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Clinical Role of Dual Bronchodilation with an Indacaterol–Glycopyrronium Combination in the Management of COPD

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Clinical Role of Dual Bronchodilation with an Indacaterol–Glycopyrronium Combination in the Management of COPD Journal name: International Journal of COPD Article Designation: Review Year: 2015 Volume: 10 International Journal of COPD Dovepress Running head verso: Rossi et al Running head recto: Dual bronchodilation in management of COPD open access to scientific and medical research DOI: 55488 Open Access Full Text Article REVIEW Clinical role of dual bronchodilation with an indacaterol–glycopyrronium combination in the management of COPD: its impact on patient- related outcomes and quality of life Andrea Rossi1 Abstract: Chronic obstructive pulmonary disease (COPD) is the result of persistent and pro- Erika Zanardi2 gressive pathologic abnormalities in the small airways, most often associated with alveolar loss. Venerino Poletti3 Smoking cessation is the most effective intervention to slow down the progression of COPD. Mario Cazzola4 Long-acting inhaled bronchodilators are prescribed for the symptomatic relief at any stage of disease severity. For patients whose COPD cannot be not sufficiently controlled with long-acting 1Pulmonary Unit, University of Verona, Verona, 2Department of Respiratory bronchodilator monotherapy, international guidelines suggest the possibility of associating a and General Rehabilitation, ULSS 20, long-acting beta2 agonist (LABA) with a long-acting muscarinic antagonist (LAMA), ie, dual 3 For personal use only. Verona, Pulmonary Unit, GB Morgani bronchodilation. This is not a new concept as the combination of short-acting agents has been Hospital, AUSL 20, Forli, 4Pulmonary Unit, University of Rome, Tor Vergata, popular in the past. In recent years, several fixed-dose combinations containing a LAMA and Italy a LABA in a single inhaler have been approved by regulatory authorities in several countries. Among the new LAMA/LABA combinations, the fixed-dose combination of indacaterol 110 µg/ glycopyrronium 50 µg (QVA149) has been shown in a series of clinical trials to be as safe as the single components and placebo, and more effective than placebo and the single compo- nents with regard to lung function, symptoms, and patient-oriented outcomes. Furthermore, QVA149 achieved better bronchodilation than salmeterol 50 µg/fluticasone 500 µg twice daily. Compared with tiotropium, a well-recognized treatment for COPD, the percentage of patients that exceed the minimal clinical important difference for dyspnea and health-related quality of life measurements was superior with QVA149. Other patient-oriented outcomes, such as daily symptoms, night-time awakening, and use of rescue medication consistently favored QVA149. Finally, QVA149 was significantly superior to LAMAs for reducing all types of exacerbation. In conclusion, several years after introduction of dual bronchodilation, the fixed-dose combination of indacaterol 110 µg/glycopyrronium 50 µg in a single inhaler for once-daily administration via the Breezhaler® device (QVA149) has been demonstrated to be a safe and effective treat- International Journal of Chronic Obstructive Pulmonary Disease downloaded from https://www.dovepress.com/ by 54.70.40.11 on 18-Dec-2018 ment for COPD patients. Keywords: chronic obstructive pulmonary disease, long-acting bronchodilators, dual broncho- dilation, indacaterol, glycopyrronium, patient-oriented outcomes Introduction Chronic obstructive pulmonary disease (COPD) continues to be a major health and Correspondence: Andrea Rossi socioeconomic problem worldwide.1,2 It has been known for many years that COPD is Pulmonary Unit, University and General the result of persistent and progressive pathologic abnormalities in the small airways, Hospital Borgo Trento-Polo Confortini, P le Stefani 1, Verona 37126, Italy most often associated with alveolar loss.3–6 Cigarette smoking is the principal and most Tel +39 045 8122 439 widespread cause of this disorder, although other etiologic agents have been invoked.7–9 Fax +39 045 8122 049 Email [email protected] It has been reported that about 11% of patients with COPD are never-smokers.1 submit your manuscript | www.dovepress.com International Journal of COPD 2015:10 1383–1392 1383 Dovepress © 2015 Rossi et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further http://dx.doi.org/10.2147/COPD.S55488 permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php Powered by TCPDF (www.tcpdf.org) 1 / 1 Rossi et al Dovepress Abnormal spirometry, commonly defined by a reduction of predictor of the patient’s long-term response to treatment.25 the forced expiratory volume in one second/forced vital capac- However, several studies that have examined lung function 7 ity (FEV1/FVC) ratio below either 0.70 or the age-related “beyond FEV1” showed that reduction of lung hyperinfla- lower limit of normal,8–10 is the hallmark of the disease. Pro- tion is the main mechanism via which COPD patients derive gression of COPD is signaled by a faster than normal annual benefit over the entire span of severity.26–31 Improvement of 11–13 decline in FEV1 and FVC, as well as by an abnormal bronchial patency allows for better lung emptying and reset- increase in static lung volumes.14 The deterioration in lung ting of functional residual capacity at a lower lung volume.32 function is associated with worsening of dyspnea, increased These changes in lung function, which are not seen with the 15,16 rate and severity of exacerbations, a progressive inability FEV1, improve dynamic lung mechanics and determine bet- to cope with daily activity, and eventually premature death. ter exercise tolerance, decreased dyspnea, and even a lower International and national documents and guidelines7–9 exacerbation rate.31,33 give evidence-based recommendations for the management of COPD. At present, there is no cure for COPD. Smoking Why associate/combine cessation is by far the most effective way of slowing down bronchodilators? the progression of the disease and improving the chances of Airway tone is regulated by the parasympathetic and sympa- survival.11,13 However, some active pharmacologic treatments thetic nervous systems. The exact nature of the interactions have been shown to provide substantial benefits for patients between the two physiologic systems is not yet fully under- suffering from this disabling disorder.7–9 Long-acting bron- stood, but there is enough evidence to suggest that combining chodilators, such as long-acting beta2 agonists (LABAs) and beta2-agonists and muscarinic antagonists is pharmacologi- long-acting muscarinic antagonists (LAMAs), administered cally a good option for several reasons, which have been via inhalation, play a major role in the therapeutic manage- reviewed in detail recently.34,35 Briefly, we may assume that ment of COPD. In patients with frequent exacerbations, addi- addition of a muscarinic antagonist can reduce the bronchoc- tion of inhaled corticosteroids (ICS) to maintenance treatment onstricting effect of acetylcholine, release of which will have For personal use only. with a LABA has been suggested to further improve clinical been modified by the beta2-agonist, and thereby amplify the 17,18 outcomes. bronchodilation elicited by the same beta2-agonist through Recently, the combination of a LAMA and a LABA direct stimulation of beta2-adrenoceptors in smooth muscle. in a single inhaler has renewed the concept of dual bron- However, it has been suggested that crosstalk between mus- chodilation, which was popular in the past with the short- carinic receptors and beta2-adrenoceptors, causing functional acting agents.19–21 Current guidelines recommend combined antagonism at the level of the airway smooth muscle itself, LAMA/LABA use if symptoms are not improved by a seems more likely to be of importance.36,37 It seems reasonable single agent.7,9 to hypothesize that targeting bronchoconstriction through This paper reviews the effects of one of the newly mar- two distinct mechanisms should optimize the bronchodilator keted LAMA and LABA combinations, ie, the fixed-dose response and help to overcome the interpatient and intrapa- combination (FDC) of indacaterol 110 µg/glycopyrronium tient variability in bronchomotor tone associated with airway 50 µg in one inhaler (Breezhaler®) administered once daily obstruction.38 In addition, some in vitro studies suggest a (ie, QVA149) on patient-related outcomes (PROs), which possible synergistic, and not simply additive, effect when have gained increasing attention in clinical trials.22 the two active agents reach the cell target together.38 International Journal of Chronic Obstructive Pulmonary Disease downloaded from https://www.dovepress.com/ by 54.70.40.11 on 18-Dec-2018 Complex effect of bronchodilators Dual bronchodilation in COPD The initial trials on dual bronchodilation were performed Inhaled bronchodilators (short-acting and then long-acting) with short-acting bronchodilators.19–21,39 In some studies, have been widely used for many years for symptomatic administration of one drug was followed by inhalation of relief in COPD patients at any stage of disease severity.7–9 the other.40 In other studies, an FDC was more effective in Although in large-scale population studies, the
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