Triple-Therapy Trials for Chronic Obstructive Pulmonary Disease: Methodological Considerations in the Mortality Effect.
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SUBMITTER: Lopez-Campos JL
PROVIDER: S-EPMC8017588 | biostudies-literature | 2021 Apr
REPOSITORIES: biostudies-literature
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Triple-Therapy Trials for Chronic Obstructive Pulmonary Disease: Methodological Considerations in the Mortality Effect.
López-Campos José Luis JL Fernández-Villar Alberto A Ruano-Ravina Alberto A
American journal of respiratory and critical care medicine 20210401 7
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Project description: Not available
| S-EPMC8017567 | biostudies-literature
Project description:Previous clinical audits for chronic obstructive pulmonary disease (COPD) have provided valuable information on the clinical care delivered to patients admitted to medical wards because of COPD exacerbations. However, clinical audits of COPD in an outpatient setting are scarce and no methodological guidelines are currently available. Based on our previous experience, herein we describe a clinical audit for COPD patients in specialized outpatient clinics with the overall goal of establishing a potential methodological workflow.A pilot clinical audit of COPD patients referred to respiratory outpatient clinics in the region of Andalusia, Spain (over 8 million inhabitants), was performed. The audit took place between October 2013 and September 2014, and 10 centers (20% of all public hospitals) were invited to participate. Cases with an established diagnosis of COPD based on risk factors, clinical symptoms, and a post-bronchodilator FEV1/FVC ratio of less than 0.70 were deemed eligible. The usefulness of formally scheduled regular follow-up visits was assessed. Two different databases (resources and clinical database) were constructed. Assessments were planned over a year divided by 4 three-month periods, with the goal of determining seasonal-related changes. Exacerbations and survival served as the main endpoints.This paper describes a methodological framework for conducting a clinical audit of COPD patients in an outpatient setting. Results from such audits can guide health information systems development and implementation in real-world settings.
| S-EPMC4636163 | biostudies-other
Project description: Not available
| S-EPMC8280091 | biostudies-literature
Project description:PurposeIn the Withdrawal of Inhaled Steroids during Optimized Bronchodilator Management (WISDOM) trial, inhaled corticosteroid (ICS) withdrawal in patients with chronic obstructive pulmonary disease receiving triple therapy (long-acting β2-agonist+long-acting muscarinic antagonist+ICS) did not change moderate/severe exacerbation risk. However, many patients were not taking triple therapy before study participation. This analysis was conducted to eliminate the impact of non-ICS users on WISDOM results by re-analyzing the data using only the subset of patients who were taking triple therapy at screening.Patients and methodsThe effect of ICS withdrawal on moderate/severe exacerbation risk in the subgroup of WISDOM patients taking triple therapy before enrolling in the study was evaluated in this post hoc analysis. Additionally, the effect of ICS withdrawal in patients with a history of ≥2 exacerbations in the previous year and various blood eosinophil counts was assessed.ResultsOverall, 39.0% (n=970: ICS continuation, 479; ICS withdrawal, 491) of the WISDOM trial population were taking triple therapy at screening. Baseline characteristics were generally similar between groups. Moderate/severe exacerbation risk between the ICS withdrawal and continuation groups (hazard ratio [HR], 1.05; 95% confidence interval [CI]: 0.89-1.25) was not increased in patients taking triple therapy at screening versus the overall trial population (HR [95% CI]: 1.06 [0.94-1.19]). However, in patients with a history of ≥2 exacerbations, exacerbation risk (HR [95% CI]) increased nominally with blood eosinophil count from 1.07 [0.81-1.41] (≥100 cells/μL) to 1.45 [0.58-3.60] (≥400 cells/μL).ConclusionConsistent with results from the overall WISDOM trial population, ICS withdrawal did not increase exacerbation risk in patients taking triple therapy at screening. Patients with a history of frequent exacerbations and higher blood eosinophil counts could benefit from continuation of ICS-based therapy.
| S-EPMC7667507 | biostudies-literature
Project description:BACKGROUND:Guidelines recommend that treatment with a long-acting β2 agonist (LABA), a long-acting muscarinic antagonist (LAMA), and inhaled corticosteroids (ICS), i.e. triple therapy, is reserved for a select group of symptomatic patients with chronic obstructive pulmonary disease (COPD) who continue to exacerbate despite treatment with dual therapy (LABA/LAMA). A number of single-inhaler triple therapies are now available and important clinical questions remain over their role in the patient pathway. We compared the efficacy and safety of single-inhaler triple therapy to assess the magnitude of benefit and to identify patients with the best risk-benefit profile for treatment. We also evaluated and compared study designs and population characteristics to assess the strength of the evidence base. METHODS:We conducted a systematic search, from inception to December 2018, of randomised controlled trials (RCTs) of single-inhaler triple therapy in patients with COPD. The primary outcome was the annual rate of moderate and severe exacerbations. RESULTS:We identified 523 records, of which 15 reports/abstracts from six RCTs were included. Triple therapy resulted in the reduction of the annual rate of moderate or severe exacerbations in the range of 15-52% compared with LAMA/LABA, 15-35% compared to LABA/ICS and 20% compared to LAMA. The patient-based number needed to treat for the moderate or severe exacerbation outcome ranged between approximately 25-50 (preventing one patient from having an event) and the event-based number needed to treat of around 3-11 (preventing one event). The absolute benefit appeared to be greater in patients with higher eosinophil counts or historical frequency of exacerbations and ex-smokers. In the largest study, there was a significantly higher incidence of pneumonia in the triple therapy arm. There were important differences in study designs and populations impacting the interpretation of the results and indicating there would be significant heterogeneity in cross-trial comparisons. CONCLUSION:The decision to prescribe triple therapy should consider patient phenotype, magnitude of benefit and increased risk of adverse events. Future research on specific patient phenotype thresholds that can support treatment and funding decisions is now required from well-designed, robust, clinical trials. TRIAL REGISTRATION:PROSPERO #CRD42018102125 .
| S-EPMC6829989 | biostudies-literature
Project description:BackgroundIn some RCTs comparing triple therapy with dual therapy in COPD, there might be a bias resulting from the use of multiple inhaler devices. This meta-analysis included only RCTs that compared ICS/LABA/LAMA vs. LABA/LAMA or ICS/LABA using a single device.MethodsWe systematically reviewed randomized controlled trials (RCTs) of single-inhaler triple therapy in patients with COPD. We searched the PubMed, MEDLINE (OvidSP), EMBASE and Cochrane Library databases to investigate the effect of single-inhaler triple therapy in COPD. The primary end points were the effect of single-inhaler triple therapy compared with single-inhaler dual therapy on all-cause mortality, the risk of acute exacerbation of COPD (AECOPD), and some safety endpoints. The Cochrane Collaboration tool was used to assess the quality of each randomized trial and the risk of bias.ResultsA total of 25,171 patients suffering from COPD were recruited for the 6 studies. This meta-analysis indicated that single-inhaler triple therapy resulted in a significantly lower rate of all-cause mortality than LABA/LAMA FDC (risk ratio, 0.70; 95% CI 0.56-0.88). Single-inhaler triple therapy reduced the risk of exacerbation and prolonged the time to first exacerbation compared with single-inhaler dual therapy. The FEV1 increased significantly more under single-inhaler triple therapy than under ICS/LABA FDC (mean difference, 103.4 ml; 95% CI 64.65-142.15). The risk of pneumonia was, however, significantly higher with ICS/LAMA/LABA FDC than with LABA/LAMA FDC (risk ratio, 1.55; 95% CI 1.35-1.80).ConclusionsThis meta-analysis suggests that single-inhaler triple therapy is effective in reducing the risk of death of any cause and of moderate or severe exacerbation in COPD patients. However, the risk of pneumonia is higher with ICS/LAMA/LABA FDC than with LABA/LAMA FDC. Trial registration PROSPERO #CRD42020186726.
| S-EPMC8299655 | biostudies-literature
Project description:BackgroundWorldwide, chronic obstructive pulmonary disease (COPD) is a highly prevalent chronic lung disease with considerable clinical and socioeconomic impact. Pharmacologic maintenance drugs (such as bronchodilators and inhaled corticosteroids) play an important role in the treatment of COPD. The cost effectiveness of these treatments has been frequently assessed, but studies to date have largely neglected the impact of treatment sequence and the exact stage of disease in which the drugs are used in real life.ObjectiveWe aimed to systematically review recently published articles that reported the cost effectiveness of COPD maintenance treatments, with a focus on key findings, quality and methodological issues.MethodsWe performed a systematic literature search in Embase, PubMed, the UK NHS Economic Evaluation Database (NHS-EED) and EURONHEED (European Network of Health Economics Evaluation Databases) and included all relevant articles published between 2011 and 2015 in either Dutch, English or German. Main study characteristics, methods and outcomes were extracted and critically assessed. The Quality of Health Economic Studies (QHES) instrument was used as basis for quality assessment, but additional items were also addressed.ResultsThe search identified 18 recent pharmacoeconomic analyses of COPD maintenance treatments. Papers reported the cost effectiveness of long-acting muscarinic antagonist (LAMA) monotherapy (n = 6), phosphodiesterase (PDE)-4 inhibitors (n = 4), long-acting beta agonist/inhaled corticosteroid (LABA/ICS) combinations (n = 4), LABA monotherapy (n = 2) and LABA/LAMA combinations (n = 2). All but two studies were funded by the manufacturer, and all studies indicated favourable cost effectiveness; however, the number of quality-adjusted life-years (QALYs) gained was small. Less than half of the studies reported a COPD-specific outcome in addition to a generic outcome (mostly QALYs). Exacerbation and mortality rates were found to be the main drivers of cost effectiveness. According to the QHES, the quality of the studies was generally sufficient, but additional assessment revealed that most studies poorly represented the cost effectiveness of real-life medication use.ConclusionsThe majority of studies showed that pharmacologic COPD maintenance treatment is cost effective, but most studies poorly reflected real-life drug use. Consistent and COPD-specific methodology is recommended.
| S-EPMC5209411 | biostudies-literature
Project description: Not available
| S-EPMC7301727 | biostudies-literature
Project description:ObjectiveTo compare the rate of moderate to severe exacerbations between triple therapy and dual therapy or monotherapy in patients with chronic obstructive pulmonary disease (COPD).DesignSystematic review and meta-analysis of randomised controlled trials.Data sourcesPubMed, Embase, Cochrane databases, and clinical trial registries searched from inception to April 2018.Eligibility criteriaRandomised controlled trials comparing triple therapy with dual therapy or monotherapy in patients with COPD were eligible. Efficacy and safety outcomes of interest were also available.Data extraction and synthesisData were collected independently. Meta-analyses were conducted to calculate rate ratios, hazard ratios, risk ratios, and mean differences with 95% confidence intervals. Quality of evidence was summarised in accordance with GRADE methodology (grading of recommendations assessment, development, and evaluation).Results21 trials (19 publications) were included. Triple therapy consisted of a long acting muscarinic antagonist (LAMA), long acting β agonist (LABA), and inhaled corticosteroid (ICS). Triple therapy was associated with a significantly reduced rate of moderate or severe exacerbations compared with LAMA monotherapy (rate ratio 0.71, 95% confidence interval 0.60 to 0.85), LAMA and LABA (0.78, 0.70 to 0.88), and ICS and LABA (0.77, 0.66 to 0.91). Trough forced expiratory volume in 1 second (FEV1) and quality of life were favourable with triple therapy. The overall safety profile of triple therapy is reassuring, but pneumonia was significantly higher with triple therapy than with dual therapy of LAMA and LABA (relative risk 1.53, 95% confidence interval 1.25 to 1.87).ConclusionsUse of triple therapy resulted in a lower rate of moderate or severe exacerbations of COPD, better lung function, and better health related quality of life than dual therapy or monotherapy in patients with advanced COPD.Study registrationProspero CRD42018077033.
| S-EPMC6218838 | biostudies-literature
Project description:BackgroundRandomised control trials (RCTs) with strict eligibility criteria can lead to trial populations not commonly seen in clinical practice. We described the proportion of people with chronic obstructive pulmonary disease (COPD) in England eligible for RCTs investigating treatment with triple therapy.MethodsMEDLINE and Clinicaltrials.gov were searched for RCTs investigating triple therapy and eligibility criteria for each trial were extracted. Using routinely collected primary care data from Clinical Practice Research Datalink Aurum linked with Hospital Episode Statistics, we defined a population of COPD patients registered at a general practice in England, who were ≥ 40 years old, and had a history of smoking. Inclusion date was January 1, 2020. Patients who died earlier or left the general practice were excluded. Eligibility criteria for each RCT was applied to the population of COPD patients and the proportion of patients meeting each trial eligibility criteria were described.Results26 RCTs investigating triple therapy were identified from the literature. The most common eligibility criteria were post-bronchodilator FEV1% predicted 30-80%, ≥ 2 moderate/≥ 1 severe exacerbations 12-months prior, no moderate exacerbations one-month prior and no severe exacerbations three-months prior, and the use of maintenance therapy or ICS use prior to inclusion. After applying each RCT eligibility criteria to our population of 79,810 COPD patients, a median of 11.2% [interquartile range (IQR) 1.8-17.4] of patients met eligibility criteria. The most discriminatory criteria included the presence exacerbations of COPD and previous COPD related medication use with a median of 67.6% (IQR 8.5-73.4) and 63% (IQR 69.3-38.4) of COPD patients not meeting these criteria, respectively.ConclusionData from these RCTs may not be generalisable to the wider population of people with COPD seen in everyday clinical practice and real-world evidence studies are needed to supplement trials to understand effectiveness in all people with COPD.
| S-EPMC10797743 | biostudies-literature