Comparative studies of dual bronchodilation in COPD


Dual bronchodilation therapy is becoming the cornerstone for the treatment of COPD because the clinical benefits of LABA/LAMA fixed-dose combinations (FDCs) are now extensively established. Therefore, it not surprising that a number of LAMA/LABA combinations in a single inhaler have now been approved for clinical use as treatments for patients with COPD. Regrettably, very few head-to-head studies between all of the available LABA/LAMA FDCs have been carried out. This makes choosing the most appropriate FDC difficult. Comparative effectiveness research that also uses conventional meta-analyses to compare different care strategies can help generate useful information. A bidimensional comparative analysis across LAMA/LABA FDCs has suggested constant superiority for tiotropium/olodaterol. However, considering that there is not an equivalent amount of evidence on efficacy outcomes for all LAMA/LABA FDCs, a proper comparison between the different LAMA/LABA FDCs cannot be made yet, and the information available is still rather inconsistent.



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Singh D, Agusti A, Anzueto A, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease: the GOLD science committee report 2019. Eur Respir J 2019;53:1900164.

Cazzola M, Rogliani P, Stolz D, Matera MG. Pharmacological treatment and current controversies in COPD. F1000Res 2019;8:F1000 Faculty Rev-1533.

Dransfield MT, Bailey W, Crater G, et al. Disease severity and symptoms among patients receiving monotherapy for COPD. Prim Care Respir J 2011;20:46-53.

Cazzola M, Page CP, Calzetta L, Matera MG. Pharmacology and therapeutics of bronchodilators. Pharmacol Rev 2012;64:450-504.

Cazzola M, Page CP, Rogliani P, Matera MG. β2-agonist therapy in lung disease. Am J Respir Crit Care Med 2013;187:690-6.

Matera MG, Page CP, Calzetta L, et al. Pharmacology and therapeutics of bronchodilators revisited. Pharmacol Rev 2020;72:218-52.

Cazzola M, Page C, Matera MG. Long-acting muscarinic receptor antagonists for the treatment of respiratory disease. Pulm Pharmacol Ther 2013;26:307-17.

Stolz D, Cazzola M. Characterising the cardiovascular safety profile of inhaled muscarinic receptor antagonists. In: Martínez-García MÁ, Pépin J-L, Cazzola M, editors. Cardiovascular complications of respiratory disorders (ERS Monograph). Sheffield, European Respiratory Society, 2020; p. 238-50.

Cazzola M, Segreti A, Stirpe E, et al. Effect of an additional dose of indacaterol in COPD patients under regular treatment with indacaterol. Respir Med 2013;107:107-11.

Cazzola M, Brusasco V, Centanni S, et al. Project PriMo: sharing principles and practices of bronchodilator therapy monitoring in COPD: a consensus initiative for optimizing therapeutic appropriateness among Italian specialists. Pulm Pharmacol Ther 2013;26:218-28.

Calzetta L, Rogliani P, Matera MG, Cazzola M. A systematic review with meta-analysis of dual bronchodilation with LAMA/LABA for the treatment of stable COPD. Chest 2016;149:1181-96.

Calzetta L, Ora J, Cavalli F, et al. Impact of LABA/LAMA combination on exercise endurance and lung hyperinflation in COPD: A pair-wise and network meta-analysis. Respir Med 2017;129:189-98.

Calzetta L, Matera MG, Cazzola M. Pharmacological interaction between LABAs and LAMAs in the airways: optimizing synergy. Eur J Pharmacol 2015;761:168-73.

Calzetta L, Matera MG, Cazzola M. Pharmacological mechanisms leading to synergy in fixed-dose dual bronchodilator therapy. Curr Opin Pharmacol 2018;40:95-103.

Wedzicha JA, Decramer M, Ficker JH, et al. Analysis of chronic obstructive pulmonary disease exacerbations with the dual bronchodilator QVA149 compared with glycopyrronium and tiotropium (SPARK): a randomised, double-blind, parallel-group study. Lancet Respir Med 2013;1:199-209.

Beeh KM, Burgel PR, Franssen FME, et al. How do dual long-acting bronchodilators prevent exacerbations of chronic obstructive pulmonary disease? Am J Respir Crit Care Med 2017;196:139-49.

Cazzola M, Calzetta L, Puxeddu E, et al. Pharmacological characterisation of the interaction between glycopyrronium bromide and indacaterol fumarate in human isolated bronchi, small airways and bronchial epithelial cells. Respir Res 2016;17:70.

Yamada M, Ichinose M. The cholinergic pathways in inflammation: a potential pharmacotherapeutic target for COPD. Front Pharmacol 2018;9:1426.

Calzetta L, Matera MG, Rogliani P, Cazzola M. Dual LABA/LAMA bronchodilators in chronic obstructive pulmonary disease: why, when, and how. Expert Rev Respir Med 2018;12:261-4.

Cazzola M, Calzetta L, Ora J, et al. Searching for the synergistic effect between aclidinium and formoterol: From bench to bedside. Respir Med 2015;109:1305-11.

Cazzola M, Calzetta L, Segreti A, et al. Translational study searching for synergy between glycopyrronium and indacaterol. COPD 2015;12:175-81.

Cazzola M, Calzetta L, Page CP, et al. Pharmacological characterization of the interaction between aclidinium bromide and formoterol fumarate on human isolated bronchi. Eur J Pharmacol 2014;745:135-43.

Calzetta L, Rogliani P, Facciolo F, et al. Pharmacological characterization of the interaction between umeclidinium and vilanterol in human bronchi. Eur J Pharmacol 2017;812:147-54.

Calzetta L, Rogliani P, Page C, et al. Pharmacological characterization of the interaction between tiotropium bromide and olodaterol on human bronchi and small airways. Pulm Pharmacol Ther 2019;56:39-50.

Cazzola M, Matera MG. POINT: Should LAMA/LABA combination therapy be used as initial maintenance treatment for COPD? Yes. Chest 2018;154:746-8.

Cazzola M, Segreti A, Rogliani P. Comparative effectiveness of drugs for chronic obstructive pulmonary disease. Drugs Today (Barc) 2012;48:785-94.

Kerwin E, Ferguson GT, Sanjar S, et al. Dual bronchodilation with indacaterol maleate/glycopyrronium bromide compared with umeclidinium bromide/vilanterol in patients with moderate-to-severe COPD: results from two randomized, controlled, cross-over studies. Lung 2017;195:739-47.

Feldman GJ, Sousa AR, Lipson DA, et al. Comparative efficacy of once-daily umeclidinium/vilanterol and tiotropium/olodaterol therapy in symptomatic chronic obstructive pulmonary disease: a randomized study. Adv Ther 2017;34:2518-33.

Cazzola M, Rogliani P. Comparative effectiveness of indacaterol/glycopyrronium in the treatment of chronic obstructive pulmonary disease. J Comp Eff Res 2017;6:627-36.

Berenbaum MC. Isobolographic, algebraic, and search methods in the analysis of multiagent synergy. J Am Coll Toxicol 1988;7:927-38.

Calzetta L, Matera MG, Cazzola M, Rogliani P. Optimizing the development strategy of combination therapy in respiratory medicine: from isolated airways to patients. Adv Ther 2019;36:3291-8.

Rogliani P, Calzetta L, Braido F, et al. LABA/LAMA fixed-dose combinations in patients with COPD: a systematic review. Int J Chron Obstruct Pulmon Dis 2018;13:3115-30.

Rogliani P, Matera MG, Ritondo BL, et al. Efficacy and cardiovascular safety profile of dual bronchodilation therapy in chronic obstructive pulmonary disease: A bidimensional comparative analysis across fixed-dose combinations. Pulm Pharmacol Ther 2019;59:101841.

Salanti G, Ades AE, Ioannidis JP. Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: an overview and tutorial. J Clin Epidemiol 2011;64:163-71.

Calzetta L, Rogliani P, Page C, et al. Pharmacological characterization of the interaction between tiotropium bromide and olodaterol on human bronchi and small airways. Pulm Pharmacol Ther 2019;56:39-50.

Goldoni M, Johansson C. A mathematical approach to study combined effects of toxicants in vitro: evaluation of the Bliss independence criterion and the Loewe additivity model. Toxicol In Vitro 2007;21:759-69.

Benfante A, Braido F, Scichilone N. The anti-inflammatory properties of tiotropium. Lancet Respir Med 2018;6:e37.

Calverley PMA, Anzueto AR, Carter K, et al. Tiotropium and olodaterol in the prevention of chronic obstructive pulmonary disease exacerbations (DYNAGITO): a double-blind, randomised, parallel-group, active-controlled trial. Lancet Respir Med 2018;6:337-44.

Rogliani P, Calzetta L, Cazzola M. Is ICS-LAMA an alternative option to treat patients with COPD? Lancet Respir Med 2018;6:316-7.

Cazzola M, Rogliani P, Novelli L, Matera MG. Inhaled corticosteroids for chronic obstructive pulmonary disease. Expert Opin Pharmacother 2013;14:2489-99.

Anzalone G, Gagliardo R, Bucchieri F, et al. IL-17A induces chromatin remodeling promoting IL-8 release in bronchial epithelial cells: effect of tiotropium. Life Sci 2016;152:107-16.

Profita M, Bonanno A, Montalbano AM, et al. β2 long-acting and anticholinergic drugs control TGF-β1-mediated neutrophilic inflammation in COPD. Biochim Biophys Acta 2012;1822:1079-89.

Wedzicha JA, Buhl R, Singh D, et al. Tiotropium/olodaterol decreases exacerbation rates compared with tiotropium in a range of patients with COPD: pooled analysis of the TONADO®/DYNAGITO® trials. Adv Ther 2020;37:4266-79.

Singh S, Loke YK, Enright PL, Furberg CD. Mortality associated with tiotropium mist inhaler in patients with chronic obstructive pulmonary disease: systematic review and meta-analysis of randomised controlled trials. BMJ 2011;342:d3215.

Rogliani P, Ritondo BL, Zerillo B, et al. Adding a second bronchodilator in COPD: A meta-analysis on the risk of specific cardiovascular serious adverse events of tiotropium/olodaterol fixed-dose combination. COPD 2020;17:215-23.

Maltais F, Buhl R, Koch A, et al. β-blockers in COPD: a cohort study from the TONADO research program. Chest 2018;153:1315-25.

Matera MG, Calzetta L, Cazzola M. β-Adrenoceptor modulation in chronic obstructive pulmonary disease: present and future perspectives. Drugs 2013;73:1653-63.

Cazzola M, Calzetta L, Rinaldi B, et al. Management of chronic obstructive pulmonary disease in patients with cardiovascular diseases. Drugs 2017;77:721-32.

Cazzola M, Matera MG. Combining dual bronchodilation and β-blockade in patients with an overlap between COPD and cardiovascular diseases. Chest 2018;153:1289-91.

Rinaldi B, Donniacuo M, Sodano L, et al. Effects of chronic treatment with the new ultra-long-acting β2-adrenoceptor agonist indacaterol alone or in combination with the β-adrenoceptor blocker metoprolol on cardiac remodelling. Br J Pharmacol 2015;172:3627-37.

Miravitlles M, Baek S, Vithlani V, Lad R. Optimal bronchodilation for COPD patients: are all long-acting β2-agonist/long-acting muscarinic antagonists the same? Tuberc Respir Dis (Seoul) 2018;81:198-215.

Pneumology - Editorial
Dual bronchodilators, COPD, comparative effectiveness studies
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How to Cite
Cazzola, M., Matera, M. G., Rogliani, P., & Calzetta, L. (2021). Comparative studies of dual bronchodilation in COPD. Monaldi Archives for Chest Disease, 91(1).