Generic Trimbow 172micrograms/dose / 5micrograms/dose / 9micrograms/dose inhaler CFC free

BACKGROUND: The benefits of triple therapy for Chronic Obstructive Pulmonary Disease (COPD) have been established in two 52-week phase-3 randomized controlled trials. The current systematic literature review (SLR) appraised available evidence on the real-world outcomes of single-inhaler triple therapy (SITT) when prescribed by general practitioners (GPs).METHODS: Using the PICOS (Population, Intervention, Comparator, Study design) framework, a literature search was conducted to identify suitable studies for the review. PubMed and Embase databases were searched, and Rayyan was used to screen articles for inclusion. The study selection followed the Preferred Reporting Items for Systematic Reviews andMeta-Analysis guidelines.RESULTS: 1,379 non-randomized clinical studies published between 2020 and 2024 were identified from the literature search. 1,367 articles were later excluded from the review (duplicates: n = 119; not eligible: n = 1,248), leaving 12 studies for inclusion. 10 studies were single-armed, while 2 were comparative. 7 studies were from Germany, 3 from the United Kingdom, and 1 each from France, Greece, and Belgium. The SITT combinations studied were beclomethasone dipropionate/formoterol fumarate/glycopyrronium bromide (n = 9) and fluticasone furoate/umeclidinium bromide/vilanterol (n = 3). One study did not specify this. One study reported on inhaler use, 8 on adherence, 2 on drug persistence, 5 on lung function, 3 on exacerbations, and 6 on health-related quality of life.CONCLUSIONS: We found evidence of possible benefits for SITT prescribed by GPs on real-world outcomes. Nevertheless, the evidence is limited in quantity and quality, and future real-world studies need to confirm our findings.

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Recent literature has shown that triple therapy is more effective than dual therapy for individuals with uncontrolled asthma. However, the comparative efficacy between different triple therapies remains unclear. The objective of this study was to determine the comparative efficacy of extra-fine single-inhaler medium-dose (MD) or high-dose (HD) of beclometasone/formoterol/glycopyrronium bromide (BDP/FOR/GLY) compared to other triple therapies in patients whose asthma remains uncontrolled with MD or HD inhaled corticosteroids and long-acting β2-agonists. A systematic literature review identified randomized control trials on adult patients with uncontrolled asthma. Two separate networks were constructed according to patients' previous inhaled-corticosteroid dosage. Network meta-analyses evaluated severe and moderate-to-severe exacerbations, pre-dose forced expiratory volume, and asthma control questionnaire responses at 52 (± 3) weeks. Among single-inhaler triple therapies, MD BDP/FOR/GLY significantly reduced the risk of severe exacerbations (RR [95% CrI] compared to MD fluticasone/umeclidinium/vilanterol: 0.65 [0.49, 0.89]), while HD BDP/FOR/GLY demonstrated an improved trend in reducing severe and moderate-to-severe exacerbations versus HD indacaterol acetate/glycopyrronium bromide/mometasone, fluticasone/umeclidinium/vilanterol, and salmeterol/fluticasone + tiotropium. HD BDP/FOR/GLY and HD BDP/FOR + tiotropium did not differ significantly. Compared to relevant single-inhaler triple therapies, MD and HD BDP/FOR/GLY are associated with a significant benefit or trend for improvement in terms of reducing the rate of severe and moderate-to-severe exacerbations.

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BACKGROUND: In patients with asthma uncontrolled by a medium or high-strength (MS/HS) inhaled corticosteroid (ICS) plus long-acting β2-agonist (LABA), according to Global Initiative for Asthma (GINA) guidelines, a maintenance therapy option is the addition of a long-acting muscarinic antagonist (LAMA) via single-inhaler triple therapy (SITT). Evidence has previously been published on the cost-effectiveness of a SITT extra fine formulation of beclomethasone, formoterol and glycopyrronium bromide (BDP/FOR/GLY) vs. dual ICS/LABA combination, using data from two 52-week clinical trials (TRIMARAN and TRIGGER). However, there is limited evidence on the comparative cost-effectiveness of SITTs. The current analysis evaluated the cost-effectiveness of BDP/FOR/GLY versus other SITTs, in the UK setting. METHODS: Markov cohort state-transition model was developed to investigate the cost-effectiveness of BDP/FOR/GLY Medium Strength (MS) vs. fluticasone, umeclidinium, and vilanterol (FF/UMEC/VI) MS and, BDP/FOR/GLY High Strength vs. FF/UMEC/VI HS and vs. indacaterol acetate, glycopyrronium bromide, and mometasone (IND/GLY/MF) HS. A network meta-analysis was performed to estimate comparative efficacy of BDP/FOR/GLY against other SITTs. The model analyzed cost, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER), net monetary benefit (NMB), and was developed from the perspective of England National Health Service (NHS) and Prescribed Specialized Services expenditure (2022 costs). Uncertainty of the inputs was estimated using one-way and probabilistic sensitivity analyses. RESULTS: BDP/FOR/GLY MS was projected to be a dominant treatment alternative against FF/UMEC/VI MS (£5,121 less costly, gained 0.065 additional QALYs). Similarly, BDP/FOR/GLY HS was a dominant treatment alternative against FF/UMEC/VI HS (£143, 0.003 additional QALYs) and IND/GLY/MF HS (£692 less costly, gained 0.023 additional QALYs). BDP/FOR/GLY MS and HS had 77.1%, 51.3%, and 61.2% likelihoods to be cost-effective vs. FF/UMEC/VI MS, FF/UMEC/VI HS, and IND/GLY/MF HS at the defined willingness-to-pay (WTP) threshold of £20,000 per QALY gained, respectively. CONCLUSIONS: BDP/FOR/GLY MS and HS were a dominant treatment alternative compared with FF/UMEC/VI, both MS and HS, and IND/GLY/MF HS in patients with asthma uncontrolled by ICS/LABA.

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BACKGROUND: The single-inhaler triple combination of beclometasone dipropionate, formoterol fumarate, and glycopyrronium (BDP/FF/G) is available for maintenance therapy of chronic obstructive pulmonary disease (COPD). Cardinal features of COPD are lung hyperinflation and reduced exercise capacity. TRIFORCE aimed to evaluate the effect of BDP/FF/G on lung hyperinflation and exercise capacity in patients with COPD. METHODS: This double-blind, randomised, active- and placebo-controlled, crossover study recruited adults with COPD aged ≥ 40 years, who were hyperinflated and symptomatic, and were receiving mono- or dual inhaled maintenance COPD therapy. In the three treatment periods, patients were randomised to receive BDP/FF/G, BDP/FF, or placebo, each for 3 weeks, with a 7-10-day washout between treatment periods. Assessments included slow inspiratory spirometry (for resting inspiratory capacity [IC]) and constant work-rate cycle ergometry (for dynamic IC and exercise endurance time). The primary objective was to compare BDP/FF/G and BDP/FF vs. placebo for resting IC at Week 3. Key secondary objectives were to compare BDP/FF/G and BDP/FF vs. placebo for dynamic IC and exercise endurance time during constant work rate cycle ergometry at Week 3. RESULTS: Of 106 patients randomised, 95 completed the study. Resting IC adjusted mean differences vs. placebo were 315 and 223 mL for BDP/FF/G and BDP/FF, respectively (p < 0.001 for both). Adjusted mean differences vs. placebo for the key secondary endpoints were: 245 mL for dynamic IC (p < 0.001) and 69.2 s for exercise endurance time (nominal p < 0.001) with BDP/FF/G, and 96 mL (p = 0.053) and 70.1 s (nominal p < 0.001) with BDP/FF. Differences between BDP/FF/G and BDP/FF for resting and dynamic IC were 92 and 149 mL (p < 0.01 for both). All three treatments were generally well tolerated, with 27.3%, 25.3% and 19.0% of patients reporting adverse events with BDP/FF/G, BDP/FF and placebo, respectively, all mild or moderate. CONCLUSIONS: In patients with COPD, BDP/FF/G provided significant and clinically relevant improvements vs. placebo and BDP/FF in static and dynamic hyperinflation, with an improvement vs. placebo in exercise endurance. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05097014), registered 27th October 2021.

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The major determinant of the decline in lung function, quality of life, and the increased mortality risk in patients with COPD is represented by severe acute exacerbations of the disease, that is, those requiring patients' hospitalization, constituting a substantial social and health care burden in terms of morbidity and medical resource utilization. Different long-term therapeutic strategies have been proposed so far in order to prevent and/or reduce the clinical and social impact of these events, the majority of which were extrapolated from trials initially focused on the effect of long-acting muscarinic antagonist and subsequently on the efficacy of long-acting β2-agonists in combination or not with inhaled corticosteroids. The option to employ all three classes of molecules combined, despite the limited amount of evidence in our possession, represents a choice currently proposed by international guidelines; however, current recommendations are often based mainly on observational studies or on the results of secondary outcomes in randomized controlled trials. The present narrative review evaluates the available trials that investigated the efficacy of inhaled therapy to prevent COPD exacerbations and especially severe ones, with a particular focus on beclomethasone dipropionate/formoterol/glycopyrronium bromide fixed dose combination, which is the first treatment that comprises all the three drug classes, specifically tested for the prevention of moderate and severe COPD exacerbations.

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Purpose: The TRITRIAL study assessed the effects of beclometasone dipropionate/formoterol fumarate/glycopyrronium (BDP/FF/G) fixed combination in patients with chronic obstructive pulmonary disease (COPD) in a real-world setting, focusing on patient's experience and perspective through the use of patients reported outcomes. Patients and Methods: TRITRIAL was a multicenter, prospective, observational study conducted on patients with moderate-severe COPD treated with BDP/FF/G fixed therapy for 12 months. The main objective was to evaluate the impact of BDP/FF/G on health status through the COPD Assessment Test (CAT) score. Additional assessments included adherence and satisfaction, measured by the TAI-10/12 questionnaire and a specifically designed eight-item questionnaire, quality of life through the EQ-5D-5L test, sleep quality through the COPD and Asthma Sleep Impact Scale (CASIS), as well as safety and disease-related outcomes. Results: Data from 655 patients were analyzed in the study. The mean total CAT score significantly improved (from 22.8 at baseline to 18.1 at 6 months and 16.5 at 12 months; p < 0.0001), as well as all the eight CAT sub-items, which decreased on average by 0.5-0.9 points during the study. Adherence and usability of the inhaler also improved during the study, with a decrease in poor compliance (from 30.1% to 18.3%) and an increase in good compliance (from 51.8% to 58.3%) according to the TAI score. Patients also benefited from significantly improved quality of life (EQ Index from 0.70 to 0.80; EQ-5D VAS score from 55.1 to 63.1) and sleep quality (CASIS score from 41.1 to 31.8). Finally, patients reported a significant reduction in exacerbation during the study. Conclusion: TRITRIAL showed that the BDP/FF/G fixed combination is effective and safe in patients with moderate-severe COPD and poorly controlled disease, improving patients' HRQoL, sleep quality, adherence and inhaler usability and reducing COPD symptoms and the risk of exacerbation in a real-life setting.

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Use of propellants with high global warming potential (such as HFA-134a) for pressurised metered-dose inhalers (pMDIs) is being phased down. Switching to dry-powder inhalers may not be clinically feasible for all patients; an alternative is reformulation using propellants with low global warming potential. The combination of beclometasone dipropionate/formoterol fumarate/glycopyrronium bromide (BDP/FF/GB) is available for asthma or chronic obstructive pulmonary disease via pMDI using HFA-134a as propellant. This is being reformulated using the low global warming potential propellant HFA-152a. This manuscript reports three studies comparing BDP/FF/GB pharmacokinetics delivered via pMDI using HFA-152a vs HFA-134a. The studies were four-way crossover, single-dose, randomised, double-blind, in healthy volunteers. In Studies 1 and 2, subjects inhaled four puffs of BDP/FF/GB (Study 1: 100/6/12.5 μg [medium-strength BDP]; Study 2: 200/6/12.5 μg [high-strength]), ingesting activated charcoal in two of the periods (once per propellant). In Study 3, subjects inhaled medium- and high-strength BDP/FF/GB using a spacer. All three studies compared HFA-152a vs HFA-134a in terms of lung availability and total systemic exposure of beclometasone-17-monopropionate (B17MP; active metabolite of BDP), BDP, formoterol and GB. Bioequivalence was concluded if the 90% confidence intervals (CIs) of the ratios between formulations of the geometric mean maximum plasma concentration (Cmax) and area under the plasma concentration–time curve between time zero and the last quantifiable timepoint (AUC0–t) for the analytes were between 80–125%. In Studies 1 and 2, systemic exposure bioequivalence (i.e., comparisons without charcoal block) was demonstrated, except for GB Cmax in Study 2 (upper 90% CI 125.11%). For lung availability (i.e., comparisons with charcoal block), B17MP and formoterol demonstrated bioequivalence in both studies, as did BDP in Study 2; in Study 1, BDP upper CIs were 126.96% for Cmax and 127.34% for AUC0–t). In Study 1, GB AUC0–t lower CI was 74.54%; in Study 2 upper limits were 135.64% for Cmax and 129.12% for AUC0–t. In Study 3, the bioequivalence criteria were met for BDP, B17MP and formoterol with both BDP/FF/GB strengths, and were met for GB AUC0–t, although not for Cmax. Both formulations were similarly well tolerated in all three studies. Overall, while formal bioequivalence cannot be concluded for all analytes, these data suggest therapeutic equivalence of the new formulation with the existing BDP/FF/GB pMDI formulation, therefore supporting reformulation using a propellant with low global warming potential.

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Purpose: COPD affects more than 300 million people worldwide, requiring inhalation treatment. Novel triple formulations of ICS, LABAs and LAMAs are becoming the mainstay of treatment, however there is still a lack of clinical evidence for personalized therapy. Patients and Methods: RATIONALE was a non-interventional, prospective, 52 week study, assessing the effectiveness of beclometasone/formoterol/glycopyrronium-bromide (BDP/FF/G), in symptomatic COPD patients, with moderate airflow obstruction. The study included 4 visits, where data on demographic parameters, exacerbations, symptoms, quality of life (based on the EQ-5D-3L questionnaire) and lung function were collected. Data on adherence to treatment, based on prescriptions filled was collected from the database of the National Health Insurance Fund, with the patients' consent. The primary objective was the change of adherence to treatment during the study, compared to baseline. Results: Altogether 613 patients had been enrolled. Their average age was 64.56 years and 50.5% were female. The average CAT score was 20.86, and most patients had suffered minimum one exacerbation (82.2%). Average FEV1 was 59.6%. Most patients had some limitation in one or more dimensions of EQ-5D-3L, with an average visual analogue scale score (VAS) of 60.31. After 12 months of treatment, adherence improved significantly - proportion of patients in the highest adherence group increased from 29.8% to 69.7% (p<0.001). The average CAT score improved by 7.02 points (95% CI 5.82-8.21, p<0.001). There was a significant improvement in all dimensions of EQ-5D-3L, with an average increase of 17.91 (95% CI 16.51-19.31, p< 0.001) points in the VAS score. Exacerbation frequency also decreased significantly. Conclusion: Although limitations of observational studies are present, we observed that early introduction of fixed triple combination results in a marked improvement in adherence to treatment, symptom scores, exacerbation frequency and quality of life. The optimal choice of treatment is crucial for reaching the highest possible adherence.

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