Maintenance Treatment Of Chronic Obstructive Pulmonary Disease Research Articles

Ensifentrine: First Approval.

Ensifentrine, an inhaled, selective phosphodiesterase (PDE) 3 and PDE4 inhibitor, is being developed by Verona Pharma plc for the treatment of respiratory diseases, including chronic obstructive pulmonary disease (COPD). In June 2024, ensifentrine (OHTUVAYRE™) inhalation suspension was approved for the maintenance treatment of COPD in adult patients in the USA. This article summarizes the milestones in the development of ensifentrine leading to this first approval for the maintenance treatment of COPD.

Comparison of Acebrophylline vs Theophylline on Chronic Obstructive Pulmonary Disease

Over the past few decades, there has been a positive increase in the use of pharmaceutical treatment for chronic obstructive pulmonary disease (COPD). Methylamines are often used in COPD patients. Theophylline is a well-known bronchodilator and anti-inflammatory medication, and acebrophylline is a relatively recent addition to contemporary respiratory care. Both are used as adjunctive therapy for patients with stable COPD who are receiving long-acting muscarinic antagonists (LAMAs). One of the world's most pressing public health issues at the moment is chronic obstructive pulmonary disease (COPD). Oral medication therapy is utilised as a second- or third-line maintenance treatment for COPD, while inhaled treatments constitute the first-line maintenance treatment. In comparison to inhaled therapy, oral medications exhibit modest bronchodilator and anti-inflammatory properties, albeit at a lesser concentration. A number of benefits of oral medication therapy include its rapid availability, cloudiest pharmacologic methods of action, convenience of administration, lack of complications with correct inhalational drug deposition in lung airways, and cost-effectiveness.

Lack of COPD-Related Follow-Up Visits and Pharmacological Treatment in Swedish Primary and Secondary Care.

ObjectiveThe Swedish guidelines recommend that patients with chronic obstructive pulmonary disease (COPD) on maintenance treatment are monitored annually, and within six weeks after an exacerbation. We describe the patterns of COPD-related visits in Sweden, both regular follow-up and post-exacerbation visits.MethodsPatients (>40 years) with a first-time COPD diagnosis between 2006 and 2017 were identified in primary care medical records and linked to hospital contacts and administered drug data. The index date was defined as the first collection of inhaled COPD maintenance treatment after the diagnosis. Regular COPD visits within 15-months after the index, and post-exacerbation visits for COPD within six weeks and 15-months after an exacerbation were estimated using the cumulative incidence function adjusted for competing risk. Visits without a ICD code for COPD were not included in the analyses.ResultsA total of 19,857 patients (mean age 69 years, 57% females) were included. The overall probability of having a regular follow-up visit for COPD within 15 months post-index was 39.1%. In total, 15,095 (76%) patients experienced at least one COPD exacerbation during the observation period. Among them, the probability of having a post-exacerbation visit was 7.0% within six weeks and 29.7% within 15-months. Patients without a regular COPD follow-up visit claimed significantly more oral corticosteroids (25.6% vs 15.6%), more respiratory antibiotics (39.1% vs 23.1%), and less maintenance treatment (10.9% vs 16.5%).ConclusionOnly 39% of COPD patients attended a regular follow-up visit within 15-months from the COPD diagnosis and one-third had a post-exacerbation visit. The adherence to guideline recommendations need to be improved.

Therapeutic Success in Swiss COPD Patients Receiving Dual Bronchodilation Therapy as COPD Maintenance Treatment.

Health-related quality of life (HRQoL) in patients with moderate to severe chronic obstructive pulmonary disease (COPD) is often reduced by high symptom burden and frequent exacerbations. So far, data on therapeutic success in Swiss COPD patients receiving dual bronchodilation therapy as COPD maintenance treatment are limited. Data from a recently published, non-interventional study on clinical benefit after the start of combined tiotropium–olodaterol treatment were analyzed focusing on Swiss patients compared to the overall cohort including patients from various European countries. Demographic data on the changes in Clinical COPD Questionnaire (CCQ) for the assessment of HRQoL in correlation to symptoms and the number of exacerbations, as well as physician’s global assessment (PGE), were evaluated 6 weeks after treatment start. In Switzerland (n = 61), significantly more patients had comorbidities and exacerbations but showed less symptoms compared to the overall cohort (n = 4639). HRQoL improved in both cohorts, with a negative correlation to symptom burden and number of exacerbations in the overall cohort. PGE scores improved after 6 weeks with a better general condition at baseline in Swiss patients (PGE score 4/5: 68.9% [Swiss cohort] vs. 49.0% [overall cohort]. Despite significant differences regarding the presence of symptoms and exacerbations, therapeutic success was similar in both patient groups. Highly symptomatic patients benefited mostly from tiotropium–olodaterol treatment.

Budesonide/Glycopyrronium/Formoterol: A Review in COPD.

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 β2-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.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40265-021-01562-6.

First triple therapy in one inhaler for COPD patients: treatment approach (scientific data overview)

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of disability and mortality. The paper discusses the role of single inhaler triple therapy in COPD maintenance treatment. Trelegy Ellipta - the first fixed triple combination registered in Russia - is taken as an example. Below we deliberate on classes of components and their mechanism of action, clinical effectiveness, influence on exacerbations' risk, functional and patient-reported outcomes, safety, and mortality reduction. We also discuss the approaches for triple therapy administration to COPD patients recommended by a row of national and global guidelines.

Formoterol for the Treatment of Chronic Obstructive Pulmonary Disease.

Bronchodilators, including long-acting β2-agonists and long-acting muscarinic antagonists, are the mainstay for treatment of patients with chronic obstructive pulmonary disease (COPD) to prevent exacerbations or reduce symptoms. Formoterol is a highly selective and potent β2-agonist that relaxes airway smooth muscle to significantly improve lung function. Inhaled formoterol works within 5 minutes of administration and provides improvements in spirometry measurements over 12 hours. The lipophilicity of formoterol allows it to form a depot within the smooth muscle to provide a prolonged duration of action. Following therapeutic doses, plasma concentrations are very low or undetectable. Determination of the pharmacokinetics of formoterol following high-dose administration to healthy volunteers revealed that the drug was rapidly absorbed and excreted unchanged in the urine with a half-life of 10 hours. Inhaled formoterol, as monotherapy or in combination with other agents, is an effective and safe treatment option for patients with moderate to severe COPD. Clinical studies have demonstrated improvements in lung function and COPD symptoms, particularly dyspnea; reductions in the risk of exacerbations; and improvement in patients’ health status. The adverse event profile of inhaled formoterol is similar to that of placebo, with few adverse cardiovascular events. Formoterol is a valuable bronchodilator used in the maintenance treatment of COPD. This review describes the mechanism of action, pharmacodynamics, and pharmacokinetics of inhaled formoterol. It also reviews the results of large, randomized, controlled clinical trials that evaluated the use of formoterol as monotherapy and in combination with inhaled corticosteroids, long-acting muscarinic antagonists, and triple therapy regimens in the treatment of patients with moderate to severe COPD.

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

IntroductionThere 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 β2-agonist (LABA), and long-acting muscarinic antagonist (LAMA) components of these two SITTs.Materials and MethodsLung 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.ResultsHRCT scan data from 20 patients with COPD were included in these analyses, who had post-bronchodilator forced expiratory volume in 1 second (FEV1) 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).ConclusionsPeripheral (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.

Theophylline and Leukotriene Modifiers: Is There Any Compelling Role in COPD?

Chronic obstructive pulmonary disease (COPD) is considered to be an emerging global public health problem. Inhaled therapies are first-line maintenance treatment for COPD, whereas oral drug therapies are used as second or third line maintenance treatment. Oral drugs have modest bronchodilatory as well as anti-inflammatory activities but have lower potency as compared to inhaled therapies. Oral drug therapy can play an important role with several advantages that include distinctive pharmacologic mechanisms of action, prompt availability, ease of administration without the challenges of proper inhalational drug deposition in airways of lung and cost-effectiveness. Theophyllines and leukotriene modifiers are frequently prescribed oral drug therapies worldwide. Although evidence remains weak regarding the exact role of theophyllines in COPD, they are still used alone or as an add-on agent to inhaled therapies but at the expense of narrow therapeutic index leading to dose-dependent toxicities. Leukotriene modifiers are currently prescribed as add-on agents to inhaled therapies in moderate-to-severe asthma. However, the role of leukotriene modifiers in COPD is not very convincing with limited evidence. Overall, there is not any compelling evidence on the utility of theophyllines and leukotriene modifiers in the management of COPD.

PROFILE OF STABLE COPD PATIENTS IN COUNTRIES FROM CENTRAL EASTERN EUROPE: RESULTS FROM A LARGE OBSERVATIONAL STUDY

SESSION TITLE: Tuesday Abstract Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/22/2019 01:00 PM - 02:00 PM PURPOSE: The profile of patients with stable chronic obstructive pulmonary disease (COPD) in countries from Central Eastern Europe (CEE) is not clearly characterized. The population of stable COPD patients from 5 CEE countries participating in a large cross-sectional observational study is described here. METHODS: In a multinational study (NCT03031769), 2162 patients with stable COPD were enrolled from in 11 participating countries. In total, 1422 patients were enrolled from CEE: Romania (RO) n=406, Poland (PL) n=356, Serbia (SB) n=250, Bulgaria (BG) n=210 and Slovakia (SK) n=200. Eligible patients were aged ≥40 years with ≥1 year since COPD diagnosis. All patients were current or former smokers with a smoking history of ≥10 pack-years (PY). Stable disease was defined as no exacerbation history or changes in COPD maintenance treatment in last 2 months before enrolment. Exacerbation was defined as acute worsening of respiratory symptoms resulting in additional therapy. RESULTS: The mean age was 65.9 years in RO, 66.6 in SK, 66.7 in BG, 67.0 in PL and 68.0 in SB. More males were enrolled, from 61.0% in PL to 78.5% in SK and 83.5% in RO. Mean tobacco consumption (PY) for both smokers and non-smokers was 32.2 in BG, 32.5 in SK, 36.4 in PL, 38.1 in RO and 41.9 in SB. Mean post-bronchodilator FEV1 varied from 45.0% in BG and 47.8% in RO to 54.1% in PL, 54.5% in SK and 60.7% in SB. Most patients had moderate to severe airflow obstruction – percentages of patients ranged from 80.0% in SB, 83.7% in RO, 84.3% in BG, 87.7% in PL and 90.0% in SK. Mean number of exacerbations/patient in the last year (mild, moderate and severe) was 0.7 in SK, 1.9 in RO, 3.5 in BG, 4.8 in PL and 6.3 in SB. SB had the highest percentage of patients reporting severe exacerbations in last year (58.8%), while BG had highest percentage of patients with moderate exacerbations in last year (51.4%). Mean number of visits/year to chest specialist was 2.3 in BG, 3.4 in RO, 3.5 in SB, 3.7 in PL and 4.7 in SK. Mean score of COPD Assessment Test (CAT) ranged from 15 in SK and SB to almost 17 in PL, 19 in RO and 19.2 in BG. The distribution of low burden (A/C) vs. high burden (B/D) symptom categories by GOLD 2017 report differed at country level: 27.2% vs. 72.8% in BG, 35.9% vs. 64.1% in PL, 27.6% vs. 72.4% in RO, 32.5% vs. 67.5% in SK and 48.4% vs. 51.6% in SB. CONCLUSIONS: More discrepancies than similarities in characteristics of stable COPD patients were found across CEE countries participating in this study. The cultural, environmental and healthcare system differences may partly explain the results found. CLINICAL IMPLICATIONS: This large study allowed the homogeneous collection of data from 5 CEE countries. The variability of characteristics of stable COPD patients across countries may be explained by personal factors and local treatment and monitoring aspects that require further exploration. DISCLOSURES: Employee relationship with AstraZeneca Please note: $1001 - $5000 Added 03/10/2019 by Silviu Alecu, source=Web Response, value=Salary No relevant relationships by Adam Antczak, source=Web Response Employee relationship with AstraZeneca Please note: $1001 - $5000 Added 03/14/2019 by Yunqin Chen, source=Web Response, value=Salary No relevant relationships by Florin Mihaltan, source=Web Response No relevant relationships by Vesna Radulović, source=Web Response

BURDEN OF RESPIRATORY SYMPTOMS IN STABLE COPD PATIENTS FROM CENTRAL EASTERN EUROPE: RESULTS FROM A LARGE OBSERVATIONAL STUDY

SESSION TITLE: Wednesday Electronic Posters 2 SESSION TYPE: Original Inv Poster Discussion PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM PURPOSE: Since 2011, the Global Initiative for Obstructive Lung Disease (GOLD) has included symptom burden in the multidimensional assessment of patients with chronic obstructive pulmonary disease (COPD). The prevalence and severity of 24-hour respiratory symptoms in COPD patients from Central Eastern Europe (CEE) is less known. METHODS: This was a multinational cross-sectional study (NCT03031769) in stable COPD patients from 11 countries. Out of 2162 patients enrolled, 1422 were from 5 CEE countries: Romania (RO) n=406, Poland (PL) n=356, Serbia (SB) n=250, Bulgaria (BG) n=210, and Slovakia (SK) n=200. All patients had COPD with duration of at least 1 year. Stable disease was defined as no exacerbation history or changes in maintenance treatment in the last 2 months before enrolment. Respiratory symptoms over the last 24 hours were evaluated using specific questionnaires: Night-time Symptoms of COPD Instrument-NiSCI, Early Morning Symptoms of COPD Instrument-EmSCI and the derivative questionnaire for stable patients from Evaluating Respiratory Symptoms in COPD (E-RS™:COPD) for daytime symptoms. COPD Assessment Test (CAT) was also used. RESULTS: The percentages of patients reporting at least one respiratory symptom in each period of the day in each country were as follows. Night-time (NT) symptoms: BG 84.8%, PL 61.8%, RO 71.4%, SK 77.5%, SB 66.8%; early morning (EM) symptoms: BG 93.8%, PL 89.6%, RO 87.7%, SK 92.0%, SB 80.4%; day-time (DT) symptoms: BG 99.5%, PL 94.7%, RO 92.6%, SK 95.5%, SB 90.8%. Across countries, mean severity scores between 0.6 and 1 for NT and between 0.8 and 1.1 for EM indicated mild symptoms. Mean severity scores for DT symptoms were: BG 14.7, PL 13.2, RO 12.5, SK 11.4 and SB 9.8 – out of a maximum of 40, with higher scores representing more severe symptoms. The impact of symptoms was most apparent for night awakenings (BG 39.5%, PL 28.7%, RO 36.0%, SK 34.0%, SB 27.2%) and tiredness during the day (BG 81.0%, PL 70.7%, RO 79.0%, SK 60.0%, SB 66.2%). Mean CAT scores ranged from 15 in SK and SB to almost 17 in PL, 19 in RO, and 19.2 in BG. The distribution of low burden (A/C) vs. high burden (B/D) symptom categories by GOLD 2017 report differed at country level: 27.2% vs. 72.8% in BG, 35.9% vs. 64.1% in PL, 27.6% vs. 72.4% in RO, 32.5% vs. 67.5% in SK and 48.4% vs. 51.6% in SB. The majority of patients received COPD maintenance treatment: 98.8% in PL and SB, 99% in RO and SK and 100% in BG. CONCLUSIONS: Despite regular treatment, symptoms place a high burden in stable COPD patients from CEE countries. Symptoms are variable and impact daily life of patients. CLINICAL IMPLICATIONS: Comprehensive assessment of respiratory symptoms can prove beneficial towards a more personalized treatment of patients with COPD. DISCLOSURES: Employee relationship with AstraZeneca Please note: $1001 - $5000 Added 03/10/2019 by Silviu Alecu, source=Web Response, value=Salary No relevant relationships by Adam Antczak, source=Web Response Employee relationship with AstraZeneca Please note: $1001 - $5000 Added 03/14/2019 by Yunqin Chen, source=Web Response, value=Salary No relevant relationships by Florin Mihaltan, source=Web Response No relevant relationships by Vesna Radulović, source=Web Response

Evidence-based review of data on the combination inhaler umeclidinium/vilanterol in patients with COPD.

The use of inhaled, fixed-dose, long-acting muscarinic antagonists (LAMA) combined with long-acting, beta2-adrenergic receptor agonists (LABA) has become a mainstay in the maintenance treatment of chronic obstructive pulmonary disease (COPD). One of the fixed-dose LAMA/LABA combinations is the dry powder inhaler (DPI) of umeclidinium bromide (UMEC) and vilanterol trifenatate (VI) (62.5 µg/25 µg) approved for once-a-day maintenance treatment of COPD. This paper reviews the use of fixed-dose combination LAMA/LABA agents focusing on the UMEC/VI DPI inhaler in the maintenance treatment of COPD. The fixed-dose combination LAMA/LABA inhaler offers a step beyond a single inhaled maintenance agent but is still a single device for the COPD patient having frequent COPD exacerbations and persistent symptoms not well controlled on one agent. Currently available clinical trials suggest that the once-a-day DPI of UMEC/VI is well-tolerated, safe and non-inferior or better than other currently available inhaled fixed-dose LAMA/LABA combinations for COPD.

Single Inhaler LABA/LAMA for COPD.

Chronic obstructive pulmonary disease (COPD) is a common disabling disease characterized by progressive airflow obstruction. Great efforts were spent in the development of drugs able to improve symptoms, quality of life, reduce exacerbations, hospitalizations and the frequency of death of patients with COPD. The cornerstones of treatment are bronchodilator drugs of two different classes: beta agonists and muscarinic antagonists. Currently the Global initiative for COPD suggests the use of long acting beta agonists (LABAs) and long acting muscarinic antagonists (LAMAs) in combination for the majority of COPD patients, thus great interest is associated with the developing of LAMA/LABA fixed combination in the maintenance treatment of stable COPD. Many LAMA/LABA fixed dose combinations have been licensed in different countries and the clinical use of these drugs stimulated the performance of many clinical trials. The purpose of this review is a complete criticism of pharmacological and clinical aspects related to the use of LAMA/LABA single inhalers for the maintenance treatment of stable COPD, with particular mention to the most debated topics and future prospects in the field.

Patient preference for a maintenance inhaler in chronic obstructive pulmonary disease: a comparison of Breezhaler and Respimat.

Good compliance in chronic obstructive pulmonary disease (COPD) is of 'paramount importance' in reducing the occurrence of acute exacerbations, hospitalisation and mortality and in improving quality of life. However, a number of studies have confirmed that long-term compliance is low and often associated with difficulties in handling maintenance inhalers. Therefore, the easier an inhaler is to use, the more likely the patient will comply with handling instructions and so, optimise control of the condition. A research study was undertaken comparing the maintenance inhalers BreezhalerTM (BH-available in combination with Ultibro, Seebri and Onbrez from Novartis) and RespimatTM (RM-available in combination with Spiriva, Spiolto and Striverdi from Boehringer Ingelheim). The research was conducted among 240 maintenance inhaler-naive participants who before handling the inhalers were asked to indicate how important they felt it was that an inhaler offered each of a list of 22 handling-related attributes. They then handled each inhaler on three separate occasions familiarising themselves with the correct handling procedure by consulting respective 'Instructions for use' and short training videos. Following the handling process, participants rated the individual inhaler against each of the 22 attributes and finally expressed their preference between the two on a number of key handling-related attributes and indicated which they preferred overall. A significant majority of participants preferred BH to RM overall. BH was rated statistically superior on 20 of the 22 handling-related attributes particularly those participants rated most highly including dosing confidence, 'easy to use' and 'easy to learn'. Significantly more participants were confident that BH would deliver a full dose of medication and was easier to learn and use. These attributes are crucial for achieving improved patient compliance. As a result, BH offers an opportunity for improved symptom control in the maintenance treatment of COPD.

PRS49 - COST-EFFECTIVENESS OF THE FIXED-DOSE COMBINATION TIOTROPIUM + OLODATEROL VERSUS TIOTROPIUM BASED ON THE DYNAGITO TRIAL RESULTS IN FRANCE

Combinations of long-acting bronchodilators are recommended to reduce the rate of chronic obstructive pulmonary disease (COPD) exacerbations. Evidence from a recent head-to-head trial, DYNAGITO, suggests that the fixed dose combination tiotropium+olodaterol (TIO+OLO) produces a reduction in the risk of exacerbating compared with tiotropium monotherapy (TIO). This study assessed the cost-effectiveness of TIO+OLO versus TIO in the French setting. A recently developed COPD patient-level simulation model was used to estimate the lifetime effects and costs for 15,000 patients receiving either TIO+OLO or TIO by applying the difference in annual exacerbation rate as observed in the DYNAGITO trial. The unit costs for treatment medication, COPD maintenance treatment, COPD exacerbations (moderate and severe) and pneumonias were obtained from relevant sources in France. The main outcomes were the annual exacerbation rate, quality-adjusted life-years (QALYs) and lifetime costs. Analyses were performed from a societal perspective. Patients receiving TIO+OLO benefitted from QALYs gain as compared to those treated with TIO: on average + 0.042 QALYs per patient over lifetime (PSA: 0.043 (95% UI: -0.015; 0.102)). The higher treatment medication costs for TIO+OLO versus TIO (+€1,640) were not completely compensated by the reduction in exacerbation costs (-€1,540), but the resulting difference in total costs between TIO + OLO versus TIO was small +€123 (PSA: €131 (95% UI: -€1021; €1026). The base case cost-effectiveness ratio (ICER) of TIO+OLO vs OLO was €2,900 per QALY. This finding was consistent across all sensitivity analyses conducted. On the basis of the results of the DYNAGITO trial, TIO+OLO is cost-effective versus TIO in COPD patients in France with a low cost per QALY.

Effect of long-acting β2-agonists olodaterol and formoterol on heart rate and blood pressure in chronic obstructive pulmonary disease patients

BackgroundCardiovascular comorbidities are common in chronic obstructive pulmonary disease (COPD), and elevated heart rate reflects increased cardiovascular risk over time, which is associated with unfavourable neurohumoral activation. Long-acting β2-agonists (LABAs) are established treatments in COPD, but potentially increase heart rate. We report a post hoc pooled analysis of the effect of olodaterol (5 or 10 μg) or formoterol (12 μg) on heart rate and blood pressure (BP) in Global Initiative for Chronic Obstructive Lung Disease Stage 2–4 COPD patients. MethodsFour randomised, double-blind, placebo-controlled, Phase III studies were analysed. Changes in heart rate and systolic/diastolic BP were measured before and after dosing with the study medication at each visit. ResultsAt each study visit, the increase in pre-dose heart rate was numerically lower with both LABAs compared with placebo. Systolic and diastolic BP were decreased with all treatments. Short-term (pre-dose to 40 min post-dose) effects of drug administration on heart rate were small and similar for all treatment arms (between −3 and +1 beats per minute). ConclusionHeart rate and BP were not adversely influenced in this study involving long-term administration of olodaterol or formoterol in patients with moderate-to-severe COPD. This supports the cardiovascular safety of LABAs in COPD maintenance treatment.

Long-Term Evaluation of the Effects of Aclidinium Bromide on Major Adverse Cardiovascular Events and COPD Exacerbations in Patients with Moderate to Very Severe COPD: Rationale and Design of the ASCENT COPD Study.

Introduction: Chronic obstructive pulmonary disease (COPD) is a heterogeneous illness characterized by persistent airflow obstruction and exacerbations. Patients typically experience a decline in lung function, increasingly impaired health-related quality of life, and high mortality. Poor lung function and exacerbations are associated with an increased risk of cardiovascular (CV) and cerebrovascular events, and approximately 30% of patients with COPD die from CV‑related disease. Treatment with inhaled long-acting bronchodilators, such as long-acting muscarinic antagonists (LAMAs), is recommended; however, some studies have suggested that LAMAs may increase the risk of CV events. As patients with CV and cerebrovascular conditions are often excluded from clinical trials, an evaluation of the safety of COPD treatments in an at-risk population is vital. Aclidinium bromide is a LAMA approved for the long-term maintenance treatment of COPD. Methods and Objectives: The Phase 4, multicenter, double-blind, randomized, placebo-controlled, parallel-group Aclidinium Bromide on Long-Term Cardiovascular Safety and COPD Exacerbations in PatieNTs with Moderate to Very Severe COPD (ASCENT COPD) study (NCT01966107) is being conducted at 500 sites in the United States and Canada. The primary objectives are to evaluate the long-term effects of twice-daily aclidinium bromide 400 µg on CV safety and exacerbations in patients with moderate to very severe COPD with a history of cerebrovascular, coronary, or peripheral artery disease, or the presence of ≥2 atherothrombotic risk factors. The primary safety and efficacy variables are time to first major adverse CV event (MACE) (on-study analysis) and rate of moderate to severe COPD exacerbations during the first year of treatment (on-treatment analysis), respectively. The study will be terminated after approximately 122 MACE have occurred.

Improvements in Health Status With Revefenacin, a Once-Daily Long-Acting Muscarinic Antagonist for Nebulization: Changes in St George’s Respiratory Questionnaire and COPD Assessment Test in Replicate 3-Month Studies

SESSION TITLE: New Perspectives in COPD Morbidity SESSION TYPE: Original Investigation Slide PRESENTED ON: Sunday, October 29, 2017 at 07:30 AM - 08:30 AM PURPOSE: Revefenacin, a novel once-daily, long-acting muscarinic antagonist (LAMA), is under development as a nebulized maintenance treatment of chronic obstructive pulmonary disease (COPD). We reported that revefenacin 88 and 175 μg significantly improved the forced expiratory volume in 1 second (trough, peak, and overall treatment effect; P≤0.001) in replicate 3-month studies. Adverse events were similar between the two doses and placebo. In this secondary analysis, we measured changes in health status using the St George’s Respiratory Questionnaire (SGRQ) and COPD Assessment Test (CAT). METHODS: In these replicate, 3-month, double-blind, parallel-group studies, 1256 participants with moderate to very severe COPD were randomized (1:1:1) to one of three treatment groups (placebo [n=429], revefenacin 88 μg [n=425], or 175 μg [n=402]). We administered the SGRQ (secondary endpoint) and CAT (exploratory endpoint) as patient-reported outcomes at baseline and on day 85, using both responder (defined as participants with a score decrease of ≥4) and change from baseline analyses. RESULTS: SGRQ total scores were similar between the two studies at baseline. In Study 0126, nominally significant, clinically relevant improvements in SGRQ were observed with revefenacin vs placebo in both responder (odds ratios [ORs] for revefenacin/placebo: revefenacin 88 µg, 2.06 [P=0.0203]; revefenacin 175 µg, 2.11 [P=0.0183]) and total score (least square [LS] mean placebo-adjusted changes from baseline: revefenacin 88 µg, -4.68 [P=0.0001]; revefenacin 175 µg, -4.16 [P=0.0009]) analyses. In Study 0127, however, only the change from baseline analysis at 175 µg reached statistical significance over placebo (due to a greater than expected placebo response), despite similar responder (ORs for revefenacin/placebo: revefenacin 88 µg, 1.31 [P=0.3719]; revefenacin 175 µg, 1.26 [P=0.4402]) and total score (LS mean placebo-adjusted changes from baseline: revefenacin 88 µg, -1.30 [P=0.2705]; revefenacin 175 µg, -2.58 [P=0.0209]) changes. The 175 µg dose demonstrated greater odds of showing improvement using 8-point and 12-point improvement responder definitions in both studies relative to the 88 µg dose. CAT results were generally consistent with SGRQ and will be presented in the poster. CONCLUSIONS: Replicate 3-month studies demonstrated improvements in the health status of COPD patients treated with revefenacin. Study 0126 demonstrated statistically significant improvements in both SGRQ and CAT. In Study 0127, a greater than expected placebo response precluded replication of Study 0126 results. An ongoing longer-term study may help further elucidate the effects of revefenacin on health status. CLINICAL IMPLICATIONS: Maintenance treatment with revefenacin may improve the health status of patients with COPD. Assuming a favorable regulatory review, revefenacin may become the first once-daily nebulized bronchodilator for the maintenance treatment of COPD. DISCLOSURE: James Donohue: Consultant fee, speaker bureau, advisory committee, etc.: JD has served as an ad hoc advisor and recieved honorarium on 3 occasions Srikanth Pendyala: Employee: SR is an employee of Theravance Biopharma US, Inc. Chris Barnes: Employee: CNB is an employee of Theravance Biopharma US, Inc. Edmund Moran: Employee: EJM is an employee of Theravance Biopharma US, Inc. Glenn Crater: Employee: GDC is an employee of Theravance Biopharma US, Inc. Revefenacin is currently being evaluated in phase 3 clinical trials

GOLD 2017 treatment pathways in 'real life': An analysis of the DACCORD observational study.

The 2017 update to the Global Initiative for Obstructive Lung Disease (GOLD) strategy document includes recommendations for treatment intensification or step-down in chronic obstructive pulmonary disease (COPD), although recognises that limited supporting information is available. DACCORD is an ongoing observational, non-interventional study, recruiting patients following COPD maintenance treatment change or initiation, a subset of whom were receiving a long-acting β2-agonist (LABA) plus a long-acting muscarinic antagonist (LAMA) fixed-dose combination (FDC) on entry. Since there were no requirements in terms of prior medication (and no washout before commencing LABA/LAMA FDC), this provides an opportunity to generate 'real world' data to test the GOLD 2017 recommendations. To reduce heterogeneity, the current analyses include patients receiving indacaterol/glycopyrronium at baseline, and who, prior to the study, were receiving no COPD maintenance medication ('none'), LABA or LAMA monotherapy ('mono'), LABA plus inhaled corticosteroid (ICS; 'LABA/ICS'), or triple therapy ('triple'). At the baseline visit, data collected included: demographic and disease characteristics; COPD Assessment Test (CAT); and exacerbations in the 6 months prior to entry. At 3, 6, 9 and 12 months data on exacerbations were collected, with CAT recorded at 3 and 12 months. A total of 2724 patients were included in the baseline analyses: 795, 954, 598 and 377 in the 'none', 'mono', 'LABA/ICS' and 'triple' subgroups, respectively. There were no clinically relevant differences in baseline demographics between the four groups. In terms of disease characteristics, the 'triple' group had the highest proportion of patients with a disease duration of more than 1 year since diagnosis and with severe/very severe airflow limitation, but a similar percentage of non-exacerbators compared to the 'none' group. Over the 1-year follow-up, the majority of patients in all four subgroups did not exacerbate (exacerbation rates 0.16, 0.19, 0.21, and 0.26 in the 'none', 'mono', 'LABA/ICS' and 'triple' groups, respectively). At 12 months, 61.4%, 65.0%, 71.0% and 52.4% of patients had a clinically relevant improvement in CAT score. Overall, the results support the GOLD recommendations in suggesting that a switch from a mono-bronchodilator or LABA plus ICS to LABA/LAMA FDC is a valid treatment option for patients with COPD. The results also validate the use of a LABA/LAMA FDC as initial maintenance treatment for COPD, and provide first 'real world' evidence to support the newly added 'step down' recommendation (from triple to LABA/LAMA FDC).

Can Assessment of Disease Burden Prior to Changes in Initial COPD Maintenance Treatment Provide Insight into Remaining Unmet Needs? A Retrospective Database Study in UK Primary Care

ABSTRACTThis retrospective cohort study aimed to assess treatment patterns over 24 months amongst patients with chronic obstructive pulmonary disease (COPD), initiating a new COPD maintenance treatment, and to understand clinical indicators of treatment change. Patients included in the study initiated a long-acting β2-agonist (LABA), a long-acting muscarinic antagonist (LAMA), or a combination of LABA and an inhaled corticosteroid (ICS/LABA) between January 1, 2009, and November 30, 2013, as recorded in the United Kingdom Clinical Practice Research Datalink (UK CPRD). Treatment modifications (switching or adding maintenance treatments) over 24 months were assessed, and patient characteristics, disease burden, medication and healthcare resource use during the 30 days before treatment modification were evaluated. The cohort comprised 17,258 patients [LABA (8%), LAMA (39%) and ICS/LABA (54%)] with similar age, body mass index and dyspnoea distribution. LABA users were more likely than LAMA users to add a maintenance therapy. Distinct patterns of treatment augmentations were noted, whereby LABA users typically received dual therapy before moving to triple therapy, while LAMA users moved to triple therapy by directly adding an ICS/LABA. Exacerbation events immediately prior to treatment change were not frequently recorded; however, the need for rescue short-acting medication and assessment of dyspnoea in the 30 days prior to the treatment change suggest that dyspnoea is a remaining unmet need driving therapy change.