Efficacy and Safety of Budesonide/Glycopyrronium/Formoterol Fumarate versus Other Triple Combinations in COPD: A Systematic Literature Review and Network Meta-analysis

Abstract

In patients with chronic obstructive pulmonary disease (COPD) who experience further exacerbations or symptoms, despite being prescribed dual long-acting muscarinic antagonist (LAMA)/long-acting β 2 -agonist (LABA) or inhaled corticosteroid (ICS)/LABA therapies, triple ICS/LAMA/LABA therapy is recommended. A previous network meta-analysis showed comparable efficacy of the ICS/LAMA/LABA, budesonide/glycopyrronium bromide/formoterol fumarate (BUD/GLY/FOR) 320/18/9.6 µg, to other fixed-dose and open combination triple therapies at 24 weeks in COPD. Subsequently, the ETHOS study was published, including data for 8509 patients, assessing the efficacy and safety of BUD/GLY/FOR over 52 weeks. This network meta-analysis (NMA) was conducted to compare the relative efficacy, safety, and tolerability of BUD/GLY/FOR 320/18/9.6 µg with other fixed-dose and open combination triple therapies in COPD over 52 weeks, including data from ETHOS. A systematic literature review was conducted to identify ≥ 10-week randomized controlled trials, including ≥ 1 fixed-dose or open combination triple-therapy arm, in patients with moderate-to-very severe COPD. The methodologic quality and risk of bias of included studies were assessed. Study results were combined using a three-level hierarchical Bayesian NMA model to assess efficacy and safety outcomes at or over 24 and 52 weeks. Meta-regression and sensitivity analyses were used to assess heterogeneity across studies. Nineteen studies ( n = 37,741 patients) met the inclusion criteria of the review; 15 contributed to the base case network. LAMA/LABA dual combinations were combined as a single treatment group to create a connected network. Across all outcomes for exacerbations, lung function, symptoms, health-related quality of life, safety, and tolerability, the efficacy and safety of BUD/GLY/FOR were comparable to those of other triple ICS/LAMA/LABA fixed-dose (fluticasone furoate/umeclidinium/vilanterol and beclomethasone dipropionate/glycopyrronium bromide/formoterol fumarate) and open combinations at or over 24 and 52 weeks. Sensitivity analyses and meta-regression results for exacerbation outcomes were broadly in line with the base case NMA. In this NMA, BUD/GLY/FOR 320/18/9.6 μg showed comparable efficacy versus other ICS/LAMA/LABA fixed-dose or open combination therapies in terms of reducing exacerbation rates and improving lung function, symptoms and health-related quality of life in patients with moderate-to-very-severe COPD, in line with previously published meta-analysis results of triple combinations in COPD. The safety and tolerability profile of BUD/GLY/FOR was also found to be comparable to other triple combination therapies. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-021-01703-z.

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

“…A previous NMA comparing the efficacy of BUD/GLY/FOR triple therapy with other ICS/ LABA/LAMA triple combinations reported no significant differences between BUD/GLY/FOR and other fixed-dose (FF/UMEC/VI and BDP/ FOR/GLY) or open combination triple therapies (i.e., MITT) for COPD in terms of improvement in lung function and symptoms [33]. A later update to this NMA, including additional data from the ETHOS trial, reported similar findings [34]. It should be noted that in the first analysis, all ICS/LABA dual therapies were grouped under a single treatment class, and similarly in the updated analysis, all LAMA/LABA dual therapies were grouped together, meaning that no intraclass differences were captured.…”

Comparing the Efficacy and Safety Profile of Triple Fixed-Dose Combinations in COPD: A Meta-Analysis and IBiS Score

“…The search was performed in ClinicalTrials.gov, Cochrane Central Register of Controlled Trials (CENTRAL), Embase, EU Clinical Trials Register, MEDLINE, Scopus, and Web of Science, in order to provide relevant studies published up to 6 September 2021 (detailed information available in the Supplementary Materials ). Citations of previous published reviews were checked to select further pertinent RCTs, if any [ 21 ]. Literature search results were uploaded to Eppi-Reviewer 4 (EPPI-Centre Software, London, UK; detailed information available in the Supplementary Materials ).…”

Budesonide/Glycopyrronium/Formoterol: A Review in COPD

“…Results of systematic reviews and/or meta-analyses comparing the efficacy of inhaled triple ICS/LAMA/LABA therapy versus inhaled dual ICS/LABA or LAMA/LABA therapy for the treatment of COPD have indicated that inhaled triple ICS/LAMA/LABA therapy provides the greatest benefit in reducing the risk of exacerbations and improving lung function [ 38 – 40 ]. In addition, in network meta-analyses, the efficacy of budesonide/glycopyrronium/formoterol was comparable to that of other ICS/LAMA/LABA fixed-dose or open combination therapies in reducing exacerbation rates and improving lung function and COPD symptoms in patients with moderate to very severe COPD [ 41 , 42 ].…”