpoint

• Trough forced expiratory volume in 1 s (FEV₁) - Mean change from baseline at 24 weeks

Secondary Endpoints

• Annualized rate of combined moderate and severe exacerbations
• St George's Respiratory Questionnaire (SGRQ) total score at duration of week 12, 24 and 52
• Transition dyspnea index (TDI) score at week 12 and 24. Also at 52 weeks
• Rescue medication use (RMU) at 12, 24 and 52 weeks

Results

• The network meta-analysis included 23 trials
• Five trials reporting FEV₁ at 24 weeks demonstrated significant increase in trough FEV₁ from baseline with FF/UMEC/VI as compared to all triple therapy regimens in the network apart from UMEC + FF/VI
• Clinically significant improvement in FEV₁ was seen with FF/UMEC/VI as compared to single-inhaler budesonide/glycopyrronium bromide/formoterol fumarate (BUD/GLY/FOR)
• FF/UMEC/VI was superior to all triple comparators apart from tiotropium (TIO)+salmeterol/fluticasone propionate, TIO+BDP/FOR, and UMEC+FF/VI with respect to increase in trough FEV₁ from baseline at 12 weeks
• Moderate or severe exacerbation endpoints were informed by 17 trials, which reported that FF/UMEC/VI resulted in significant improvements in annualized rate of combined moderate or severe exacerbations vs UMEC (62.5) + FF/VI (100/25) as well as BUD/GLY/FOR (320/18/9.6) and (160/18/9.6)
• At 24 weeks, as compared to the other triple therapy regimens, FF/UMEC/VI showed remarkably greater improvements in the mean SGRQ score
• As per the results of 5 trials which reported data on TDI, significant improvement in TDI scores at 24 weeks was demonstrated with FF/UMEC/VI vs UMEC+FF/VI and BUD/GLY/FOR (320/18/9.6)
• The use of rescue medication was significantly reduced with FF/UMEC/VI vs BUD/GLY/FOR (160/18/9.6)

Conclusion

• The efficacy of single-inhaler triple therapy comprising fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) was favorable compared to other single-inhaler or multiple-inhaler triple therapy regimens
• Significant improvements in FEV₁, annual rate of moderate exacerbations and severe exacerbations were reported with FF/UMEC/VI

Adv Ther. 2022 Sep;39(9):3957-3978. Doi: 10.1007/s12325-022-02231-0.