scholarly journals Triple Therapy Versus Dual Bronchodilation and Inhaled Corticosteroids/Long-Acting β-Agonists in COPD: Accumulating Evidence from Network Meta-Analyses

2019 ◽  
Vol 5 (2) ◽  
pp. 117-126 ◽  
Author(s):  
Mario Cazzola ◽  
Luigino Calzetta ◽  
Paola Rogliani ◽  
Maria Gabriella Matera
Keyword(s):  
Triple Therapy ◽  
Clinical Benefit ◽  
Inhaled Corticosteroids ◽  
Daily Practice ◽  
Chronic Obstructive ◽  
Blood Eosinophil ◽  
Dual Bronchodilation ◽  
Long Acting ◽  
Meta Analyses

Abstract Guidelines are mainly based on evidence of well-designed randomized controlled trials (RCTs), but there are limitations to the transferability of conclusions of RCTs to usual care mainly because the patients enrolled in RCTs are selected and not representative of the population encountered in daily practice; moreover, the research environment is substantially different from that of the real world. Because of the scarcity of data generated in large unselected populations in everyday clinical practice, the possibility of using meta-analyses can be considered. Recently, several meta-analyses have attempted to clarify the role of triple therapy containing a long-acting β-agonist (LABA), a long-acting muscarinic antagonist (LAMA) and an inhaled corticosteroid (ICS) delivered from a single inhaler in chronic obstructive pulmonary disease (COPD), also considering that there is a big difference in the use of triple therapy between what is recommended by COPD guidelines or strategies and the prescriptive behaviour of clinicians. Taking into account the results of the most recent meta-analyses, we believe that triple therapy provides modest clinical benefit in the general COPD population, but in patients on LABA/LAMA combination therapy, who still experience acute exacerbations of COPD (AECOPDs) and have blood eosinophil counts ≥ 300 cells·μl−1, it is of clinical relevance. On the contrary, adding a LAMA to an ICS/LABA combination elicits relevant clinical benefit in the general COPD population, supporting the role of dual bronchodilation therapy for the treatment of COPD. The quantitative synthesis of the currently available clinical evidence seems to suggest that, in patients with COPD already on ICS/LABA combination, the therapy can be improved without an increase of cardiovascular severe adverse events (SAEs) when a LAMA is added to the combination.

Stufentherapie der COPD

2019 ◽  
Vol 144 (01) ◽  
pp. 15-20
Author(s):  
Henrik Watz ◽  
Anne Kirsten ◽  
Timm Greulich
Keyword(s):  
Inhaled Corticosteroids ◽  
Exercise Intolerance ◽  
Pharmacologic Therapy ◽  
Chronic Obstructive ◽  
Blood Eosinophil ◽  
Obstructive Pulmonary Disease ◽  
Dual Bronchodilation ◽  
Related Quality ◽  
Health Related ◽  
Long Acting

AbstractThe goal of pharmacologic therapy of stable chronic obstructive pulmonary disease (COPD) is to reduce symptoms, improve exercise intolerance and health-related quality of life, and to reduce exacerbations. Inhaled long-acting β2-agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) are equally effective for the symptomatic management of COPD. However, LAMAs are more effective than LABAs in the reduction of exacerbations. In patients with symptomatic COPD pharmacologic therapy is usually escalated using the fixed combination of LAMAs and LABAs (dual bronchodilation), which is also superior to LAMA monotherapy in the prevention of exacerbations. Adding inhaled corticosteroids (ICS) to LABA and LAMA (triple therapy) for a prevention of exacerbations results in a further reduction of exacerbations, especially in those patients with higher blood eosinophil counts. Non-pharmacologic management of COPD patients includes smoking cessation programs, vaccination, pulmonary rehabilitation, and strategies to improve or maintain their physical activity.

scholarly journals Withdrawal of inhaled corticosteroids in COPD: a European Respiratory Society guideline

2020 ◽  
Vol 55 (6) ◽  
pp. 2000351 ◽  
Author(s):  
James D. Chalmers ◽  
Irena F. Laska ◽  
Frits M.E. Franssen ◽  
Wim Janssens ◽  
Ian Pavord ◽  
...  
Keyword(s):  
Inhaled Corticosteroids ◽  
Evidence Synthesis ◽  
Chronic Obstructive ◽  
Blood Eosinophil ◽  
European Respiratory Society ◽  
Obstructive Pulmonary Disease ◽  
Strong Recommendation ◽  
Assessment Development ◽  
Evaluation Approach ◽  
Long Acting

Inhaled corticosteroids (ICS) combined with bronchodilators can reduce the frequency of exacerbations in some patients with chronic obstructive pulmonary disease (COPD). There is evidence, however, that ICS are frequently used in patients where their benefit has not been established. Therefore, there is a need for a personalised approach to the use of ICS in COPD and to consider withdrawal of ICS in patients without a clear indication. This document reports European Respiratory Society recommendations regarding ICS withdrawal in patients with COPD.Comprehensive evidence synthesis was performed to summarise all available evidence relevant to the question: should ICS be withdrawn in patients with COPD? The evidence was appraised using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach and the results were summarised in evidence profiles. The evidence synthesis was discussed and recommendations formulated by a committee with expertise in COPD and guideline methodology.After considering the balance of desirable and undesirable consequences, quality of evidence, and feasibility and acceptability of interventions, the guideline panel made: 1) conditional recommendation for the withdrawal of ICS in patients with COPD without a history of frequent exacerbations, 2) strong recommendation not to withdraw ICS in patients with blood eosinophil counts ≥300 eosinophils·µL−1 and 3) strong recommendation to treat with one or two long-acting bronchodilators if ICS are withdrawn.A conditional recommendation indicates that there was uncertainty about the balance of desirable and undesirable consequences of the intervention, and that well-informed patients may make different choices regarding whether to have or not have the specific intervention.

scholarly journals Individual trajectory-based care for COPD: getting closer, but not there yet

2021 ◽  
pp. 00451-2021
Author(s):  
Nicolas Roche ◽  
Philippe Devillier ◽  
Patrick Berger ◽  
Arnaud Bourdin ◽  
Daniel Dusser ◽  
...  
Keyword(s):  
Inhaled Corticosteroids ◽  
Clinical Symptoms ◽  
Pharmacological Therapy ◽  
Response To Therapy ◽  
Treatment Preference ◽  
Chronic Obstructive ◽  
Blood Eosinophil ◽  
Close Monitoring ◽  
Obstructive Pulmonary Disease ◽  
Long Acting

Chronic obstructive pulmonary disease (COPD) is a main cause of death due to interplaying factors, including comorbidities that interfere with symptoms and response to therapy. It is now admitted that COPD management should be based on clinical symptoms and health status, and should consider the heterogeneity of patients’ phenotypes and treatable traits. This precision medicine approach involves a regular assessment of the patient's status and of expected benefits and risks of therapy. The cornerstone of COPD pharmacological therapy is inhaled long-acting bronchodilation. In patients with persistent or worsened symptoms, factors likely to interfere with treatment efficacy include the patient's non-adherence to therapy, treatment preference, inhaler misuse and/or comorbidities, which should be systematically sought before escalation is considered. Several comorbidities are known to impact symptoms, activity and lung function in vicious circles. The possible long-term risks of inhaled corticosteroids contrasting with their over-prescription in COPD patients justify the regular assessment of their benefits and risks, and de-escalation under close monitoring after a sufficient period of stability is to be considered. While commonly used in clinical trials, the relevance of routine blood eosinophil counts to guide therapy adjustment is not fully clarified. Patients’ characteristics, which define phenotypes and treatable traits and thus guide therapy, often change during life, forming the basis of the concept of clinical trajectory. The application of individual trajectory-based management of COPD in clinical practice therefore implies that the benefit:risk ratio is regularly reviewed according to the evolution of the patient's traits over time to allow optimized therapy adjustments.

scholarly journals Comparative effectiveness of triple therapy versus dual bronchodilation in COPD

2019 ◽  
Vol 5 (3) ◽  
pp. 00106-2019 ◽  
Author(s):  
Jaco Voorham ◽  
Massimo Corradi ◽  
Alberto Papi ◽  
Claus F. Vogelmeier ◽  
Dave Singh ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Triple Therapy ◽  
Real Life ◽  
Blood Eosinophil ◽  
Exacerbation Rate ◽  
Historical Cohort ◽  
Respiratory Event ◽  
Dual Bronchodilation ◽  
Exacerbation Risk ◽  
Long Acting

This real-world study compared the effectiveness of triple therapy (TT; long-acting muscarinic antagonists (LAMAs)/long-acting inhaled β-agonists (LABAs)/inhaled corticosteroids (ICSs)) versus dual bronchodilation (DB; LAMAs/LABAs) among patients with frequently exacerbating COPD. A matched historical cohort study was conducted using United Kingdom primary care data. Patients with COPD aged ≥40 years with a history of smoking were included if they initiated TT or DB from no maintenance/LAMA therapy and had two or more exacerbations in the preceding year. The primary outcome was time to first COPD exacerbation. Secondary outcomes included time to treatment failure, first acute respiratory event, and first acute oral corticosteroid (OCS) course. Potential treatment effect modifiers were investigated. In 1647 matched patients, initiation of TT reduced exacerbation risk (adjusted hazard ratio (HR) 0.87, 95% CI 0.76–0.99), risk of acute respiratory event (HR 0.74, 95% CI 0.66–0.84) and treatment failure (HR 0.83, 95% CI 0.73–0.95) compared with DB. Risk reduction for acute respiratory events was greater for patients with higher rates of previous exacerbations. At baseline blood eosinophil counts (BECs) ≥ 0.35×109 cells·L−1, TT was associated with lower risk of OCS prescriptions than DB. This study provides real-life evidence of TT being more effective in reducing exacerbation risk than DB, which became more accentuated with increasing BEC and previous exacerbation rate.

Narrative Literature Review Guided Approach of Inhaled Corticosteroid de-escalation in Chronic Obstructive Pulmonary Disease

2021 ◽  
pp. 089719002110537
Author(s):  
Anamarie Tomaich ◽  
Shawnee Klatt ◽  
Michael W. Nagy
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Inhaled Corticosteroids ◽  
Chronic Obstructive Lung Disease ◽  
Chronic Obstructive ◽  
Blood Eosinophil ◽  
Inhaled Corticosteroid ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Long Acting

Objective To review the 2020 Global Initiative for Chronic Obstructive Lung Disease (GOLD) report recommendations and create an algorithm to assist clinicians in determining which chronic obstructive pulmonary disease (COPD) patients qualify for inhaled corticosteroid (ICS) de-escalation. Data Sources: A literature search of MEDLINE/PubMed from 2002 to August 2021 was conducted using the search terms inhaled corticosteroids, chronic obstructive pulmonary disease, and de-escalation and review of the reference lists of identified articles for pertinent citations. Study Selection and Data Extraction Relevant studies and articles were included if they focused on the utilization of ICS in COPD. Data Synthesis The 2020 GOLD report only recommends triple therapy with ICS, long acting beta agonists, and long acting muscarinic antagonists for patients with frequent exacerbations, frequent hospitalizations, or elevated blood eosinophil counts. Despite this clear framework, patients are prescribed ICS without these characteristics. Available evidence suggests that these patients can be de-escalated from ICS therapy without concern for worsening lung function or exacerbations. Relevance to Patient Care and Clinical Practice: Patients with COPD may be experiencing more risk than benefit on ICS therapy. Clinicians should be knowledgeable on how to evaluate patient therapy for appropriateness and know how to safely deprescribe ICS given their limited efficacy in many COPD patients. Conclusion There remains no specific guidance on how to de-escalate patients off an ICS when the therapy is not indicated. Use of clinical evidence with stepwise algorithms can be models to approach de-escalation of ICS in patients with COPD.

scholarly journals Escalation Time to Open Triple Combination Therapy from the Initiation of LAMA versus ICS/LABA in COPD Management: Findings from Comparing the Incidence of Tiotropium and ICS/LABA in Real-World Use in South Korea (CITRUS) Study

2021 ◽  
Vol 11 (12) ◽  
pp. 1325
Author(s):  
Ye Jin Lee ◽  
Chin Kook Rhee ◽  
Yong Il Hwang ◽  
Kwang Ha Yoo ◽  
So Eun Lee ◽  
...  
Keyword(s):  
Combination Therapy ◽  
South Korea ◽  
Triple Therapy ◽  
Inhaled Corticosteroids ◽  
Chronic Obstructive ◽  
Triple Combination ◽  
Obstructive Pulmonary Disease ◽  
Triple Combination Therapy ◽  
Copd Patients ◽  
Long Acting

Background: bronchodilators are the key treatment for chronic obstructive pulmonary disease (COPD), however, inhaled corticosteroids (ICSs)/long-acting β2-agonists (LABA) are widely prescribed. We compared the escalation time to open triple combination therapy between long-acting muscarinic receptor antagonists (LAMA) and ICS/LABA in COPD management. Methods: this retrospective study included COPD patients selected from the National Health Insurance Service of South Korea from January 2005 to April 2015. The primary outcome was the escalation time to triple therapy in patients who initially received LAMA or ICS/LABA. Other outcomes included risk factors predisposing escalation to triple combination therapy. Results: a total of 2444 patients were assigned to the LAMA or ICS/LABA groups. The incidences of triple combination therapy in the LAMA and ICS/LABA groups were 81.0 and 139.8 per 1000 person-years, respectively (p < 0.001); the median times to triple therapy escalation were 281 and 207 days, respectively (p = 0.03). Treatment with ICS/LABA showed a higher risk of triple therapy escalation compared to LAMA (hazard ratio (HR), 1.601; 95% confidence interval (CI), 1.402–1.829). The associated risk factor was male sex. (HR, 1.564; 95% CI, 1.352–1.809). Conclusions: the initiation of COPD treatment with LAMA is associated with a reduced escalation time to triple therapy compared with ICS/LABA.

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

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0255545
Author(s):  
Yixuan Jiang ◽  
Hao Hu ◽  
Siu-wai Leung
Keyword(s):  
Systematic Review ◽  
Triple Therapy ◽  
Assessment Tool ◽  
Inhaled Corticosteroids ◽  
Meta Analysis ◽  
Chronic Obstructive Lung Disease ◽  
Fixed Dose ◽  
Chronic Obstructive ◽  
Bias Analysis ◽  
Long Acting

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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