Triple therapy for COPD: a crude analysis from a systematic review of the evidence

Lόpez-Campos, José Luís; Carrasco‐Hernández, Laura; Quintana‐Gallego, Esther; Calero-Acuña, Carmen; Márquez-Martín, Eduardo; Ortega-Ruiz, Francisco; Soriano, Joan B.

doi:10.1177/1753466619885522

Cited by 14 publications

(10 citation statements)

References 53 publications

(88 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This can translate into clinical benefits resulting from improved patient satisfaction and compliance with FDC therapy, leading to improved glycemic control and an increased likelihood of achieving glycemic targets [19][20][21]. FDCs are increasingly used in clinical practice for a range of chronic disorders that require the use of multiple treatments, such as chronic obstructive pulmonary disease [22], hypertension [23,24], hepatitis C [25,26], and HIV infection [27,28], with the aim of simplifying treatment regimens and improving clinical outcomes. Similarly, in the field of T2D management, the use of FDCs of effective and well-tolerated therapies can offer a useful treatment option to help optimize therapy for individual patients, and several FDC therapies for T2D are available for clinical use [29].…”

Section: Introductionmentioning

confidence: 99%

Triple fixed-dose combination empagliflozin, linagliptin, and metformin for patients with type 2 diabetes

Lingvay

Beetz

Sennewald

et al. 2020

Postgraduate Medicine

View full text Add to dashboard Cite

Objectives: Fixed-dose combination (FDC) therapy can improve outcomes in type 2 diabetes (T2D). We evaluated the bioequivalence of 2 doses of an FDC of extended-release metformin (metformin XR), empagliflozin, a sodium-glucose co-transporter 2 inhibitor, and linagliptin, a dipeptidyl peptidase-4 inhibitor, versus corresponding free tablet combinations. Methods: Two randomized, open-label, two-way crossover studies in healthy adults compared: 2 FDC tablets of empagliflozin 5 mg/linagliptin 2.5 mg/metformin XR 1000 mg (Study 1; N = 30), 1 FDC tablet of empagliflozin 25 mg/linagliptin 5 mg/metformin XR 1000 mg (Study 2; N = 30) versus corresponding dose of free combinations. Subjects received study medication under fed conditions; washout was ≥35 days between treatments. Primary endpoints: area under the plasma concentration-time curve (AUC) from time 0 to last quantifiable data point for empagliflozin and metformin; AUC from time 0 to 72 hours for linagliptin, and peak plasma concentration (C max) for empagliflozin, linagliptin, and metformin. Bioequivalence was defined as adjusted geometric mean ratios (FDC: free combination) and two-sided 90% confidence intervals (CIs) of AUC and C max for each component within 80.00-125.00%. Results: Study 1: 27/29 and 28/30 treated participants were included in the pharmacokinetic analysis for the FDC and free combination periods, respectively. Study 2: 29/29 treated participants were included in the pharmacokinetic analysis for both periods. The adjusted geometric mean ratios of FDCs to their respective free tablet combinations and two-sided 90% CIs were all within the predefined range. The shapes of the mean plasma concentration-time profile of empagliflozin, linagliptin, and metformin XR were similar for subjects in the FDC and free combination groups in both studies. No serious adverse events were reported. Conclusion: The evaluated doses of empagliflozin/linagliptin/metformin XR FDC tablets were bioequivalent to the corresponding free combinations. Based on these two bioequivalence studies and existing phase 3 data, the FDA has recently approved this triple FDC to improve glycemic control in adults with T2D. PLAIN LANGUAGE SUMMARY: Study supports the convenience of empagliflozin, linagliptin, and metformin XR in 1 tablet as new treatment for type 2 diabetes What is the purpose of this summary? • This summary is to help you understand findings from recent research. • This summary is about 2 studies that are part of a larger group of studies with these medications. Researchers look at many studies to understand whether a medication works, how it works, and whether it is safe to prescribe to patients. What is known? • People with type 2 diabetes often need several medicines to control their blood sugar. • Some people find it difficult to take a lot of different tablets, and some people may not want to. This can lead to difficulties with managing type 2 diabetes. • Combining medicines into 1 tablet may help make it easier to take the treatment and to manage type 2 diabetes, wh...

show abstract

Section: Introductionmentioning

confidence: 99%

Triple fixed-dose combination empagliflozin, linagliptin, and metformin for patients with type 2 diabetes

Lingvay

Beetz

Sennewald

et al. 2020

Postgraduate Medicine

View full text Add to dashboard Cite

show abstract

“…In fact, evidence demonstrating a better response to ICS with increased blood eosinophils comes from post hoc, pre-specified secondary and data modelling analyses, whereas no consistent relationship has been found in observational studies. 1 , 80 Moreover, neither the Food and Drug Administration nor the European Medicines Agency recommend the use of blood eosinophils in patients with COPD. 45 …”

Section: Discussionmentioning

confidence: 99%

Beyond Dual Bronchodilation – Triple Therapy, When and Why

Cazzola¹,

Rogliani²,

Laitano³

et al. 2022

COPD

View full text Add to dashboard Cite

Although pharmacological treatment of COPD is codified in different guidelines and strategy documents, there is abundant evidence of discrepancy between what they suggest and what health professionals prescribe, especially in low-risk groups where there is widespread overprescription of triple therapy. It is therefore necessary to clarify when the use of triple therapy is indicated in COPD patients and when it is preferable to maintain treatment with dual bronchodilation. In this article, we discuss our views based on our experience and what is reported in the literature and try to give answers to these two questions. The evidence generated by pivotal RCTs supports the use of triple therapy in patients who present for the first time and have severe airway obstruction, are symptomatic, have had frequent moderate or severe exacerbations in the previous year, and have peripheral eosinophilia. However, it is difficult to determine whether step-up is useful in all other cases because the available data are quite conflicting. It is likely that the inconsistency in the information generated by the various available studies may explain the prescribing behaviour of many physicians who do not adhere to recommendations of guidelines and strategies. However, it is necessary to establish whether and when the addition of an ICS to the LAMA/LABA combination is effective, to determine whether triple therapy can induce an additional clinical benefit over dual bronchodilation, irrespective of a preventive effect on COPD exacerbations, to establish its value, and to examine whether cost differences can support the use of triple therapy over combined LAMA/LABA therapy in real life.

show abstract

“…A number of systematic literature reviews and meta-analyses have been published which attempt indirect comparisons of triple therapies in patients with COPD (either single-or multiple-inhaler); in these evaluations the effects of triple therapies seem broadly consistent, but are hindered by differences in study design and the populations recruited. [32][33][34] Thirdly, as data were obtained from a database with no patients specifically recruited for the study, data on their disease characteristics are limited to lung function, and we have no information on their medication. Finally, this study involved two different sets of molecules, delivered from two different inhaler types, and so comparisons should be made with care.…”

Section: Discussionmentioning

confidence: 99%

<p>Airway Deposition of Extrafine Inhaled Triple Therapy in Patients with COPD: A Model Approach Based on Functional Respiratory Imaging Computer Simulations</p>

Usmani

Scichilone²,

Mignot³

et al. 2020

COPD

View full text Add to dashboard Cite

Introduction There is a clear correlation between small airways dysfunction and poor clinical outcomes in patients with chronic obstructive pulmonary disease (COPD), and it is therefore important that inhalation therapy (both bronchodilator and anti-inflammatory) can deposit in the small airways. Two single-inhaler triple therapy (SITT) combinations are currently approved for the maintenance treatment of COPD: extrafine formulation beclomethasone dipropionate/formoterol fumarate/glycopyrronium bromide (BDP/FF/GB), and non-extrafine formulation fluticasone furoate/vilanterol/umeclidinium (FluF/VI/UMEC). This study evaluated the lung deposition of the inhaled corticosteroid (ICS), long-acting β 2 -agonist (LABA), and long-acting muscarinic antagonist (LAMA) components of these two SITTs. Materials and Methods Lung deposition was estimated in-silico using functional respiratory imaging, a validated technique that uses aerosol delivery performance profiles, patients’ high-resolution computed tomography (HRCT) lung scans, and patient-derived inhalation profiles to simulate aerosol lung deposition. Results HRCT scan data from 20 patients with COPD were included in these analyses, who had post-bronchodilator forced expiratory volume in 1 second (FEV 1 ) ranging from 19.3% to 66.0% predicted. For intrathoracic deposition (as a percentage of the emitted dose), deposition of the ICS component was higher from BDP/FF/GB than FluF/VI/UMEC; the two triple therapies had similar performance for both the LABA component and the LAMA component. Peripheral deposition of all three components was higher with BDP/FF/GB than FluF/VI/UMEC. Furthermore, the ratios of central to peripheral deposition for all three components of BDP/FF/GB were <1, indicating greater peripheral than central deposition (0.48±0.13, 0.48±0.13 and 0.49±0.13 for BDP, FF and GB, respectively; 1.96±0.84, 0.97±0.34 and 1.20±0.48 for FluF, VI and UMEC, respectively). Conclusions Peripheral (small airways) deposition of all three components (ICS, LABA, and LAMA) was higher from BDP/FF/GB than from FluF/VI/UMEC, based on profiles from patients with moderate to very severe COPD. This is consistent with the extrafine formulation of BDP/FF/GB.

show abstract

Triple therapy for COPD: a crude analysis from a systematic review of the evidence

Cited by 14 publications

References 53 publications

Triple fixed-dose combination empagliflozin, linagliptin, and metformin for patients with type 2 diabetes

Triple fixed-dose combination empagliflozin, linagliptin, and metformin for patients with type 2 diabetes

Beyond Dual Bronchodilation – Triple Therapy, When and Why

<p>Airway Deposition of Extrafine Inhaled Triple Therapy in Patients with COPD: A Model Approach Based on Functional Respiratory Imaging Computer Simulations</p>

Contact Info

Product

Resources

About