A Randomized, Double-Blind, Double-Dummy Study of Glycopyrrolate/Formoterol Fumarate Metered Dose Inhaler Relative to Umeclidinium/Vilanterol Dry Powder Inhaler in COPD

Maltais, François; Ferguson, Gary T.; Feldman, Gregory; Deslée, G.; Bourdin, Arnaud; Fjällbrant, Harald; Siwek-Posłuszna, Agnieszka; Jenkins, Martin; Martin, Ubaldo J.

doi:10.1007/s12325-019-01015-3

Cited by 26 publications

(41 citation statements)

References 26 publications

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“…A network meta-analysis found evidence of differences in efficacy between different LAMA/LABA combinations [55], suggesting that head-to-head clinical trial data are useful to illustrate differences between drugs within the LAMA/LABA class. Currently, four head-to-head studies have directly compared LAMA/LABA fixed-dose combination therapies [56][57][58]. An open label, 8-week, 2-period crossover study evaluated the efficacy and safety of once-daily umeclidinium/vilanterol compared with once-daily tiotropium/olodaterol in patients with moderate COPD [56].…”

Section: Within-class Lama/laba Comparisonsmentioning

confidence: 99%

“…A 24-week study (N = 1119) compared once-daily umeclidinium/ vilanterol with twice-daily formoterol/glycopyrrolate on measures of lung function in patients with moderate-to-very-severe COPD [58]. Formoterol/glycopyrrolate failed to demonstrate non-inferiority (threshold of −50 mL) to umeclidinium/vilanterol on the coprimary endpoint of trough FEV 1 (treatment difference: −87 mL; 97.5% CI: −117, −57), and demonstrated non-inferiority (but not superiority) to umeclidinium/vilanterol on peak FEV 1 within 2 hours post dosing (treatment difference: −3 mL; 97.5% CI: −33, 26).…”

Section: Within-class Lama/laba Comparisonsmentioning

confidence: 99%

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Current evidence for COPD management with dual long-acting muscarinic antagonist/long-acting β₂-agonist bronchodilators

Skolnik

Nguyen

Shrestha

et al. 2020

Postgraduate Medicine

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Long-acting inhaled bronchodilator medications are recommended as initial maintenance therapy for many patients with COPD. These medications include long-acting muscarinic antagonists (LAMA) and long-acting β 2-agonists (LABA). Combinations of long-acting bronchodilator agents (LAMA/LABA) and inhaled corticosteroids combined with LABA (ICS/LABA) are also used as initial or follow-up therapy in patients with more severe symptoms or at risk of COPD exacerbations. This review summarizes the position of LAMA/LABA combinations in treatment recommendations, and the evidence supporting their placement relative to LAMA monotherapy and ICS/LABA combination therapy, as well as differences within the LAMA/LABA class. Most studies show that LAMA/LABA treatment leads to greater improvements in lung function and symptoms than LAMA monotherapy or ICS/LABA treatment. There are fewer studies comparing the impact of different medication classes on patients' risk of exacerbations; however, the available evidence suggests that LAMA/LABA treatment and LAMA monotherapy lead to a similar reduction in exacerbation risk, while the effect of LAMA/LABA compared with ICS/LABA remains unclear. The incidence of adverse events is similar with LAMA/LABA and LAMA alone. There is a lower risk of pneumonia with LAMA/LABA compared with ICS/LABA. This evidence supports the use of LAMA/LABA combinations as an initial maintenance therapy option for symptomatic patients with low exacerbation risk and severe breathlessness or patients with severe symptoms who are at risk of exacerbations, and as follow-up treatment in patients with uncontrolled symptoms or exacerbations on bronchodilator monotherapy.

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Section: Within-class Lama/laba Comparisonsmentioning

confidence: 99%

Section: Within-class Lama/laba Comparisonsmentioning

confidence: 99%

Current evidence for COPD management with dual long-acting muscarinic antagonist/long-acting β₂-agonist bronchodilators

Skolnik

Nguyen

Shrestha

et al. 2020

Postgraduate Medicine

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“…However, the lung function response with glycopyrrolate/formoterol fumarate in the AERISTO study was lower than that observed in previous studies of this combination. 18 In Study A2349 and Study A2350, indacaterol/glycopyrrolate was not non-inferior to umeclidinium/vilanterol in change from baseline in FEV 1 AUC 0-24h at Week 12, which may have been due to the narrow non-inferiority margin of -20 mL. 19 In Study GSK204990, umeclidinium/vilanterol was superior to tiotropium/olodaterol in change from baseline in trough FEV 1 at Week 8.…”

Section: Discussionmentioning

confidence: 92%

“…4 Where assessed, the results of this review demonstrate that LAMA/LABA FDCs have comparable efficacy in improving symptoms, quality of life, and exacerbations when assessed in head-to-head studies. However, it should be noted that quality of life and symptoms were only assessed in two of the four head-to-head studies, 18,20 and exacerbations were only assessed as an exploratory efficacy outcome in the AERISTO study. 18 Moreover, none of the head-to-head studies assessed health status using SGRQ, a disease-specific health-related quality of life questionnaire.…”

Section: Discussionmentioning

confidence: 99%

“…Using the results of the systematic literature review, four RCTs from three publications were identified that provided head-to-head comparison of LAMA/LABA FDCs in patients with moderate-to-very severe airflow limitation in COPD (Figure 1): the AERISTO study, a 24-week, multicenter, international, Phase IIIb, double-blind study; 18 Study A2349 and Study A2350, two identically designed 12-week, multicenter, US, Phase III, doubleblind studies; 19 and Study GSK204990, an 8-week, multicenter, international, Phase IV, open-label study. 20 In terms of the characteristics of the studies identified in the literature search, some differences were noted across the studies in treatment duration, study design (parallelgroup vs the crossover), the number of patients randomized, and levels of blinding ( Table 1).…”

Section: Direct Evidence: Study Characteristicsmentioning

confidence: 99%

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<p>Efficacy and Safety of LAMA/LABA Fixed-Dose Combination Therapies in Chronic Obstructive Pulmonary Disease: A Systematic Review of Direct and Indirect Treatment Comparisons</p>

Hurst

Gruffydd-Jones

Biswas

et al. 2020

COPD

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Background: This literature review assessed comparative efficacy and safety of long-acting muscarinic antagonist/long-acting β 2-agonist (LAMA/LABA) fixed-dose combinations (FDCs) in patients with COPD and moderate-to-very severe airflow limitation, using evidence from direct (head-to-head) and indirect treatment comparisons. Methods: Two systematic literature reviews were conducted to identify direct comparisons (head-to-head randomized controlled trials [RCTs]) and indirect comparisons (network metaanalyses [NMAs]; indirect treatment comparisons; meta-analyses) in patients with COPD with moderate-to-very severe airflow limitation. Study/Analysis characteristics, eligibility criteria, patient characteristics, and overall conclusions were extracted from relevant publications. The review of indirect comparisons focused on NMAs reporting efficacy outcomes at 12 and 24 weeks of treatment (established durations of symptomatic studies in COPD recommended by regulators). Results: Direct comparisons: Four RCTs that provided head-to-head comparisons of LAMA/ LABA FDCs were identified, and these varied in their study design, included patient population and reported endpoints. While some differences in lung function outcomes were noted, where assessed, LAMA/LABA FDCs had comparable efficacy in improving symptoms, health status, exacerbations, and comparable safety profiles. However, the differences in study methodology and patient characteristics between these studies made it difficult to draw generalizable conclusions regarding the comparative effectiveness of LAMA/LABA FDCs from the direct comparisons alone. Indirect comparisons: Six NMAs were identified that reported indirect comparisons between LAMA/ LABA FDCs; five of these were within the pre-defined scope of this review. Although the scope of each NMA varied, all five concluded that LAMA/LABA FDCs were generally comparable in terms of lung function improvements, patient-reported outcomes, and safety (where assessed). Conclusion: Although there were some inconsistencies between the outcomes of RCTs and NMAs for lung function, the totality of lung function, symptoms, exacerbations, and safety data suggests that currently available LAMA/LABA FDCs have comparable efficacy and safety in patients with COPD and moderate-to-very severe airflow limitation.

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Regional Gas Exchange Measured by ¹²⁹Xe Magnetic Resonance Imaging Before and After Combination Bronchodilators Treatment in Chronic Obstructive Pulmonary Disease

Mummy

Coleman

Wang

et al. 2021

Magnetic Resonance Imaging

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Background Hyperpolarized 129Xe magnetic resonance imaging (MRI) provides a non‐invasive assessment of regional pulmonary gas exchange function. This technique has demonstrated that chronic obstructive pulmonary disease (COPD) patients exhibit ventilation defects, reduced interstitial barrier tissue uptake, and poor transfer to capillary red blood cells (RBCs). However, the behavior of these measurements following therapeutic intervention is unknown. Purpose To characterize changes in 129Xe gas transfer function following administration of an inhaled long‐acting beta‐agonist/long‐acting muscarinic receptor antagonist (LABA/LAMA) bronchodilator. Study Type Prospective. Population Seventeen COPD subjects (GOLD II/III classification per Global Initiative for Chronic Obstructive Lung Disease criteria) were imaged before and after 2 weeks of LABA/LAMA therapy. Field Strength/Sequences Dedicated ventilation imaging used a multi‐slice 2D gradient echo sequence. Three‐dimensional images of ventilation, barrier uptake, and RBC transfer used an interleaved, radial, 1‐point Dixon sequence. Imaging was acquired at 3 T. Assessment 129Xe measurements were quantified before and after LABA/LAMA treatment by ventilation defect + low percent (vendef + low) and by barrier uptake and RBC transfer relative to a healthy reference population (bar%ref and RBC%ref). Pulmonary function tests, including diffusing capacity of the lung for carbon monoxide (DLCO), were also performed before and after treatment. Statistical Tests Paired t‐test, Pearson correlation coefficient (r). Results Baseline vendef + low was 57.8 ± 8.4%, bar%ref was 73.2 ± 19.6%, and RBC%ref was 36.5 ± 13.6%. Following treatment, vendef + low decreased to 52.5 ± 10.6% (P < 0.05), and improved in 14/17 (82.4%) of subjects. However, RBC%ref decreased in 10/17 (58.8%) of subjects. Baseline measurements of bar%ref and DLCO were correlated with the degree of post‐treatment change in vendef + low (r = −0.49, P < 0.05 and r = −0.52, P < 0.05, respectively). Conclusion LABA/LAMA therapy tended to preferentially improve ventilation in subjects whose 129Xe barrier uptake and DLCO were relatively preserved. However, newly ventilated regions often revealed RBC transfer defects, an aspect of lung function opaque to spirometry. These microvasculature abnormalities must be accounted for when assessing the effects of LABA/LAMA therapy. Level of Evidence 1 Technical Efficacy Stage 4

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A Randomized, Double-Blind, Double-Dummy Study of Glycopyrrolate/Formoterol Fumarate Metered Dose Inhaler Relative to Umeclidinium/Vilanterol Dry Powder Inhaler in COPD

Cited by 26 publications

References 26 publications

Current evidence for COPD management with dual long-acting muscarinic antagonist/long-acting β₂-agonist bronchodilators

Current evidence for COPD management with dual long-acting muscarinic antagonist/long-acting β₂-agonist bronchodilators

<p>Efficacy and Safety of LAMA/LABA Fixed-Dose Combination Therapies in Chronic Obstructive Pulmonary Disease: A Systematic Review of Direct and Indirect Treatment Comparisons</p>

Regional Gas Exchange Measured by ¹²⁹Xe Magnetic Resonance Imaging Before and After Combination Bronchodilators Treatment in Chronic Obstructive Pulmonary Disease

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A Randomized, Double-Blind, Double-Dummy Study of Glycopyrrolate/Formoterol Fumarate Metered Dose Inhaler Relative to Umeclidinium/Vilanterol Dry Powder Inhaler in COPD

Cited by 26 publications

References 26 publications

Current evidence for COPD management with dual long-acting muscarinic antagonist/long-acting β2-agonist bronchodilators

Current evidence for COPD management with dual long-acting muscarinic antagonist/long-acting β2-agonist bronchodilators

<p>Efficacy and Safety of LAMA/LABA Fixed-Dose Combination Therapies in Chronic Obstructive Pulmonary Disease: A Systematic Review of Direct and Indirect Treatment Comparisons</p>

Regional Gas Exchange Measured by 129Xe Magnetic Resonance Imaging Before and After Combination Bronchodilators Treatment in Chronic Obstructive Pulmonary Disease

Contact Info

Product

Resources

About

Current evidence for COPD management with dual long-acting muscarinic antagonist/long-acting β₂-agonist bronchodilators

Current evidence for COPD management with dual long-acting muscarinic antagonist/long-acting β₂-agonist bronchodilators

Regional Gas Exchange Measured by ¹²⁹Xe Magnetic Resonance Imaging Before and After Combination Bronchodilators Treatment in Chronic Obstructive Pulmonary Disease