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1.
Eur Respir Rev ; 30(160)2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34415847

RESUMO

Most patients with COPD are recommended to initiate maintenance therapy with a single long-acting bronchodilator, such as a long-acting muscarinic antagonist or long-acting ß2-agonist. However, many patients receiving mono-bronchodilation continue to experience high symptom burden, suggesting that patients are frequently not receiving optimal treatment. Treatment goals for COPD are often broad and not individually tailored, making initial treatment response assessments difficult. A personalised approach to initial maintenance therapy, based upon an individual's symptom burden and exacerbation risk, may be more appropriate.An alternative approach would be to maximise bronchodilation early in the disease course of all patients with COPD. Evidence suggests that dual bronchodilation has greater and consistent efficacy for lung function and symptoms than mono-bronchodilation, whilst potentially reducing the risk of exacerbations and disease deterioration, with a similar safety profile to mono-bronchodilators. Improvements in lung function and symptoms between dual- and mono-bronchodilation have also been demonstrated in maintenance-naïve patients, who are most likely to resemble those at first presentation in a clinical setting. Despite promising results, there are several evidence gaps that need to be addressed to allow decision makers to evaluate the merits of a widespread earlier introduction of dual bronchodilation.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2 , Doença Pulmonar Obstrutiva Crônica , Administração por Inalação , Agonistas de Receptores Adrenérgicos beta 2/efeitos adversos , Broncodilatadores/efeitos adversos , Humanos , Antagonistas Muscarínicos/efeitos adversos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Resultado do Tratamento
2.
Expert Rev Respir Med ; 15(9): 1093-1106, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34137664

RESUMO

Introduction: Aclidinium/formoterol is a long-acting muscarinic antagonist (LAMA) and long-acting ß2-agonist (LABA) dual bronchodilator used as a maintenance treatment for patients with chronic obstructive pulmonary disease (COPD). The efficacy of aclidinium/formoterol has been demonstrated consistently in patients with moderate-to-severe COPD versus placebo and monocomponents, with a comparable safety profile.Areas covered: This review examines recent research findings that expand our understanding of the impact of aclidinium/formoterol on the burden of COPD. Reviewed outcomes include improvements in lung function, respiratory symptoms, health-related quality of life, exercise tolerance, exacerbation rates, and clinically important deteriorations. In addition, the reported cardiovascular safety of aclidinium and current LAMA/LABA treatment recommendations are discussed.Expert opinion: Aclidinium/formoterol reduces disease burden in patients with COPD, including those that are treatment-naïve, without a significant increase in safety risk compared with monotherapies. Furthermore, evidence supports an improvement in lung function over a 24-hour period with aclidinium/formoterol treatment versus monotherapy and placebo, which may offer an advantage over some once-daily LAMA/LABA combinations. In summary, the recent evidence discussed in this review adds weight to the use of LAMA/LABA combinations as an initial therapy for certain patients newly diagnosed with COPD.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2 , Broncodilatadores , Fumarato de Formoterol , Doença Pulmonar Obstrutiva Crônica , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Broncodilatadores/uso terapêutico , Combinação de Medicamentos , Fumarato de Formoterol/uso terapêutico , Humanos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Qualidade de Vida , Tropanos
4.
Pulm Ther ; 7(1): 47-57, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33284384

RESUMO

PURPOSE: The purpose of this review is to discuss the development of Wixela™ Inhub™, a generic equivalent of Advair Diskus®, a fixed-dose combination of fluticasone propionate/salmeterol powder for oral inhalation for patients with asthma whose symptoms are not controlled with inhaled corticosteroids alone and for those with chronic obstructive pulmonary disease (COPD) who are at a high risk for exacerbations. We provide an overview of the Inhub device and the bioequivalence studies that have been conducted to date. Briefly, the in vitro performance, improvements in forced expiratory volume in 1 s, and the fluticasone propionate/salmeterol dose strengths for Wixela Inhub and Advair Diskus were comparable. CONCLUSION: The bioequivalence demonstrated by the totality of clinical and in vitro data supports the use of Wixela Inhub and provides a treatment option for patients with asthma or COPD.

6.
BMC Pulm Med ; 20(1): 134, 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32393215

RESUMO

BACKGROUND: Revefenacin, a once-daily, long-acting muscarinic antagonist delivered via standard jet nebulizer, increased trough forced expiratory volume in 1 s (FEV1) in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) in prior phase 3 trials. We evaluated the efficacy of revefenacin in patients with markers of more severe COPD. METHODS: A post hoc subgroup analysis of two replicate, randomized, phase 3 trials was conducted over 12 weeks. Endpoints included least squares change from baseline in trough FEV1, St. George's Respiratory Questionnaire (SGRQ) responders, and transition dyspnea index (TDI) responders at Day 85. This analysis included patient subgroups at high risk for COPD exacerbations and compared patients who received revefenacin 175 µg and placebo: severe and very severe airflow limitation (percent predicted FEV1 30%-< 50% and < 30%), 2011 Global Initiative for Chronic Obstructive Lung Disease (GOLD) D, reversibility (≥ 12% and ≥ 200 mL increase in FEV1) to short-acting bronchodilators, concurrent use of long-acting ß agonists and/or inhaled corticosteroids, older age (> 65 and > 75 years), and comorbidity risk factors. RESULTS: Revefenacin demonstrated significant improvements in FEV1 versus placebo at Day 85 among the intention-to-treat (ITT) population and all subgroups. Additionally, there was a greater number of SGRQ and TDI responders in the ITT population and the majority of subgroups analyzed among patients who received revefenacin versus placebo. For the SGRQ responders, the odds of response (odds ratio > 2.0) were significantly greater in the revefenacin arm versus the placebo arm among the severe airflow obstruction, very severe airflow obstruction and 2011 GOLD D subgroups. For the TDI responders, the odds of response (odds ratio > 2.0) were significantly greater among the severe airflow obstruction subgroup and patients aged > 75 years. CONCLUSIONS: Revefenacin showed significantly greater improvements in FEV1 versus placebo in the ITT population and all subgroups. Furthermore, there were a greater number of SGRQ and TDI responders in the ITT population, and in the majority of patient subgroups among patients who received revefenacin versus placebo. Based on the data presented, revefenacin could be a therapeutic option among patients with markers of more severe COPD. TRIAL REGISTRATION: Clinical trials registered with www.clinicaltrials.gov (Studies 0126 [NCT02459080; prospectively registered 22 May 2015] and 0127 [NCT02512510; prospectively registered 28 July 2015]).


Assuntos
Benzamidas/administração & dosagem , Broncodilatadores/administração & dosagem , Carbamatos/administração & dosagem , Antagonistas Muscarínicos/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Administração por Inalação , Idoso , Idoso de 80 Anos ou mais , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Volume Expiratório Forçado , Humanos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Índice de Gravidade de Doença , Fatores de Tempo
7.
Artigo em Inglês | MEDLINE | ID: mdl-32341641

RESUMO

Purpose: Rescue medication use is common in chronic obstructive pulmonary disease (COPD) patients and tends to increase with symptoms and disease severity. An analysis of baseline rescue medication use was conducted to inform on patient phenotypes and subsequent effects on lung function, symptoms, and safety following 12 weeks of nebulized glycopyrrolate (GLY) 25 µg twice daily or placebo in patients with moderate-to-very-severe COPD. Patients and Methods: Pooled data from the 12-week, placebo-controlled GOLDEN 3 and 4 studies (n=781) were used to assign patients into quarters based on baseline rescue medication use (ie, average puffs-per-day) during the run-in period. Placebo-adjusted trough forced expiratory volume in 1 second (FEV1), St. George's Respiratory Questionnaire (SGRQ) total score and EXAcerbations of COPD Tool-Respiratory Symptoms (EXACT-RS) total score data were reported; safety was evaluated by reviewing the incidence of adverse events (AEs) and serious AEs (SAEs). Results: Baseline rescue medication use was a proxy for disease severity, evidenced by decreased lung function, increased health status scores, symptom scores and use of background long-acting ß2-agonists and inhaled corticosteroids across quarters and treatment groups. Treatment with GLY led to greater improvements from baseline in trough FEV1, SGRQ and EXACT-RS scores compared with placebo in all rescue medication use quarters. Additionally, the SGRQ and EXACT-RS exhibited greater improvement with increased baseline rescue medication use with GLY treatment. In the Q4 patients, SGRQ (≥4-unit reduction) or EXACT-RS (≥2-unit reduction) responders were significantly greater with GLY compared with placebo. AE and SAE incidences were similar across quartiles. Conclusion: These results suggest that baseline rescue medication use assessments may be useful in the management of COPD. Treatment with nebulized GLY improved lung function and symptom scores, regardless of baseline rescue medication use. These results support the use of nebulized GLY for the treatment of COPD, independent of baseline rescue medication use.


Assuntos
Glicopirrolato , Doença Pulmonar Obstrutiva Crônica , Administração por Inalação , Broncodilatadores/uso terapêutico , Método Duplo-Cego , Volume Expiratório Forçado , Glicopirrolato/uso terapêutico , Humanos , Antagonistas Muscarínicos/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Resultado do Tratamento
8.
Ther Adv Respir Dis ; 14: 1753466620905278, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32106777

RESUMO

BACKGROUND: Combinations of a long-acting muscarinic receptor antagonist (LAMA), long-acting ß-agonist (LABA), and inhaled corticosteroid (ICS) are used for patients with persistent chronic obstructive pulmonary disease (COPD) exacerbations on bronchodilator monotherapy. In this prespecified subgroup analysis, we assessed the efficacy and safety of the LAMA revefenacin in patients with COPD taking concomitant LABA, including ICS/LABA (LABA subgroup). METHODS: Efficacy data were obtained from two 12-week, replicate, placebo-controlled trials and safety data were pooled from the 12-week and a 52-week tiotropium-controlled trial. Patients received revefenacin 175 µg or placebo in the 12-week or tiotropium 18 µg in the 52-week studies. The efficacy endpoint was least squares (LS) mean change from baseline in trough forced expiratory volume in 1 second (FEV1). Clinical health outcomes were assessed using the St. George's Respiratory Questionnaire (SGRQ). RESULTS: Revefenacin produced similar improvements from baseline in trough FEV1 in the non-LABA and LABA subgroups [placebo-adjusted LS mean change (95% confidence interval) in day 85 trough FEV1, 150.9 (110.3-191.6) ml and 139.2 (82.9-195.5) ml; p < 0.0001 versus placebo]. Similar improvements were observed in SGRQ scores in the non-LABA and LABA subgroups [-3.3 (-5.4 to -1.2) and -3.4 (-6.3 to -0.6)]. Improvements in lung function and health outcomes were observed regardless of airflow obstruction severity. Revefenacin was well tolerated with more adverse events reported in the LABA than the non-LABA subgroup. CONCLUSIONS: Once daily revefenacin for nebulization can be an effective and well-tolerated treatment for patients who require concomitant use of LABA with or without ICS. CLINICALTRIALS.GOV IDENTIFIERS: NCT02512510, NCT02459080, NCT02518139 The reviews of this paper are available via the supplemental material section.


Assuntos
Corticosteroides/administração & dosagem , Agonistas Adrenérgicos beta/administração & dosagem , Benzamidas/administração & dosagem , Broncodilatadores/administração & dosagem , Carbamatos/administração & dosagem , Pulmão/efeitos dos fármacos , Antagonistas Muscarínicos/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Administração por Inalação , Corticosteroides/efeitos adversos , Agonistas Adrenérgicos beta/efeitos adversos , Idoso , Benzamidas/efeitos adversos , Broncodilatadores/efeitos adversos , Carbamatos/efeitos adversos , Ensaios Clínicos Fase III como Assunto , Esquema de Medicação , Quimioterapia Combinada , Feminino , Volume Expiratório Forçado , Humanos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Antagonistas Muscarínicos/efeitos adversos , Nebulizadores e Vaporizadores , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Recuperação de Função Fisiológica , Fatores de Tempo , Resultado do Tratamento
9.
Int J Chron Obstruct Pulmon Dis ; 14: 2835-2848, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31827323

RESUMO

Background: Ideally, treatment recommendations for maintenance therapy-naïve patients with COPD should be based on studies conducted specifically in this population. We have reviewed evidence from previous studies of pharmacological treatments in maintenance therapy-naïve patients with COPD and performed a new post-hoc analysis of dual bronchodilator treatment in this population, aiming to assess the effectiveness of these interventions. Materials and methods: A literature review identified clinical trials that included analyses of patients with COPD who were maintenance therapy-naïve with long-acting ß2-agonists (LABA) or long-acting muscarinic antagonists (LAMA). Additionally, a post-hoc subgroup analysis was conducted for maintenance therapy-naïve patients with COPD in two large phase III, randomized, double-blind, 24-week trials investigating the efficacy of aclidinium bromide/formoterol fumarate (AB/FF) fixed-dose combination versus monotherapy or placebo (ACLIFORM [NCT01462942] and AUGMENT [NCT01437397]). Results: Treatment-naïve patients with COPD often represent a population of patients at the earliest stage at which most patients seek treatment. Of nine relevant studies identified, all reported positive findings for efficacy of LABA, LAMA, or LABA/LAMA treatment in maintenance therapy-naïve populations. Improvements were observed in lung function, symptoms, and health status versus monotherapy or placebo. Post-hoc analysis of ACLIFORM and AUGMENT demonstrated that AB/FF was effective in improving lung function in patients who had received no prior maintenance therapy. AB/FF showed improvements in 1 hr post-dose FEV1, trough FEV1, and patient-reported outcomes versus placebo and monotherapies. Combined with reviews of previous studies in maintenance therapy-naïve patients, these findings suggest that earlier intervention with a dual bronchodilator maintenance therapy, such as AB/FF, may provide significantly greater benefits than LAMA or LABA mono-bronchodilator therapy as a first maintenance treatment for COPD. Conclusion: These data show that therapeutic intervention is effective in treatment-naïve patients. Intervention with dual bronchodilator therapy as a first maintenance treatment for COPD may provide greater benefits than LAMA or LABA monotherapy.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Broncodilatadores/administração & dosagem , Pulmão/efeitos dos fármacos , Antagonistas Muscarínicos/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Administração por Inalação , Agonistas de Receptores Adrenérgicos beta 2/efeitos adversos , Broncodilatadores/efeitos adversos , Ensaios Clínicos Fase III como Assunto , Progressão da Doença , Combinação de Medicamentos , Volume Expiratório Forçado , Humanos , Pulmão/fisiopatologia , Antagonistas Muscarínicos/efeitos adversos , Nebulizadores e Vaporizadores , Estudos Observacionais como Assunto , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Recuperação de Função Fisiológica , Fatores de Tempo , Resultado do Tratamento
10.
Respir Res ; 20(1): 241, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31666076

RESUMO

BACKGROUND: Revefenacin is a long-acting muscarinic antagonist that was recently approved for the nebulized treatment of chronic obstructive pulmonary disease (COPD). Although shorter duration studies have documented the efficacy of revefenacin in COPD, longer-term efficacy has not been described. In a recent 52-week safety trial, revefenacin was well tolerated and had a favorable benefit-risk profile. Here we report exploratory efficacy and health outcomes in patients receiving revefenacin 175 µg or 88 µg daily during the 52-week trial. METHODS: In this randomized, parallel-group, 52-week trial (NCT02518139), 1055 participants with moderate to very severe COPD received revefenacin 175 µg or 88 µg in a double-blind manner, or open-label active control tiotropium. RESULTS: Over the 52-week treatment period, both doses of revefenacin, as well as tiotropium, elicited significant (all p < 0.0003) improvements from baseline in trough forced expiratory volume in 1 s (FEV1). The trough FEV1 profile (least squares mean change from baseline) for revefenacin 175 µg ranged from 52.3-124.3 mL and the trough FEV1 profile for tiotropium ranged from 79.7-112.8 mL. In subgroup comparisons, the effect of revefenacin on trough FEV1 was comparable in patients taking concomitant long-acting ß-agonists, with or without inhaled corticosteroids, with patients who were not taking these medications. There were statistically significant (p < 0.05) improvements in all measured health status outcomes (evaluated using St. George's Respiratory Questionnaire, COPD Assessment Test, Clinical COPD Questionnaire and Baseline and Transition Dyspnea Index) from 3 months onward, in all treatment arms. CONCLUSIONS: Significant sustained improvements from baseline in trough FEV1 and respiratory health outcomes were demonstrated for 175-µg revefenacin over 52 weeks, further supporting its use as a once-daily bronchodilator for the nebulized treatment of patients with COPD. TRIAL REGISTRATION: NCT02518139 ; Registered 5 August 2015.


Assuntos
Benzamidas/administração & dosagem , Broncodilatadores/administração & dosagem , Carbamatos/administração & dosagem , Antagonistas Muscarínicos/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Índice de Gravidade de Doença , Idoso , Método Duplo-Cego , Esquema de Medicação , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Volume Expiratório Forçado/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Resultado do Tratamento
11.
Chronic Obstr Pulm Dis ; 6(4)2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31647856

RESUMO

UNLABELLED: Chronic obstructive pulmonary disease is the third leading cause of death and disease burden worldwide. It includes a spectrum of diseases including chronic bronchitis which is characterized by overproduction, hypersecretion and decreased elimination of mucus. Chronic bronchitis has numerous clinical consequences, including predisposition to lower respiratory tract infections, accelerated decline in lung function, increased exacerbation rate and decreased health-related quality of life. UNLABELLED: Although the inflammatory mechanisms responsible for mucus cell metaplasia in chronic obstructive pulmonary disease and stable chronic bronchitis are poorly understood, the main goals of therapy are to decrease mucus hypersecretion by controlling inflammation and to increase mucus clearance. Non-pharmacological measures include smoking cessation and chest physiotherapy. Pharmacological interventions include expectorants and mucolytics together with long-acting beta2-adrenergic receptor agonists, anticholinergics, glucocorticoids, phosphodiesterase-4 inhibitors, antioxidants, and antibiotics. UNLABELLED: Guaifenesin is an expectorant that is thought to increase hydration and decrease viscosity of mucus leading to improved clearance of accumulated secretions from the upper and lower airway. Although guaifenesin has a Food and Drug Administration Over-the-Counter (OFC) Monograph indication to "help loosen phlegm (mucus) and thin bronchial secretions in patients with stable chronic bronchitis," there is limited published evidence of either mechanism of action or clinical efficacy in this disease state. Here we review the pathophysiology and consequences of chronic mucus hypersecretion and examine the evidence for the use of guaifenesin in patients with stable chronic bronchitis.

12.
Respir Res ; 20(1): 141, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31286970

RESUMO

There is increasing focus on understanding the nature of chronic obstructive pulmonary disease (COPD) during the earlier stages. Mild COPD (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 1 or the now-withdrawn GOLD stage 0) represents an early stage of COPD that may progress to more severe disease. This review summarises the disease burden of patients with mild COPD and discusses the evidence for treatment intervention in this subgroup.Overall, patients with mild COPD suffer a substantial disease burden that includes persistent or potentially debilitating symptoms, increased risk of exacerbations, increased healthcare utilisation, reduced exercise tolerance and physical activity, and a higher rate of lung function decline versus controls. However, the evidence for treatment efficacy in these patients is limited due to their frequent exclusion from clinical trials. Careful assessment of disease burden and the rate of disease progression in individual patients, rather than a reliance on spirometry data, may identify patients who could benefit from earlier treatment intervention.


Assuntos
Tolerância ao Exercício/efeitos dos fármacos , Volume Expiratório Forçado/efeitos dos fármacos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Corticosteroides/farmacologia , Corticosteroides/uso terapêutico , Agonistas de Receptores Adrenérgicos beta 2/farmacologia , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Tolerância ao Exercício/fisiologia , Volume Expiratório Forçado/fisiologia , Humanos , Antagonistas Muscarínicos/farmacologia , Antagonistas Muscarínicos/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Resultado do Tratamento
13.
Pulm Pharmacol Ther ; 57: 101808, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31152911

RESUMO

The cardiovascular safety of revefenacin, an anticholinergic indicated for the maintenance treatment of patients with chronic obstructive lung disease (COPD), was evaluated in phase 3 trials in patients with moderate to very severe COPD. No clinically meaningful changes in 12-lead electrocardiogram recordings were observed with up to 52 weeks of once-daily revefenacin 88 or 175 µg. In a pooled analysis of Studies 0126 and 0127, the incidence of prolonged QT interval corrected for heart rate using the Fridericia correction formula (QTcF; >450 msec) for revefenacin 88 µg (n = 23, 5.6%) and revefenacin 175 µg (n = 23, 5.9%) was similar to that for placebo (n = 22, 5.3%). In Study 0128, the incidence of prolonged QTcF was similar in the revefenacin 175 µg (n = 25, 7.7%) and tiotropium (n = 26, 7.3%) groups and lower in the revefenacin 88 µg (n = 15, 4.2%) group. There were four major adverse cardiac events (MACEs) in Study 0126 (one, two, and one in the placebo, revefenacin 88 µg, and revefenacin 175 µg groups, respectively), no MACEs in Study 0127 and 26 MACEs in Study 0128 (9, 10 and 7 in the revefenacin 88 µg, revefenacin 175 µg and tiotropium groups, respectively). In Study 0128, only one MACE was considered possibly/probably related to revefenacin (atrial fibrillation in the revefenacin 175 µg group). Thus, revefenacin may provide beneficial nebulized therapy for patients with COPD without further elevating their risk of cardiovascular events.


Assuntos
Benzamidas/administração & dosagem , Benzamidas/uso terapêutico , Broncodilatadores/administração & dosagem , Broncodilatadores/uso terapêutico , Carbamatos/administração & dosagem , Carbamatos/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Administração por Inalação , Adulto , Idoso , Idoso de 80 Anos ou mais , Benzamidas/efeitos adversos , Broncodilatadores/efeitos adversos , Carbamatos/efeitos adversos , Método Duplo-Cego , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antagonistas Muscarínicos/administração & dosagem , Nebulizadores e Vaporizadores , Medição de Risco , Brometo de Tiotrópio/administração & dosagem
14.
Respir Med ; 153: 38-43, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31150963

RESUMO

BACKGROUND: Prior replicate 12-week phase 3 trials demonstrated that once-daily doses of revefenacin inhalation solution at 88 µg and 175 µg produced significant bronchodilation over 24 h post dose in patients with moderate to very severe chronic obstructive pulmonary disease (COPD). The objective was to characterize the safety profile of revefenacin 88 µg and 175 µg over 52 weeks of treatment. METHODS: In this randomized, parallel-group, 52-week trial (NCT02518139), 1055 participants with moderate to very severe COPD received revefenacin 88 µg or 175 µg in a double-blind manner, or open-label active control tiotropium. RESULTS: Treatment-emergent adverse events (AEs) were comparable across all treatment groups (n [%] patients; revefenacin 88 µg, 272 [74.7%]; 175 µg, 242 [72.2%]; tiotropium, 275 [77.2%]). Numerically fewer COPD exacerbations (n [%] patients) were observed with revefenacin 175 µg (73 [21.8%]) than with 88 µg (107 [29.4%]) or tiotropium (100 [28.1%]). Serious AEs were comparable with revefenacin 88 µg (58 [15.9%] and tiotropium (58 [16.3%]), but were lower with revefenacin 175 µg (43 [12.8%]), and mortality was low. In patients using revefenacin 88 µg or tiotropium with a concurrent long-acting ß-agonist (LABA) product, the incidence of AEs was slightly higher than without concurrent LABA. LABA did not affect the incidence of AEs for patients who received revefenacin 175 µg. CONCLUSIONS: Revefenacin was generally well tolerated over 52 weeks of treatment, and had a safety profile that supports its use as a long-term once-daily bronchodilator for the nebulized treatment of COPD.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Benzamidas/uso terapêutico , Carbamatos/uso terapêutico , Antagonistas Muscarínicos/uso terapêutico , Nebulizadores e Vaporizadores/normas , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Administração por Inalação , Idoso , Benzamidas/administração & dosagem , Benzamidas/efeitos adversos , Broncodilatadores/uso terapêutico , Carbamatos/administração & dosagem , Carbamatos/efeitos adversos , Estudos de Casos e Controles , Antagonistas Colinérgicos/uso terapêutico , Progressão da Doença , Quimioterapia Combinada , Tolerância a Medicamentos , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Antagonistas Muscarínicos/administração & dosagem , Antagonistas Muscarínicos/efeitos adversos , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Segurança , Índice de Gravidade de Doença , Brometo de Tiotrópio/uso terapêutico , Capacidade Vital/efeitos dos fármacos
15.
Ther Adv Respir Dis ; 13: 1753466619850725, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31096854

RESUMO

Aclidinium bromide/formoterol fumarate (AB/FF) 400/12 µg is a twice-daily long-acting muscarinic receptor antagonist and long-acting ß2 agonist (LAMA/LABA) dual-bronchodilator maintenance therapy used to relieve symptoms and reduce future risk of exacerbations in adults with chronic obstructive pulmonary disease (COPD). To date, there have been several clinical studies and post hoc analyses of AB/FF, assessing treatment outcomes in patients with moderate-to-severe COPD. These studies have looked at a range of outcomes, including lung function parameters, patient-reported symptom scores, quality-of-life measures assessing impaired health and perceived well-being, and the frequency, duration, and severity of exacerbations. In light of the major 2017 revision to the Global initiative for chronic Obstructive Lung Disease (GOLD) recommendations, and the subsequent updates, we present an update on the latest evidence supporting the efficacy and safety of AB/FF. This review discusses the clinical relevance of the improvements in lung function, symptoms, quality of life, and exacerbations in patients with COPD reported in the phase III and IV trials of AB/FF. Given the current concerns over unnecessary inhaled corticosteroid (ICS) use in COPD, we also touch briefly on the use of blood eosinophils as a biomarker for identifying those patients with COPD already using LAMA/LABA therapy for whom the addition of ICS might be of benefit.


Assuntos
Fumarato de Formoterol/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Tropanos/administração & dosagem , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Agonistas de Receptores Adrenérgicos beta 2/farmacologia , Adulto , Broncodilatadores/administração & dosagem , Broncodilatadores/farmacologia , Combinação de Medicamentos , Fumarato de Formoterol/farmacologia , Humanos , Antagonistas Muscarínicos/administração & dosagem , Antagonistas Muscarínicos/farmacologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Qualidade de Vida , Índice de Gravidade de Doença , Tropanos/farmacologia
16.
Artigo em Inglês | MEDLINE | ID: mdl-30880938

RESUMO

Background: Aclidinium/formoterol 400/12 µg is a twice-daily maintenance bronchodilator for COPD. This post hoc study evaluated aclidinium/formoterol vs aclidinium 400 µg, formoterol 12 µg, or placebo in patient subgroups. Patients and methods: Data were pooled from two 24-week Phase III clinical trials (ACLIFORM and AUGMENT). Patients (N=3,394) were analyzed by baseline airflow obstruction severity (moderate/severe), age (<65/≥65 years), sex, and exacerbation history (0/≥1 exacerbation in the previous 12 months). Changes from baseline vs placebo and mono-therapies were evaluated: morning pre-dose (trough) and morning 1-hour post-dose FEV1, Transition Dyspnea Index (TDI), and moderate/severe exacerbation rates (healthcare resource utilization [HCRU] and EXAcerbations of Chronic pulmonary disease Tool [EXACT] criteria). Results: Aclidinium/formoterol improved the post-dose FEV1 vs placebo and monotherapy in all subgroups (all P<0.01) and trough FEV1 vs placebo (P<0.001) and formoterol (P<0.05) across all subgroups. Improvements in trough FEV1 were observed vs aclidinium in patients with severe airflow obstruction, patients aged <65 years, males, and patients with exacerbation history (P<0.05). Improvements in TDI were observed vs placebo in all subgroups (all P<0.001), monotherapies for patients with moderate (formoterol P<0.05) or severe airflow obstruction (aclidinium P<0.05), patients aged <65 years (aclidinium P<0.01, formoterol P<0.05), males (formoterol P<0.05), and patients with no exacerbation history (formoterol P<0.05). HCRU exacerbation rates were lower for aclidinium/formoterol vs placebo in patients with no exacerbation history (P<0.01). EXACT exacerbation rates were lower for aclidinium/formoterol in patients with moderate airflow obstruction vs placebo and aclidinium, patients aged <65 years vs placebo and ≥65 years vs formoterol, males vs placebo, and patients with no exacerbation history vs placebo (all P<0.05). Conclusion: Aclidinium/formoterol significantly improved post-dose FEV1, trough FEV1, and TDI vs placebo across all subgroups and vs monotherapy in many subgroups. These findings further support the benefits of aclidinium/formoterol for all patients with COPD.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Broncodilatadores/administração & dosagem , Fumarato de Formoterol/administração & dosagem , Pulmão/efeitos dos fármacos , Antagonistas Muscarínicos/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Tropanos/administração & dosagem , Administração por Inalação , Agonistas de Receptores Adrenérgicos beta 2/efeitos adversos , Fatores Etários , Idoso , Broncodilatadores/efeitos adversos , Ensaios Clínicos Fase III como Assunto , Progressão da Doença , Combinação de Medicamentos , Feminino , Volume Expiratório Forçado , Fumarato de Formoterol/efeitos adversos , Humanos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Antagonistas Muscarínicos/efeitos adversos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Recuperação de Função Fisiológica , Índice de Gravidade de Doença , Fatores Sexuais , Fatores de Tempo , Resultado do Tratamento , Tropanos/efeitos adversos
17.
Artigo em Inglês | MEDLINE | ID: mdl-30880948

RESUMO

Purpose: Adequate peak inspiratory flow rate (PIFR) is required for drug dispersion with dry powder inhalers (DPIs). Prevalence of PIFR discordance (suboptimal PIFR with prescribed inhalers) and factors influencing device-specific PIFR are unclear in COPD. The objective of this study was to determine the prevalence of PIFR discordance and associated clinical factors in a stable COPD population. Patients and methods: An observational, single-center, cohort study was conducted including 66 outpatients with COPD. PIFR was measured using the In-Check™ Dial with applied resistance of prescribed inhalers. Participants were defined as discordant if measured PIFR was <30 L/min and <60 L/min for high and low-medium resistance devices, respectively, using an inspiratory effort the participant normally used with their prescribed DPI. Results: The median age of the COPD participants was 69.4 years, 92% were white and 47% were female. A total of 48% were using low-medium resistance DPIs (Diskus®/Ellipta®) and 76% used high-resistance DPI (Handihaler®). A total of 40% of COPD participants were discordant to prescribed inhalers. Female gender was the only factor consistently associated with lower PIFR. Shorter height was associated with reduced PIFR for low-medium resistance (r=0.44; P=0.01), but not high resistance (r=0.20; P=0.16). There was no correlation between PIFR by In-Check™ dial and PIFR measured by standard spirometer. Conclusion: PIFR is reduced in stable COPD patients, with female gender being the only factor consistently associated with reduced PIFR. Discordance with prescribed inhalers was seen in 40% of COPD patients, suggesting that many COPD patients do not generate adequate inspiratory force to overcome prescribed DPIs resistance in the course of normal use.


Assuntos
Inalação , Pulmão/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Administração por Inalação , Idoso , Idoso de 80 Anos ou mais , Resistência das Vias Respiratórias , Broncodilatadores/administração & dosagem , Inaladores de Pó Seco , Feminino , Volume Expiratório Forçado , Humanos , Pulmão/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , North Carolina/epidemiologia , Prevalência , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Fatores de Risco , Fatores Sexuais , Espirometria , Capacidade Vital
18.
Healthcare (Basel) ; 7(1)2019 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-30669305

RESUMO

Rationale/Objective: The Behavioral Risk Factor Surveillance System (BRFSS) health survey has been used to describe the epidemiology of chronic obstructive pulmonary disease (COPD) in the US. Through addressing respiratory symptoms and tobacco use, it could also be used to characterize COPD risk. METHODS: Four US states added questions to the 2015 BRFSS regarding productive cough, shortness of breath, dyspnea on exertion, and tobacco duration. We determined COPD risk categories: provider-diagnosed COPD as self-report, high-risk for COPD as ≥10 years tobacco smoking and at least one significant respiratory symptom, and low risk was neither diagnosed COPD nor high risk. Disease burden was defined by respiratory symptoms and health impairments. Data were analyzed using multiple logistic regression models with age as a covariate. RESULTS: Among 35,722 adults ≥18 years, the overall prevalence of COPD and high-risk for COPD were 6.6% and 5.1%. Differences among COPD risk groups were evident based on gender, race, age, geography, tobacco use, health impairments, and respiratory symptoms. Risk for disease was seen early where 3.75% of 25⁻34 years-old met high-risk criteria. Longer tobacco duration was associated with an increased prevalence of COPD, particularly >20 years. Seventy-nine percent of persons ≥45 years-old with frequent shortness of breath (SOB) reported having or being at risk of COPD, reflecting disease burden. CONCLUSION: These data, representing nearly 18% of US adults, indicates those at high risk for COPD share many, but not all of the characteristics of persons diagnosed with the disease and demonstrates the value of the BRFSS as a tool to define lung health at a population level.

19.
Pulm Ther ; 5(1): 23-41, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32026426

RESUMO

Inhaled fixed-dose combinations (FDCs) of a long-acting ß-agonist (LABA) and a long-acting muscarinic antagonist (LAMA) have become the cornerstone for the maintenance treatment of symptomatic COPD patients. In this regard, global COPD treatment guidelines have recognized the importance of inhaler devices as integral contributors to the effectiveness of LABA/LAMA FDCs and recommend regular assessment of inhaler device use by the patients in order to improve long-term clinical outcomes. Optimal disease control is also highly dependent upon patient preferences and adherence to inhaler devices. This review objectively examines and compares the major inhaler devices used to deliver different LABA/LAMA FDCs, discusses the inhaler device characteristics that determine drug deposition in the airways, real-life preference for inhaler devices, and handling of inhaler devices that impact the results of the long-term management of COPD. The introduction of new LABA/LAMA FDCs, new inhaler devices, and more clinical studies have created confusion among physicians in choosing the optimal inhaled therapy for COPD patients; in this context, this review attempts to provide an evidence-based framework for informed decision-making with a particular focus on the inhaler devices.Funding. The preparation of this manuscript was funded by Novartis Pharma AG.

20.
Int J Chron Obstruct Pulmon Dis ; 14: 2947-2958, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31908443

RESUMO

Bronchodilation with muscarinic antagonists, ß2-agonists, and inhaled corticosteroids remains the foundation of pharmaceutical treatment for patients with stable COPD. These drugs are delivered from a variety of devices, including dry powder inhalers, pressurized metered-dose inhalers, soft-mist inhalers, or nebulizers. Nebulized delivery is often preferable in patients who are elderly, are cognitively impaired, are unable to generate sufficient inspiratory force to use their inhaler, have difficulty coordinating hand-breath activity, are too dyspneic to hold their breath for a sufficient time, and/or may be acutely ill. Revefenacin, a once-daily long-acting muscarinic antagonist for nebulization recently approved by the US FDA for the treatment of patients with COPD, was discovered and developed using "duration and lung selectivity-by-design." This strategy selected a molecule with a high lung-selective index to maximize bronchodilation and limit systemic anti-muscarinic side effects. In early-phase clinical studies, revefenacin for nebulization led to a rapid onset of bronchodilation that was sustained for 24 hrs in patients with moderate to severe COPD. Revefenacin also demonstrated minimal systemic exposure and good tolerability in these studies. Statistically and clinically significant improvements in lung function (ie, peak and/or trough FEV1) relative to placebo were observed with revefenacin in Phase III clinical trials of up to 3 months in patients with moderate to very severe COPD. Revefenacin was well tolerated in Phase III clinical trials with a low incidence of systemic antimuscarinic adverse events, which is consistent with its lung-selective design. There was no evidence of an increased risk of major cardiovascular events. Patient-reported outcome data from clinical trials indicated statistically significant improvements in several disease-specific measures. Revefenacin 175 µg for nebulization provides an effective once-daily treatment option for patients with moderate to very severe COPD who require or prefer nebulized therapy.


Assuntos
Benzamidas/farmacologia , Carbamatos/farmacologia , Nebulizadores e Vaporizadores , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Broncodilatadores/farmacologia , Preparações de Ação Retardada/farmacologia , Humanos , Antagonistas Muscarínicos/farmacologia , Resultado do Tratamento
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