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Journal of the American College of... Feb 2002
Topics: Coronary Artery Disease; Humans; Muscarinic Antagonists; Scopolamine
PubMed: 11849885
DOI: No ID Found -
The American Journal of Managed Care Feb 2024For patients with asthma who remain symptomatic on a medium-dose inhaled corticosteroid/long-acting β2 agonist, addition of a long-acting muscarinic antagonist as a...
OBJECTIVES
For patients with asthma who remain symptomatic on a medium-dose inhaled corticosteroid/long-acting β2 agonist, addition of a long-acting muscarinic antagonist as a supplementary controller is a recommended option. However, real-world data on the characteristics and treatment patterns of these patients are limited. This study described the demographics and clinical characteristics of new users of single- or multiple-inhaler triple therapy and treatment patterns preceding triple-therapy initiation.
STUDY DESIGN
This retrospective cohort study used medical and pharmacy claims data from the IQVIA PharMetrics Plus database.
METHODS
The study population comprised adults with asthma with or without chronic obstructive pulmonary disease (COPD) initiating triple therapy with single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI; 100/62.5/25 μg) or multiple-inhaler triple therapy (MITT) between September 18, 2017, and September 30, 2019. Demographics, clinical characteristics, and treatment patterns in the 12 months preceding triple-therapy initiation were described (baseline period).
RESULTS
A total of 12,395 patients were included. Among FF/UMEC/VI initiators with asthma (n = 1301), the mean age was 49.0 years and 59.3% were women. During the baseline period, 81.5% of patients used controller therapy, 94.7% used rescue medications, and 42.0% reported at least 1 asthma-related exacerbation; the annual mean exacerbation rate was 0.96. Similar trends were observed among patients with asthma initiating MITT and patients with comorbid asthma-COPD initiating FF/UMEC/VI or MITT.
CONCLUSION
In real-world practice, triple therapy is often utilized following other asthma controller medication use. High disease burden, as evidenced by substantial use of rescue medications and continued asthma-related exacerbations, suggests that patients may not have achieved adequate asthma control prior to triple-therapy initiation.
Topics: Adult; Humans; Female; Middle Aged; Male; Bronchodilator Agents; Retrospective Studies; Administration, Inhalation; Asthma; Pulmonary Disease, Chronic Obstructive; Fluticasone; Muscarinic Antagonists; Drug Combinations
PubMed: 38381542
DOI: 10.37765/ajmc.2024.89494 -
American Journal of Respiratory Cell... Nov 2022
Topics: Acetylcholine; Arrestin; Receptors, Muscarinic; Muscarinic Antagonists; Myocytes, Smooth Muscle
PubMed: 36049223
DOI: 10.1165/rcmb.2022-0335ED -
American Journal of Health-system... Jun 2021This article reviews the efficacy and safety of revefenacin, the first once-daily, long-acting muscarinic antagonist, when delivered via a standard jet nebulizer in... (Review)
Review
PURPOSE
This article reviews the efficacy and safety of revefenacin, the first once-daily, long-acting muscarinic antagonist, when delivered via a standard jet nebulizer in patients with chronic obstructive pulmonary disease (COPD).
SUMMARY
Revefenacin 175 µg is indicated for the maintenance treatment of patients with moderate to very severe COPD. Preclinical studies showed that revefenacin is a potent and selective antagonist with similar affinity for the different subtypes of muscarinic receptors (M1-M5). Furthermore, prevention of methacholine- and acetylcholine-induced bronchoconstrictive effects was dose dependent and lasted longer than 24 hours, demonstrating a long duration of action. In phase 2 and 3 trials, treatment with revefenacin was demonstrated to result in statistical improvements in pulmonary function (≥100 mL, P < 0.05) vs placebo, including among patients with markers of more severe disease and those who received concomitant long-acting β-agonists or long-acting β-agonists together with inhaled corticosteroids. Revefenacin was also demonstrated to have efficacy similar to that of tiotropium. The clinical trial findings indicated no significant difference between revefenacin and tiotropium with regard to rates of adverse events. Overall, revefenacin was well tolerated, with COPD worsening/exacerbation, dyspnea, headache, and cough among the most common adverse events noted in the clinical trials.
CONCLUSIONS
Revefenacin treatment delivered via nebulization led to improvements in lung function in patients with COPD. It was also generally well tolerated, with no major safety concerns. Revefenacin provides a viable treatment option for patients with COPD and may be a suitable alternative for those with conditions that may impair proper use of traditional handheld inhalers.
Topics: Administration, Inhalation; Benzamides; Bronchodilator Agents; Carbamates; Humans; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive
PubMed: 33821890
DOI: 10.1093/ajhp/zxab154 -
British Journal of Pharmacology May 2018The aim of this study was to develop potent and long-acting antagonists of muscarinic ACh receptors. The 4-hexyloxy and 4-butyloxy derivatives of...
BACKGROUND AND PURPOSE
The aim of this study was to develop potent and long-acting antagonists of muscarinic ACh receptors. The 4-hexyloxy and 4-butyloxy derivatives of 1-[2-(4-oxidobenzoyloxy)ethyl]-1,2,3,6-tetrahydropyridin-1-ium were synthesized and tested for biological activity. Antagonists with long-residence time at receptors are therapeutic targets for the treatment of several neurological and psychiatric human diseases. Their long-acting effects allow for reduced daily doses and adverse effects.
EXPERIMENTAL APPROACH
The binding and antagonism of functional responses to the agonist carbachol mediated by 4-hexyloxy compounds were investigated in CHO cells expressing individual subtypes of muscarinic receptors and compared with 4-butyloxy analogues.
KEY RESULTS
The 4-hexyloxy derivatives were found to bind muscarinic receptors with micromolar affinity and antagonized the functional response to carbachol with a potency ranging from 30 nM at M to 4 μM at M receptors. Under washing conditions to reverse antagonism, the half-life of their antagonistic action ranged from 1.7 h at M to 5 h at M receptors.
CONCLUSIONS AND IMPLICATIONS
The 4-hexyloxy derivatives were found to be potent long-acting M -preferring antagonists. In view of current literature, M -selective antagonists may have therapeutic potential for striatal cholinergic dystonia, delaying epileptic seizure after organophosphate intoxication or relieving depression. These compounds may also serve as a tool for research into cognitive deficits.
Topics: Animals; CHO Cells; Carbachol; Cells, Cultured; Cricetulus; Dose-Response Relationship, Drug; Molecular Structure; Muscarinic Antagonists; Pyridines; Receptors, Muscarinic; Structure-Activity Relationship
PubMed: 29498041
DOI: 10.1111/bph.14187 -
Respiratory Medicine Jul 2017Chronic obstructive pulmonary disease (COPD) and asthma are leading causes of morbidity and mortality. This narrative review provides an appraisal of the pharmacological... (Comparative Study)
Comparative Study Review
PURPOSE
Chronic obstructive pulmonary disease (COPD) and asthma are leading causes of morbidity and mortality. This narrative review provides an appraisal of the pharmacological and clinical characteristics of tiotropium in COPD and asthma, and examines how these compare with other long-acting bronchodilators. The evidence base is placed into context by relating it to factors affecting clinicians' choice of therapy.
MAIN FINDINGS
Desirable attributes of a long-acting muscarinic antagonist (LAMA) maintenance therapy include effective pharmacological bronchodilation, improved lung function, exacerbation efficacy, and positive effects on symptom control, exercise capacity and quality of life across a broad patient population. Tolerability and convenience of use are also important for patient well-being and treatment adherence. Tiotropium shows higher affinity for muscarinic receptors than ipratropium, and prolonged binding to the M receptor compared with other LAMAs. In COPD, tiotropium has demonstrated improved lung function and exacerbation prevention compared with placebo or long-acting β-agonists, similar exacerbation efficacy to other LAMAs, and enhanced symptom control and health status versus placebo. UniTinA-asthma showed the benefits of add-on tiotropium in patients with uncontrolled mild to moderate and severe asthma. Tiotropium is well tolerated, with an incidence of adverse events similar to placebo, except for known infrequent side effects of anticholinergics. Tiotropium HandiHaler and Respimat augment inhaler choice in COPD.
PRINCIPAL CONCLUSIONS
With over 10 years' prescribing history and 50 million patient-years of use, tiotropium has the benefit of a more extensive clinical evidence base than other long-acting bronchodilators, with demonstrated efficacy and safety in COPD and symptomatic asthma.
Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Asthma; Bronchodilator Agents; Cholinergic Antagonists; Disease Progression; Exercise Tolerance; Forced Expiratory Volume; Humans; Ipratropium; Muscarinic Antagonists; Nebulizers and Vaporizers; Patient Outcome Assessment; Pulmonary Disease, Chronic Obstructive; Quality of Life; Respiratory Function Tests; Tiotropium Bromide
PubMed: 28610667
DOI: 10.1016/j.rmed.2017.04.008 -
International Journal of Chronic... 2017Several fixed-dose combinations (FDCs) of long-acting bronchodilators (a long-acting muscarinic antagonist [LAMA] plus a long-acting β-agonist [LABA]) are available for... (Review)
Review
Several fixed-dose combinations (FDCs) of long-acting bronchodilators (a long-acting muscarinic antagonist [LAMA] plus a long-acting β-agonist [LABA]) are available for the treatment of COPD. Studies of these FDCs have demonstrated substantial improvements in lung function (forced expiratory volume in 1 second) in comparison with their respective constituent monocomponents. Improvements in patient-reported outcomes (PROs), such as symptoms and health status, as well as exacerbation rates, have been reported compared with a LABA or LAMA alone, but results are less consistent. The inconsistencies may in part be owing to differences in study design, methods used to assess study end points, and patient populations. Nevertheless, these observations tend to support an association between improvements in forced expiratory volume in 1 second and improvements in symptom-based outcomes. In order to assess the effects of FDCs on PROs and evaluate relationships between PROs and changes in lung function, we performed a systematic literature search of publications reporting randomized controlled trials of FDCs. Results of this literature search were independently assessed by two reviewers, with a third reviewer resolving any conflicting results. In total, 22 Phase III randomized controlled trials of FDC bronchodilators in COPD were identified, with an additional study including a post-literature search (ten for indacaterol-glycopyrronium once daily, eight for umeclidinium-vilanterol once daily, three for tiotropium-olodaterol once daily, and two for aclidinium-formoterol twice daily). Results from these studies demonstrated that the LAMA-LABA FDCs significantly improved lung function compared with their component monotherapies or other single-agent treatments. Furthermore, LABA-LAMA combinations also generally improved symptoms and health status versus monotherapies, although some discrepancies between lung function and PROs were observed. Overall, the safety profiles of the FDCs were similar to placebo. Further research is required to examine more closely any relationship between lung function and PROs in patients receiving LABA-LAMA combinations.
Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Clinical Trials as Topic; Disease Progression; Drug Combinations; Forced Expiratory Volume; Health Status; Humans; Least-Squares Analysis; Lung; Muscarinic Antagonists; Odds Ratio; Patient Reported Outcome Measures; Pulmonary Disease, Chronic Obstructive; Recovery of Function; Research Design; Treatment Outcome
PubMed: 28115839
DOI: 10.2147/COPD.S116719 -
Annals of Medicine Dec 2023The Global Initiative for Chronic Obstructive Lung Disease (GOLD) document suggests that patients with chronic obstructive pulmonary disease (COPD) should be divided... (Observational Study)
Observational Study
BACKGROUND
The Global Initiative for Chronic Obstructive Lung Disease (GOLD) document suggests that patients with chronic obstructive pulmonary disease (COPD) should be divided into a less symptomatic group. Moreover, single-inhaled drugs are recommended as initial inhalation therapy for them. However, many less symptomatic patients are provided double or triple-inhaled drugs as initial therapy in the real world. This study aimed to describe the inhalation prescriptions and compare the effects of different inhalation therapies on less symptomatic COPD patients.
PATIENTS AND METHODS
This was an observational study. Stable COPD patients were recruited and divided into a less symptomatic group including Groups A and C based on the GOLD 2019 document. We collected the data of inhalation therapies prescriptions. Then, the patients were classified into long-acting muscarinic antagonist (LAMA), long-acting β2-agonist (LABA) + inhaled corticosteroid (ICS), LABA + LAMA, and LABA + LAMA + ICS groups. All the patients were followed up for 1 year to collect exacerbation and mortality data.
RESULTS
We found that only 45.4% of patients in Group A and 43.6% of patients in Group C received reasonable inhalation therapy in reference to the GOLD document. In addition, the LAMA group had a higher forced expiratory volume in one second (FEV1), FEV1%pred, FEV1/forced vital capacity and peak expiratory flow compared with LABA + ICS, LABA + LAMA and LABA + LAMA + ICS groups. However, we did not find any significant differences of exacerbation, hospitalization and mortality during the follow-up among different inhalation therapies groups on less symptomatic COPD patients.
CONCLUSION
Over half of the less symptomatic patients received inhalation therapy that were inconsistent with the GOLD document recommendations in a Chinese population in the real world. In fact, the single inhaled drug of LAMA should be recommended and pulmonary function is not a good indicator for the choice of initial inhalation therapy in less symptomatic COPD patients.KEY MESSAGESOver half of the less symptomatic COPD patients received inhalation therapy that were inconsistent with the GOLD document recommendations in a Chinese population in the real world.The clinicians should offer a single inhaled drug of LAMA to less symptomatic COPD patients and pulmonary function is not a good indicator for the choice of initial inhalation therapy.
Topics: Humans; East Asian People; Pulmonary Disease, Chronic Obstructive; Muscarinic Antagonists; Lung; Administration, Inhalation; Drug Therapy, Combination; Adrenal Cortex Hormones; Respiratory Therapy; Bronchodilator Agents
PubMed: 36988161
DOI: 10.1080/07853890.2023.2192519 -
Scientific Reports May 2023Few studies have directly compared the incidence of pneumonia in patients on common chronic obstructive pulmonary disease (COPD) treatments such as long-acting...
Few studies have directly compared the incidence of pneumonia in patients on common chronic obstructive pulmonary disease (COPD) treatments such as long-acting muscarinic antagonists (LAMA) with those on inhaled corticosteroids and long-acting β-agonist (ICS/LABA). Moreover, risk factors for pneumonia in COPD are still unclear. We aimed to compare the incidence of pneumonia in COPD patients on LAMA and those on ICS/LABA and explored the risk factors associated with pneumonia. This nationwide cohort study used Korean National Health Insurance claim data from January 2002 to April 2016. Patients who received COPD medication, either LAMA or ICS/LABA, with the COPD diagnostic code, were selected. We enrolled patients with good compliance (medication possession ratio ≥ 80%). The primary outcome was pneumonia in COPD patients initiating LAMA or ICS/LABA. We investigated the risk factors associated with pneumonia, including the sub-types of ICS treatments. After propensity score matching, the incidence rate per 1000 person-years of pneumonia was 93.96 for LAMA (n = 1003) and 136.42 for ICS/LABA (n = 1003) patients (p < 0.001). The adjusted hazard ratio (HR) for pneumonia in patients on fluticasone/LABA was 1.496 (95% confidence interval [CI] 1.204-1.859) compared with LAMA (p < 0.001). In multivariable analysis, a history of pneumonia was a risk factor associated with pneumonia (HR 2.123; 95% CI 1.580-2.852; p < 0.001). The incidence of pneumonia was higher in COPD patients on ICS/LABA compared with those on LAMA. It is recommended that ICS use be avoided in COPD patients with high pneumonia risk.
Topics: Humans; Muscarinic Antagonists; Incidence; Cohort Studies; Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Adrenal Cortex Hormones; Drug Therapy, Combination; Pulmonary Disease, Chronic Obstructive; Pneumonia; Bronchodilator Agents
PubMed: 37210420
DOI: 10.1038/s41598-023-35223-3 -
International Journal of Chronic... 2023We analyzed the clinical characteristics and outcomes in non-frequent exacerbation patients with chronic obstructive pulmonary disease (COPD).
BACKGROUND
We analyzed the clinical characteristics and outcomes in non-frequent exacerbation patients with chronic obstructive pulmonary disease (COPD).
METHODS
In this retrospective cohort study, we enrolled patients with stable COPD from 12 hospitals. Non-frequent exacerbation was defined as less than two times of exacerbations in the past year. The non-frequent exacerbation patients were classified into less and more symptomatic groups based on the COPD Assessment Test (CAT) and modified Medical Research Council (mMRC). Finally, the non-frequent exacerbation patients with less and more symptomatic were classified into the long-acting muscarinic antagonist (LAMA), long-acting β2-agonist (LABA)+inhaled corticosteroids (ICS), LABA+LAMA, and LABA+LAMA+ICS groups. Minimum clinically important difference (MCID) was defined as a CAT score decrease of ≥ 2 during six months of follow-up. We recorded the number of exacerbations and mortality during one year of follow-up.
RESULTS
A total of 834 (67.5%) non-frequent exacerbation patients with COPD were included in this study. The non-frequent exacerbation patients had a higher education level and body mass index (BMI), and lower CAT and mMRC scores (<0.05). In addition, the non-frequent exacerbation patients had lower mortality and risk of future exacerbation, and were more likely to attain MCID (<0.05). Furthermore, the non-frequent exacerbation patients with more symptomatic COPD treated with LABA+LAMA or LABA+LAMA+ICS were more likely to attain MCID and had a lower risk of future exacerbation (<0.05). However, there were no significant differences among the different inhalation therapies in non-frequent exacerbation patients with less symptomatic COPD.
CONCLUSION
The non-frequent exacerbation patients with COPD had a higher education level and BMI, a lower symptom burden, and better outcomes. In addition, LABA+LAMA should be recommended to non-frequent exacerbation patients with more symptomatic COPD, while mono-LAMA should be recommended to non-frequent exacerbation patients with less symptomatic COPD as the initial inhalation therapy.
Topics: Humans; Asian People; Body Mass Index; East Asian People; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Retrospective Studies; Disease Progression
PubMed: 37599897
DOI: 10.2147/COPD.S417566