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QVA149 (Indacaterol/Glycopyrronium Fixed-Dose Combination): A Review of Its Use in Patients with Chronic Obstructive Pulmonary Disease.

QVA149 (indacaterol/glycopyrronium) [Xoterna(®) Breezhaler(®), Ultibro(®) Breezhaler(®)] is an inhaled fixed-dose combination of indacaterol (a long-acting selective β2-adrenergic receptor agonist [LABA]) and glycopyrronium (a long-acting muscarinic receptor antagonist [LAMA]) that has been approved in the EU and Japan for the symptomatic control of chronic obstructive pulmonary disease (COPD) in adults.

In phase III studies, QVA149 significantly improved bronchodilation versus indacaterol, glycopyrronium or tiotropium alone and the LABA/inhaled corticosteroid fixed-dose combination salmeterol/fluticasone. These improvements in lung function, which were rapid in onset and maintained during long-term treatment, were generally associated with significant improvements in dyspnoea, health status, COPD exacerbation risk, patient symptoms, and rescue medication use. The SHINE and ILLUMINATE studies in low (exacerbation) risk patients with moderate to severe disease suggest that QVA149 may offer more symptomatic relief than tiotropium and salmeterol/fluticasone. Similarly, the SPARK study in high (exacerbation) risk patients with severe or very severe disease showed that QVA149 was more effective than glycopyrronium in preventing moderate to severe exacerbations, and suggests that QVA149 may offer more symptomatic relief than LAMA monotherapy. Another phase III study comparing QVA149 with salmeterol/fluticasone in high-risk patients with moderate to very severe disease (FLAME) is ongoing. QVA149 is generally well tolerated, with no new safety signals identified compared with its monocomponents.

Bronchodilators remain central to the symptomatic management of COPD. When dual bronchodilation is indicated, QVA149 offers the convenience of two bronchodilators in a single inhaler coupled with a simple, once-daily dosing regimen that may encourage better treatment adherence. Therefore, it is a valuable option in the treatment of COPD.

Predictors of ICS/LABA prescribing in COPD patients: a study from general practice.

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Predictors of ICS/LABA prescribing in COPD patients: a study from general practice.

BMC Fam Pract. 2014 Mar 5;15(1):42

Authors: Drivenes E, Ostrem A, Melbye H

Abstract
BACKGROUND: A combination of inhaled corticosteroid and long-acting beta2 agonist (ICS/LABA) is used frequently to treat chronic obstructive pulmonary disease (COPD) patients. The aim of the study was to determine whether prescribing ICS/LABA to COPD patients in primary care in 2009/10 was within the GOLD guidelines and whether and to what degree patient characteristics were associated with prescription of these drugs by GPs.
METHODS: This was a cross-sectional study in seven Norwegian GP practices. Patients registered with a diagnosis of asthma or COPD in the previous five years were included.
RESULTS: Among the 376 patients included in the analysis, 149 patients had COPD, defined as a post-bronchodilator FEV1/FVC <0.7 and 55.6% of these patients were treated with ICS/LABA. The rate of prescribing was significantly higher in the COPD patients also diagnosed with asthma than in those with COPD as the only diagnosis, 66.7%, and 39.0%, respectively (P = 0.001). The prescribing rate in the latter subgroup would have been 18.6% if the 2007 GOLD guidelines had been followed. One or more exacerbations in the previous year was the strongest predictor of ICS/LABA prescribing in the COPD patients who were not registered with a concomitant diagnosis of asthma (OR 3.2, 95% CI 1.0-10.0) but this association was limited to the patients with severe disease (FEV1% predicted <50) (OR 13.5, 95% CI 1.8-101.1). Cardiovascular disease was associated with decreased ICS/LABA prescribing (OR 0.4, 95% CI 0.2-0.8) in the COPD group. A Kappa coefficient of 0.32 was found between the actual prescribing rate and that recommended in the 2007 GOLD guidelines.
CONCLUSION: Overprescribing of ICS/LABA for the COPD patients was shown. Previous exacerbation was a strong predictor of ICS/LABA prescribing only in patients with severe COPD. Because of the low emphasis on previous exacerbation when prescribing for COPD patients with mild to moderate disease, the actual prescribing rate agreed more closely with the GOLD guidelines from 2007 than with those published in 2011. Cardiovascular disease was associated with decreased prescribing, indicating that GPs adjust the treatment in cases with multimorbidity.

PMID: 24597538 [PubMed - as supplied by publisher]

Tiotropium in asthma: a systematic review.

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Tiotropium in asthma: a systematic review.

J Asthma Allergy. 2014;7:11-21

Authors: Befekadu E, Onofrei C, Colice GL

Abstract
INTRODUCTION: The objective of this paper is to systematically review the existing evidence of the effectiveness and safety profile of a long-acting inhaled muscarinic antagonist as add-on therapy in patients with asthma that is uncontrolled despite inhaled corticosteroid (ICS) use.
METHODS: With the assistance of two experienced research librarians, we searched Ovid MEDLINE/PubMed (1946 to September 12, 2013), the Cochrane Library review, and the TRIP database. The key search terms were "tiotropium and asthma." The search was limited to human data published in English. Included in the systematic review were all randomized controlled trials that evaluated the efficacy of tiotropium in patients with asthma. The clinical trials had to be at least 4 weeks in duration and to provide adequate information on clinically appropriate end points in asthma care (eg, change in lung function, exacerbation rates, and/or ICS dosing). Data on patient characteristics, study design, outcome measures, concomitant asthma medication, and adverse events were extracted from the full text of each included individual study. Marked heterogeneity of study design precluded statistical pooling of results for a meta-analysis. Consequently, only descriptive summaries of outcomes are provided.
RESULTS: Our database search retrieved 149 citations. We found five randomized controlled trials in humans that met our criteria for inclusion in the systematic review. We also found two open-label uncontrolled trials that were considered in the discussion. Each of the five included studies met the Consolidated Standards of Reporting Trials criteria for a well-designed randomized trial.
DISCUSSION: The five clinical studies included in this systematic review focused on evaluating the efficacy of tiotropium as add-on therapy to ICS or ICS in combination with a long-acting inhaled β2-agonist (LABA) in patients with uncontrolled moderate to severe persistent asthma. Tiotropium maintained lung function when ICSs were tapered and when an LABA was discontinued. Tiotropium improved lung function when added to ICS alone or ICS-LABA combination therapy. In the only trial to have compared the addition of tiotropium with doubling the dose of ICS, tiotropium provided significantly superior results. In trials in which the addition of tiotropium was compared with salmeterol, the beneficial effects of these two bronchodilators were similar. No safety concerns were found with use of tiotropium as add-on therapy.
CONCLUSION: Tiotropium may have a beneficial role in moderate to severe persistent asthma despite use of an ICS or ICS and LABA. Use of tiotropium as add-on therapy poses no safety concerns.

PMID: 24600237 [PubMed - as supplied by publisher]

[Health impact of exposure to pollens: A review of epidemiological studies.]

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[Health impact of exposure to pollens: A review of epidemiological studies.]

Rev Mal Respir. 2014 Feb;31(2):142-149

Authors: Caillaud D, Toloba Y, Raobison R, Besancenot JP, Thibaudon M, Martin S, Segala C

Abstract
The aim of this review is to describe the health impact of exposure to pollen based on recently published epidemiological studies. The methodology chapter, describes a review of the literature and outlines important elements of these studies: measurement of exposure to pollens, study types used, study populations and the health indicators related to pollen exposure. In this review, two types of studies have been used to assess the epidemiological evidence of short-term links between pollen exposure and hay fever or asthma. Ecological time-series studies use daily indicators of asthma exacerbations (emergency room admissions or hospitalizations), consultations for rhinitis or conjunctivitis, or anti-allergic drug consumption within general population. Panel studies relate measurements of pollen grain concentrations to nasal, ocular and bronchial symptom severity in a group of subjects sensitized to a specific pollen, monitored during the pollen season. In both cases, the studies show a relationship on a day-to-day basis between health indicators and daily rates of atmospheric pollen collected by a pollen trap. These studies take into account confounding factors, such as air pollution, weather factors and sometimes exposure to outdoor molds. Unlike earlier studies, more and more studies focus on the shape of the dose-response relationship and the lag between pollen exposure and symptoms. Only rarely, individual susceptibility factors, the clinical phenomenon of priming and polysensitization are reported. Thus, ecological time-series studies and panel studies assess respectively the impact of pollen exposure in the general population and in groups of sensitized patients. Using appropriate statistical tools, these studies provide insight into the shape of the dose-response relationship, with a potential threshold below which symptoms are absent, then a linear relationship for nasal, ocular and bronchial symptoms and a plateau where the symptoms do not increase despite the continued increase in pollen.

PMID: 24602681 [PubMed - as supplied by publisher]

Remodeling and fibrosis in chronic eosinophil inflammation.

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Remodeling and fibrosis in chronic eosinophil inflammation.

Dig Dis. 2014;32(1-2):15-21

Authors: Aceves SS

Abstract
Chronic eosinophilic inflammation has been associated with tissue remodeling in a number of disease states including the hypereosinophilic syndrome (HES), asthma, and, more recently, eosinophilic esophagitis (EoE). Remodeling occurs in the epithelial and subepithelial esophageal tissue, and includes basal zone hyperplasia, epithelial mesenchymal transition, fibrosis, angiogenesis, and smooth muscle hypertrophy/hyperplasia. Previously, research on the clinical impacts of tissue remodeling has been limited by a paucity of human tissue. However, in EoE, recurrent biopsies are required for diagnosis and management. As such, investigators are able to study the associations between tissue changes and clinical disease features. A number of profibrotic and proangiogenic factors are elevated in EoE, including TGF-β1, CCL-18, FGF-9, VEGF, and VCAM-1. Both eosinophils and mast cells produce a number of these factors. TGF-β1 appears to be a master regulator of end-organ dysfunction in EoE and can cause esophageal epithelial mesenchymal transition, fibrosis, and smooth muscle contraction. The requirement for eosinophils, the eosinophilopoietic interleukin, IL-5, and the canonical TGF-β1 signaling pathway for EoE-associated fibrosis, has been invoked using gene-deficient mice. The clinical consequences of eosinophil-associated tissue fibrosis can be devastating, such as endomyocardial fibrosis and heart failure in HES. In EoE, tissue remodeling appears to be the mechanism for multiple cardinal disease complications including esophageal rigidity, strictures, narrowing, and food impactions, as well as the clinical hallmark of dysphagia. Therapies that may be able to reduce or reverse EoE-associated remodeling include topical corticosteroids, anti-IL-5, and food antigen avoidance. © 2014 S. Karger AG, Basel.

PMID: 24603375 [PubMed - in process]

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