Efficacy of Budesonide/Glycopyrronium/Formoterol Fumarate Metered Dose Inhaler (BGF MDI) Versus Other Inhaled Corticosteroid/Long-Acting Muscarinic Antagonist/Long-Acting β2-Agonist (ICS/LAMA/LABA) Triple Combinations in COPD: A Systematic Literature Review and Network Meta-analysis

Ferguson, Gary T.; Darken, Patrick; Ballal, Shaila; Siddiqui, Mohammad Khubeb; Singh, Balwant; Attri, Sumeet; Holmgren, Ulf; Nigris, Enrico De

doi:10.1007/s12325-020-01311-3

Cited by 18 publications

(20 citation statements)

References 36 publications

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“…The present study shows that compared with single-inhaler dual therapy, single-inhaler triple therapy significantly reduced the frequency of moderate and severe exacerbation episodes. Our results are consistent with the findings of the most recent meta-analyses [ 9 , 24 ]. In the ETHOS [ 17 ] study, which compared GLY/FOR to BUD/GLY/FOR (320 μg of budesonide), the frequency of moderate and severe exacerbation episodes decreased by 24% with BUD/GLY/FOR vs. GLY/FOR.…”

Section: Discussionsupporting

confidence: 93%

“…In some RCTs comparing triple therapy with dual therapy in COPD, there might be a bias resulting from the use of multiple inhaler devices. Single-inhaler therapy has been shown to improve lung function and health status [ 8 , 9 ], but evidence of a reduction in mortality with single-inhaler triple therapy versus single-inhaler dual therapy has not been well documented in previous meta-analyses.…”

Section: Introductionmentioning

confidence: 99%

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Single-inhaler triple vs single-inhaler dual therapy in patients with chronic obstructive pulmonary disease: a meta-analysis of randomized control trials

Long

Janssens³

et al. 2021

Respir Res

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Background In some RCTs comparing triple therapy with dual therapy in COPD, there might be a bias resulting from the use of multiple inhaler devices. This meta-analysis included only RCTs that compared ICS/LABA/LAMA vs. LABA/LAMA or ICS/LABA using a single device. Methods We systematically reviewed randomized controlled trials (RCTs) of single-inhaler triple therapy in patients with COPD. We searched the PubMed, MEDLINE (OvidSP), EMBASE and Cochrane Library databases to investigate the effect of single-inhaler triple therapy in COPD. The primary end points were the effect of single-inhaler triple therapy compared with single-inhaler dual therapy on all-cause mortality, the risk of acute exacerbation of COPD (AECOPD), and some safety endpoints. The Cochrane Collaboration tool was used to assess the quality of each randomized trial and the risk of bias. Results A total of 25,171 patients suffering from COPD were recruited for the 6 studies. This meta-analysis indicated that single-inhaler triple therapy resulted in a significantly lower rate of all-cause mortality than LABA/LAMA FDC (risk ratio, 0.70; 95% CI 0.56‐0.88). Single-inhaler triple therapy reduced the risk of exacerbation and prolonged the time to first exacerbation compared with single-inhaler dual therapy. The FEV1 increased significantly more under single-inhaler triple therapy than under ICS/LABA FDC (mean difference, 103.4 ml; 95% CI 64.65‐142.15). The risk of pneumonia was, however, significantly higher with ICS/LAMA/LABA FDC than with LABA/LAMA FDC (risk ratio, 1.55; 95% CI 1.35–1.80). Conclusions This meta-analysis suggests that single-inhaler triple therapy is effective in reducing the risk of death of any cause and of moderate or severe exacerbation in COPD patients. However, the risk of pneumonia is higher with ICS/LAMA/LABA FDC than with LABA/LAMA FDC. Trial registration PROSPERO #CRD42020186726.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Single-inhaler triple vs single-inhaler dual therapy in patients with chronic obstructive pulmonary disease: a meta-analysis of randomized control trials

Long

Janssens³

et al. 2021

Respir Res

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“…The relevant study results were combined using a three-level hierarchical Bayesian NMA, as previously described in Ferguson et al [ 20 ]. For convenience, the methods are summarized here.…”

Section: Methodsmentioning

confidence: 99%

“…In the Phase III ETHOS (NCT02465567) and KRONOS (NCT02497001) studies, BUD/GLY/FOR showed benefits in reducing COPD exacerbations and improving lung function and symptoms versus dual LAMA/LABA and ICS/LABA therapies [ 18 , 19 ]. A recent NMA showed that BUD/GLY/FOR had similar efficacy to other ICS/LAMA/LABA fixed-dose and open combination therapies in reducing exacerbation rates, and improving lung function and symptoms at 24 weeks, in patients with moderate-to-very-severe COPD [ 20 ]. Subsequently, the recent ETHOS study has provided a large body of evidence regarding the efficacy and safety of BUD/GLY/FOR over 52 weeks [ 19 ], allowing for comparisons with other triple therapies that have been assessed in 1-year studies.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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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.

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“…Published systematic reviews [ 12 , 13 ] and pairwise meta-analyses [ 14 – 17 ] on previous RCTs [ 18 – 25 ] claimed that triple therapy in FDCs, e.g., BDP/FF/G, FF/UMEC/VI and BUD/GLY/FF, could be better than monotherapy and dual therapy in improving lung function and quality of life. The only network meta-analysis [ 26 ] included merely seven [ 18 – 23 , 27 ] RCTs with 8762 participants on triple therapy in FDCs well before August 2019. It left out the 4987 participants and new findings from recent large-scale RCTs [ 24 , 25 ] on triple therapy.…”

Section: Introductionmentioning

confidence: 99%

Comparative efficacy of single-inhaler triple therapies for COPD: A protocol for systematic review and network meta-analysis

Jiang

Leung

2021

PLoS ONE

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Introduction 2021 Global Initiative for Chronic Obstructive Lung Disease (GOLD) Reports recommends that patients with clinically significant symptoms and exacerbations of chronic obstructive pulmonary disease (COPD) should escalate to triple therapy, a combined use of inhaled corticosteroids (ICS), long-acting muscarinic antagonists (LAMA) and long-acting b2-agonists (LABA)(ICS/LAMA/LABA). Triple therapy in fixed-dose combinations (FDCs), i.e., combining ICS, LABA with LAMA and administrating by a single inhalation device, has appeared in recent years. This study aims to compare the efficacy of triple therapy in FDCs in treating patients with moderate to severe COPD. Methods and analyses Literature search will be conducted on PubMed, Embase and Web of science, according to pre-specified and corresponding search strategies, for relevant reports published since the inception dates of the databases. Randomised controlled trials (RCT) which compared the triple therapy in FDCs with other pharmacological therapies will be included. The Cochrane risk of bias assessment tool (RoB 2) will be used to assess the RCT quality. The outcomes will be analyzed as rate ratios and mean differences under a random-effects model in a frequentist network meta-analysis (NMA). Additional statistical analyses including subgroup analysis, sensitivity analysis, and publication bias analysis will be performed to assess the evidential heterogeneity and robustness. The strength of evidence from the NMA will be evaluated with the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) methods. Ethics and dissemination No ethics approval is required as this systematic review and network meta-analysis do not collect confidential personal data and do not carry out interventions in treating patients. Protocol registration number CRD42021240823.

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Efficacy of Budesonide/Glycopyrronium/Formoterol Fumarate Metered Dose Inhaler (BGF MDI) Versus Other Inhaled Corticosteroid/Long-Acting Muscarinic Antagonist/Long-Acting β2-Agonist (ICS/LAMA/LABA) Triple Combinations in COPD: A Systematic Literature Review and Network Meta-analysis

Cited by 18 publications

References 36 publications

Single-inhaler triple vs single-inhaler dual therapy in patients with chronic obstructive pulmonary disease: a meta-analysis of randomized control trials

Single-inhaler triple vs single-inhaler dual therapy in patients with chronic obstructive pulmonary disease: a meta-analysis of randomized control trials

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

Comparative efficacy of single-inhaler triple therapies for COPD: A protocol for systematic review and network meta-analysis

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