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Expert Review of Respiratory Medicine Sep 2021: Aclidinium/formoterol is a long-acting muscarinic antagonist (LAMA) and long-acting β-agonist (LABA) dual bronchodilator used as a maintenance treatment for patients... (Review)
Review
: Aclidinium/formoterol is a long-acting muscarinic antagonist (LAMA) and long-acting β-agonist (LABA) dual bronchodilator used as a maintenance treatment for patients with chronic obstructive pulmonary disease (COPD). The efficacy of aclidinium/formoterol has been demonstrated consistently in patients with moderate-to-severe COPD versus placebo and monocomponents, with a comparable safety profile.: This review examines recent research findings that expand our understanding of the impact of aclidinium/formoterol on the burden of COPD. Reviewed outcomes include improvements in lung function, respiratory symptoms, health-related quality of life, exercise tolerance, exacerbation rates, and clinically important deteriorations. In addition, the reported cardiovascular safety of aclidinium and current LAMA/LABA treatment recommendations are discussed.: Aclidinium/formoterol reduces disease burden in patients with COPD, including those that are treatment-naïve, without a significant increase in safety risk compared with monotherapies. Furthermore, evidence supports an improvement in lung function over a 24-hour period with aclidinium/formoterol treatment versus monotherapy and placebo, which may offer an advantage over some once-daily LAMA/LABA combinations. In summary, the recent evidence discussed in this review adds weight to the use of LAMA/LABA combinations as an initial therapy for certain patients newly diagnosed with COPD.
Topics: Adrenergic beta-2 Receptor Agonists; Bronchodilator Agents; Drug Combinations; Formoterol Fumarate; Humans; Pulmonary Disease, Chronic Obstructive; Quality of Life; Tropanes
PubMed: 34137664
DOI: 10.1080/17476348.2021.1920403 -
Expert Review of Respiratory Medicine Jan 2021Long acting bronchodilators are nowadays the central treatment for management of stable COPD. Several combinations exist within the market with different formulation... (Review)
Review
INTRODUCTION
Long acting bronchodilators are nowadays the central treatment for management of stable COPD. Several combinations exist within the market with different formulation devices. This article reviews a recent dual combination of glycopyrronium and formoterol fumarate in an innovative pMDI-fixed dual combination, Bevespi® Aerosphere.
AREAS COVERED
This article explored the literature to understand the place of this novel combination and unique delivery drug device in today's therapeutic arsenal. Clinical efficacy and safety have been evaluated through the different clinical trials published in public databases.
EXPERT OPINION
Within the fixed-dose combinations, Glycopyrrolate and formoterol fumarate offer a credible unique pMDI option to be given twice a day. LABA-LAMA offers an ICS-free alternative in COPD pharmacology which represents an important treatment option given the current debate over whether or not, maintenance triple therapy combined with ICS are benefic in the long term.
Topics: Administration, Inhalation; Bronchodilator Agents; Formoterol Fumarate; Glycopyrrolate; Humans; Pulmonary Disease, Chronic Obstructive
PubMed: 32772582
DOI: 10.1080/17476348.2020.1807946 -
Drugs Aug 2021Budesonide/glycopyrronium/formoterol (BREZTRI AEROSPHERE™; TRIXEO AEROSPHERE™) is an inhaled fixed-dose combination of the inhaled corticosteroid (ICS) budesonide,... (Review)
Review
Budesonide/glycopyrronium/formoterol (BREZTRI AEROSPHERE™; TRIXEO AEROSPHERE™) is an inhaled fixed-dose combination of the inhaled corticosteroid (ICS) budesonide, the long-acting muscarinic antagonist (LAMA) glycopyrronium bromide and the long-acting β-agonist (LABA) formoterol fumarate approved for the maintenance treatment of chronic obstructive pulmonary disease (COPD). It is delivered via a pressurized metered-dose Aerosphere inhaler and is formulated using co-suspension delivery technology. In two pivotal phase III trials of 24-52 weeks' duration, budesonide/glycopyrronium/formoterol reduced the rates of moderate/severe COPD exacerbations and improved lung function to a greater extent than budesonide/formoterol and/or glycopyrronium/formoterol. Budesonide/glycopyrronium/formoterol also demonstrated beneficial effects on dyspnoea, rescue medication requirements and health-related quality of life (HR-QOL), and reduced the risk of all-cause mortality. Budesonide/glycopyrronium/formoterol was generally well tolerated, with the tolerability profile being generally similar to that of the individual components. Budesonide/glycopyrronium/formoterol provides a useful and convenient option for the maintenance treatment of COPD, including for patients whose disease is inadequately controlled with dual ICS/LABA or LAMA/LABA therapy.
Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Bronchodilator Agents; Budesonide; Drug Combinations; Formoterol Fumarate; Glucocorticoids; Glycopyrrolate; Humans; Metered Dose Inhalers; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive
PubMed: 34342835
DOI: 10.1007/s40265-021-01562-6 -
Advances in Therapy Jun 2021In patients with chronic obstructive pulmonary disease (COPD) who experience further exacerbations or symptoms, despite being prescribed dual long-acting muscarinic... (Meta-Analysis)
Meta-Analysis
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-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.
Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Bayes Theorem; Bronchodilator Agents; Budesonide; Drug Combinations; Formoterol Fumarate; Fumarates; Glycopyrrolate; Humans; Muscarinic Antagonists; Network Meta-Analysis; Pulmonary Disease, Chronic Obstructive; Quality of Life
PubMed: 33929661
DOI: 10.1007/s12325-021-01703-z -
Expert Opinion on Pharmacotherapy 2016One of the most widely used fixed combinations in asthma management is dry powder budesonide+formoterol fumarate dihydrate which is commercially available as Symbicort... (Review)
Review
INTRODUCTION
One of the most widely used fixed combinations in asthma management is dry powder budesonide+formoterol fumarate dihydrate which is commercially available as Symbicort Turbuhaler(®) (and generic products), Easyhaler Bufomix(®) and DuoRespSpiromax(®) inhaler. The aim of this paper was to review the fixed dry powder combination of inhaled budesonide+formoterol fumarate dihydrate for asthma treatment in adolescents and adults.
AREAS COVERED
A literature search using relevant search terms, reference lists for reviews and meta-analyses was performed.
EXPERT OPINION
In symptomatic adolescent and adult patients with asthma maintenance and reliever therapy with a single-inhaler fixed combination of dry powder budesonide+formoterol fumarate dihydrate is an evidenced option. The combination treatment is convenient to patients. It reduces the number of exacerbations requiring treatment with oral corticosteroids. In some patients the strategy may also reduce the total intake of inhaled corticosteroids over time. Whether important outcome measures of asthma treatment, such as hospital admission and emergency room visit rates, may be reduced is less well documented since the published studies may have been influenced by publication bias. Non-pharmaceutical company-sponsored research evaluating such measures is needed. There is no evidence for the use of single inhaler fixed combinations of inhaled corticosteroids+long-acting β(2)-agonists in children (<12 years of age), and budesonide+formoterol fumarate dihydrate should not be prescribed to the age group.
Topics: Administration, Inhalation; Anti-Asthmatic Agents; Asthma; Budesonide; Drug Combinations; Formoterol Fumarate; Hospitalization; Humans; Nebulizers and Vaporizers
PubMed: 27070946
DOI: 10.1517/14656566.2016.1165207 -
Respiratory Medicine 2019Single inhaler triple therapies providing an inhaled corticosteroid, a long-acting muscarinic antagonist, and a long-acting β-agonist (ICS/LAMA/LABAs) are an emerging... (Randomized Controlled Trial)
Randomized Controlled Trial
A phase III study of triple therapy with budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler 320/18/9.6 μg and 160/18/9.6 μg using co-suspension delivery technology in moderate-to-very severe COPD: The ETHOS study protocol.
BACKGROUND
Single inhaler triple therapies providing an inhaled corticosteroid, a long-acting muscarinic antagonist, and a long-acting β-agonist (ICS/LAMA/LABAs) are an emerging treatment option for chronic obstructive pulmonary disease (COPD). Nevertheless, questions remain regarding the optimal patient population for triple therapy as well as the benefit:risk ratio of ICS treatment.
METHODS
ETHOS is an ongoing, randomized, double-blind, multicenter, parallel-group, 52-week study in symptomatic patients with moderate-to-very severe COPD and a history of exacerbation(s) in the previous year. Two doses of single inhaler triple therapy with budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler (BGF MDI 320/18/9.6 μg and 160/18/9.6 μg) will be compared to glycopyrrolate/formoterol fumarate (GFF) MDI 18/9.6 μg and budesonide/formoterol fumarate (BFF) MDI 320/9.6 μg, all formulated using co-suspension delivery technology. Outcomes include the rate of moderate/severe (primary endpoint) and severe COPD exacerbations, symptoms, quality of life, and all-cause mortality. Sub-studies will assess lung function and cardiovascular safety.
STUDY POPULATION
From June 2015-July 2018, 16,044 patients were screened and 8572 were randomized. Preliminary baseline demographics show that 55.9% of patients had experienced ≥2 moderate/severe exacerbations in the previous year, 79.1% were receiving an ICS-containing treatment at study entry, and 59.9% had blood eosinophil counts ≥150 cells/mm.
CONCLUSIONS
ETHOS will provide data on exacerbations, patient-reported outcomes, mortality, and safety in 8572 patients with moderate-to-very severe COPD receiving triple and dual fixed-dose combinations. For the first time, ICS/LAMA/LABA triple therapy with two different doses of ICS will be compared to dual ICS/LABA and LAMA/LABA therapies.
CLINICAL TRIAL REGISTRATION NUMBER
NCT02465567.
Topics: Administration, Inhalation; Adult; Aged; Aged, 80 and over; Budesonide; Drug Delivery Systems; Female; Formoterol Fumarate; Glycopyrrolate; Humans; Male; Metered Dose Inhalers; Middle Aged; Pulmonary Disease, Chronic Obstructive; Severity of Illness Index; Treatment Outcome
PubMed: 31605923
DOI: 10.1016/j.rmed.2019.08.010 -
The New England Journal of Medicine May 2018In patients with mild asthma, as-needed use of an inhaled glucocorticoid plus a fast-acting β-agonist may be an alternative to conventional treatment strategies. (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
In patients with mild asthma, as-needed use of an inhaled glucocorticoid plus a fast-acting β-agonist may be an alternative to conventional treatment strategies.
METHODS
We conducted a 52-week, double-blind trial involving patients 12 years of age or older with mild asthma. Patients were randomly assigned to one of three regimens: twice-daily placebo plus terbutaline (0.5 mg) used as needed (terbutaline group), twice-daily placebo plus budesonide-formoterol (200 μg of budesonide and 6 μg of formoterol) used as needed (budesonide-formoterol group), or twice-daily budesonide (200 μg) plus terbutaline used as needed (budesonide maintenance group). The primary objective was to investigate the superiority of as-needed budesonide-formoterol to as-needed terbutaline with regard to electronically recorded weeks with well-controlled asthma.
RESULTS
A total of 3849 patients underwent randomization, and 3836 (1277 in the terbutaline group, 1277 in the budesonide-formoterol group, and 1282 in the budesonide maintenance group) were included in the full analysis and safety data sets. With respect to the mean percentage of weeks with well-controlled asthma per patient, budesonide-formoterol was superior to terbutaline (34.4% vs. 31.1% of weeks; odds ratio, 1.14; 95% confidence interval [CI], 1.00 to 1.30; P=0.046) but inferior to budesonide maintenance therapy (34.4% and 44.4%, respectively; odds ratio, 0.64; 95% CI, 0.57 to 0.73). The annual rate of severe exacerbations was 0.20 with terbutaline, 0.07 with budesonide-formoterol, and 0.09 with budesonide maintenance therapy; the rate ratio was 0.36 (95% CI, 0.27 to 0.49) for budesonide-formoterol versus terbutaline and 0.83 (95% CI, 0.59 to 1.16) for budesonide-formoterol versus budesonide maintenance therapy. The rate of adherence in the budesonide maintenance group was 78.9%. The median metered daily dose of inhaled glucocorticoid in the budesonide-formoterol group (57 μg) was 17% of the dose in the budesonide maintenance group (340 μg).
CONCLUSIONS
In patients with mild asthma, as-needed budesonide-formoterol provided superior asthma-symptom control to as-needed terbutaline, assessed according to electronically recorded weeks with well-controlled asthma, but was inferior to budesonide maintenance therapy. Exacerbation rates with the two budesonide-containing regimens were similar and were lower than the rate with terbutaline. Budesonide-formoterol used as needed resulted in substantially lower glucocorticoid exposure than budesonide maintenance therapy. (Funded by AstraZeneca; SYGMA 1 ClinicalTrials.gov number, NCT02149199 .).
Topics: Administration, Inhalation; Adolescent; Adult; Aged; Asthma; Bronchodilator Agents; Budesonide; Child; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Female; Forced Expiratory Volume; Formoterol Fumarate; Glucocorticoids; Humans; Maintenance Chemotherapy; Male; Medication Adherence; Middle Aged; Surveys and Questionnaires; Terbutaline; Young Adult
PubMed: 29768149
DOI: 10.1056/NEJMoa1715274 -
The Journal of Allergy and Clinical... Jan 2022The use of a single inhaler containing the combination of an inhaled corticosteroid (ICS) and formoterol, a specific long-acting bronchodilator, for both maintenance and... (Review)
Review
The use of a single inhaler containing the combination of an inhaled corticosteroid (ICS) and formoterol, a specific long-acting bronchodilator, for both maintenance and quick relief therapy (single maintenance and reliever therapy [SMART or MART]) is recommended by both the Global Initiative for Asthma and the National Asthma Education and Prevention Program Coordinating Committee in steps 3 and 4 of asthma management. This article provides practical advice about implementing SMART in clinical practice based on evidence and clinical experience. Fundamental to SMART is that ICS-formoterol provides quick relief of asthma symptoms similar to that of short-acting β-agonists such as albuterol, while reducing the risk for severe asthma exacerbations and at an overall lower ICS exposure. Most SMART clinical trials were in adults and adolescents (aged ≥12 years), using budesonide-formoterol 160/4.5 μg (delivered dose), one inhalation once or twice daily (step 3) and two inhalations twice daily (step 4). For both steps 3 and 4, patients take additional inhalations of budesonide-formoterol 160/4.5 μg, one inhalation whenever needed for symptom relief, up to a maximum for adults and adolescents of 12 total inhalations in any single day (delivering 54 μg formoterol). The efficacy and safety of SMART with budesonide-formoterol and beclometasone-formoterol have been confirmed, but other ICS-long-acting bronchodilator combinations have not been studied. The SMART regimen should be introduced with a careful explanation of its role in self-management, preferably with a customized written asthma action plan. The cost to patients and the availability of SMART treatment will depend on the prescribed dose and national or local payer agreements.
Topics: Administration, Inhalation; Adolescent; Adult; Asthma; Bronchodilator Agents; Budesonide; Child; Drug Combinations; Ethanolamines; Formoterol Fumarate; Humans; Treatment Outcome
PubMed: 34666208
DOI: 10.1016/j.jaip.2021.10.011 -
International Journal of Chronic... 2023Triple therapy to prevent exacerbations from chronic obstructive pulmonary disease (COPD) is associated with improved health compared to single and dual-agent therapy in...
Exacerbations and Real-World Outcomes After Single-Inhaler Triple Therapy of Budesonide/Glycopyrrolate/Formoterol Fumarate, Among Patients with COPD: Results from the EROS (US) Study.
PURPOSE
Triple therapy to prevent exacerbations from chronic obstructive pulmonary disease (COPD) is associated with improved health compared to single and dual-agent therapy in some populations. This study assessed the benefits of prompt administration of budesonide/glycopyrrolate/formoterol fumarate (BGF) following a COPD exacerbation.
PATIENTS AND METHODS
EROS was a retrospective analysis of people with COPD using the MORE Registry. Inclusion required ≥1 severe, ≥2 moderate, or ≥1 moderate exacerbation while on other maintenance treatment. Within 12 months following the index exacerbation, ≥1 pharmacy claim for BGF was required. Primary outcomes were the rate of COPD exacerbations and healthcare costs for those that received BGF promptly (within 30 days of index exacerbation) versus delayed (31-180 days) and very delayed (181-365 days). The effect of each 30-day delay in initiation of BGF was estimated using a multivariable negative binomial regression model.
RESULTS
2409 patients were identified: 434 prompt, 1187 delayed, and 788 very delayed. The rate (95% CI) of total exacerbations post-index increased as time to BGF initiation increased: prompt 1.52 (1.39-1.66); delayed 2.00 (1.92-2.09); and very delayed 2.30 (2.20-2.40). Adjusting for patient characteristics, each 30-day delay in receiving BGF was associated with a 5% increase in the average number of subsequent exacerbations (rate ratio, 95% CI: 1.05, 1.01-1.08; <0.05). Prompt initiation of BGF was also associated with lower post-index annualized COPD-related costs ($5002 for prompt vs $7639 and $8724 for the delayed and very delayed groups, respectively).
CONCLUSION
Following a COPD exacerbation, promptly initiating BGF was associated with a reduction in subsequent exacerbations and reduced healthcare utilization and costs.
Topics: Humans; Bronchodilator Agents; Glycopyrrolate; Formoterol Fumarate; Retrospective Studies; Drug Combinations; Metered Dose Inhalers; Pulmonary Disease, Chronic Obstructive; Double-Blind Method; Budesonide; Nebulizers and Vaporizers; Administration, Inhalation
PubMed: 37849918
DOI: 10.2147/COPD.S432963 -
The New England Journal of Medicine May 2019In double-blind, placebo-controlled trials, budesonide-formoterol used on an as-needed basis resulted in a lower risk of severe exacerbation of asthma than as-needed use... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
In double-blind, placebo-controlled trials, budesonide-formoterol used on an as-needed basis resulted in a lower risk of severe exacerbation of asthma than as-needed use of a short-acting β-agonist (SABA); the risk was similar to that of budesonide maintenance therapy plus as-needed SABA. The availability of data from clinical trials designed to better reflect clinical practice would be beneficial.
METHODS
We conducted a 52-week, randomized, open-label, parallel-group, controlled trial involving adults with mild asthma. Patients were randomly assigned to one of three treatment groups: albuterol (100 μg, two inhalations from a pressurized metered-dose inhaler as needed for asthma symptoms) (albuterol group); budesonide (200 μg, one inhalation through a Turbuhaler twice daily) plus as-needed albuterol (budesonide maintenance group); or budesonide-formoterol (200 μg of budesonide and 6 μg of formoterol, one inhalation through a Turbuhaler as needed) (budesonide-formoterol group). Electronic monitoring of inhalers was used to measure medication use. The primary outcome was the annualized rate of asthma exacerbations.
RESULTS
The analysis included 668 of 675 patients who underwent randomization. The annualized exacerbation rate in the budesonide-formoterol group was lower than that in the albuterol group (absolute rate, 0.195 vs. 0.400; relative rate, 0.49; 95% confidence interval [CI], 0.33 to 0.72; P<0.001) and did not differ significantly from the rate in the budesonide maintenance group (absolute rate, 0.195 in the budesonide-formoterol group vs. 0.175 in the budesonide maintenance group; relative rate, 1.12; 95% CI, 0.70 to 1.79; P = 0.65). The number of severe exacerbations was lower in the budesonide-formoterol group than in both the albuterol group (9 vs. 23; relative risk, 0.40; 95% CI, 0.18 to 0.86) and the budesonide maintenance group (9 vs. 21; relative risk, 0.44; 95% CI, 0.20 to 0.96). The mean (±SD) dose of inhaled budesonide was 107±109 μg per day in the budesonide-formoterol group and 222±113 μg per day in the budesonide maintenance group. The incidence and type of adverse events reported were consistent with those in previous trials and with reports in clinical use.
CONCLUSIONS
In an open-label trial involving adults with mild asthma, budesonide-formoterol used as needed was superior to albuterol used as needed for the prevention of asthma exacerbations. (Funded by AstraZeneca and the Health Research Council of New Zealand; Novel START Australian New Zealand Clinical Trials Registry number, ACTRN12615000999538.).
Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Adult; Aged; Albuterol; Asthma; Bronchodilator Agents; Budesonide; Drug Therapy, Combination; Female; Formoterol Fumarate; Humans; Male; Metered Dose Inhalers; Middle Aged
PubMed: 31112386
DOI: 10.1056/NEJMoa1901963