Clinical Effectiveness And Safety Of Glycopyrronium In Chronic Obstructive Pulmonary Disease And Asthma Copd Overlap: Acos Study
Volume 4 - Issue 5, May 2020 Edition
[Download Full Paper]
Prabhudesai PP , Singh BP, Bhattacharya PS, Katiyar S, Korukonda K
Asthma COPD Overlap, Chronic obstructive pulmonary disease, frequent exacerbator, Glycopyrronium, Non-smoker.
Introduction: The burden of Asthma-COPD Overlap (ACO) Syndrome is evolving especially in light of growing burden for nonsmoking risk factors in India. Glycopyrronium add on therapy offers quick and complimentary bronchodilation and anti-inflammatory actions in poorly controlled COPD or ACO. Material and Methods: A prospective, observational, case control, drug utilization study was conducted at four centers during Jan’ to Dec’ 18 for COPD and ACO cases defined as per GOLD and Roundtable ATS recommendations respectively were enrolled in 1:1 ratio at four centers after IRB approval, written informed consent and Clinical trial registry of India registration (CTRI/2017/09/009845). A study sample size (n=160) was based on assessment of primary endpoint for a pre-bronchodilator FEV1 difference of 50% between the two groups of ACO and COPD receiving Glycopyrronium add on therapy compared to baseline values at 12 weeks with a dropout rate of 25% Results: 128 COPD (n=64) and ACO (n=64) cases with at least one prior exacerbation were randomized to Glycopyrronium (50 mcg, once a day) ‘add-on’ with FORM6/BUD200 mcg, twice a day for 12 weeks. Baseline demographics, Male/Female (119/09); Age 59.911.1y; Wt 59.113.7kg; FEV1 49.9%15.8; Exacerbation ≥2/y, [82(64%)]; CAT (19.48.3); Smoker (90, 70.3%), Non-smoker (38, 29.7%). prebronchodilator FEV1 improvement difference between COPD and ACO groups met the pre-defined difference of 50% improvement at 12 weeks as 6.412.4% (127.1248 ml, p<0.03). Post-hoc analyses for COPD and ACO Smoker frequent exacerbators showed prebronchodilator FEV1 (change) 123.2356.4 ml (p<0.0001) and 320.9335.3 ml (p<0.0001) respectively. In COPD and ACO non-smoker frequent exacerbators pre-dose FEV1 (change) of 216.2354.9 ml (p=0.001) and 402.3406.1 ml (p=0.02) was observed respectively. Intent to treat analyses showed TEAEs (7, 4.3%) of mild to moderate intensity with none requiring any treatment withdrawal. Conclusion: Glycopyrronium 50 mcg ‘add-on’ therapy offers incremental bronchodilation that is meaningfully clinically significant (MCID) in poorly controlled symptomatic Severe COPD and ACO.
. L. Dandona, “India State-Level Disease Burden Initiative CRD Collaborators*. The burden of chronic respiratory diseases and their heterogeneity across the states of India: the Global Burden of Disease Study 1990–2016,” Lancet Global Health, 6, pp.e1363–74, 2018.
. D.D. Sin, M. Miravitlles, D.M. Mannino, et al, “What is asthma-COPD overlap syndrome? Towards a consensus definition from a round table discussion,” Eur Respir J., 48, pp. 664-73, 2016.
. V. Plaza, F. Álvarez, M. Calle, C. Casanova, B.G. Cosío, A. López-Viña, “Consensus on the Asthma–COPD Overlap (ACO) Between the Spanish COPD Guidelines (GesEPOC) and the Spanish Guidelines on the Management of Asthma (GEMA),” Arch Bronconeumol., 53(8), pp. 443–449, 2017.
. Global initiative on Chronic obstructive lung disease, “Pocket Guide To COPD Diagnosis, Management, And Prevention. A Guide for Health Care Professionals. GOLD 2019 Report,” Available: https://goldcopd.org/wp-content/uploads/2018/11/GOLD-2019-v1.7-FINAL-14Nov2018-WMS.pdf. [Accessed: Jul. 28, 2019].
. D. Singh, A. Papi, M. Corradi, et al, “Single inhaler triple therapy versus inhaled corticosteroid plus long-acting β2-agonist therapy for chronic obstructive pulmonary disease (TRILOGY): a double-blind, parallel group, randomised controlled trial,” Lancet, 388, pp. 963–73, 2016.
. A. Papi, J. Vestbo, L. Fabbri L, et al, “Extrafine inhaled triple therapy versus dual bronchodilator therapy in chronic obstructive pulmonary disease (TRIBUTE): a double-blind, parallel group, randomised controlled trial,” Lancet, 391(10125), pp. 1076-1084, 2018.
. L.L. Shen, Y.N. Liu, H.J. Shen, et al, “Inhalation of glycopyrronium inhibits cigarette smoke-induced acute lung inflammation in a murine model of COPD,” Int. Immunopharmacol., 18(2), pp. 358-364, 2014.
. J.A. Wedzicha, D. Banerji, K.R. Chapman, et al, “Indacaterol-Glycopyrronium versus Salmeterol-Fluticasone for COP,” N. Engl. J. Med., 374(23), pp. 2222-2234, 2016.
. N. Baxter, K. Gruffydd-Jones, V. Mak, I. Small, “Primary care respiratory society. Evaluation of appropriateness of inhaled corticosteroid (ICS) therapy in COPD and guidance on ICS withdrawal,” Available: https://www.pcrs-uk.org/resource/stepping-down-inhaled-corticosteroids-copd SteppingDownICS_FINAL5.pdf. [Accessed: Jan. 28, 2020]
. J. Vestbo, A. Papi, M. Corradi, “Single inhaler extrafine triple therapy versus long-acting muscarinic antagonist therapy for chronic obstructive pulmonary disease (TRINITY): a double-blind, parallel group, randomised controlled trial,” Lancet, 389(10082), pp. 1919-1929, 2017.
. G. Zeng, B. Sun, N. Zhong, “Non-smoking-related chronic obstructive pulmonary disease: a neglected entity?,” Respirology, 17(6), pp. 908-912, 2012.
. D. Behera, S.K. Jindal, “Respiratory symptoms in Indian women using domestic cooking fuels,” Chest, 100(2), pp. 385-388, 1991.
. P.A. Mahesh, B.S. Jayaraj, A.K. Prabhakar, S.K. Chaya, and R. Vijaysimha R, “Identification of a threshold for biomass exposure index for chronic bronchitis in rural women of Mysore district, Karnataka, India,” Indian J. Med. Res. 137(1): 87–94, 2013.
. S. Lainez, I. Court-Fortune, P. Vercherin, L. Falchero, T. Didi, “Clinical ACO phenotypes: Description of a heterogeneous entity,” Respir. Med. Case Rep., 28, pp. 100929, 2019.
. A.N. Aggarwal, R. Agarwal, S. Dhooria, et al, “Joint Indian Chest Society-National College of Chest Physicians (India) guidelines for spirometry,” Lung India, 36(Suppl 1), pp. S1–S35, 2019.
. K. Nazarenko, Y. Feschenko, L. Lashyna, “The effect of tiotropium bromide on lung function parameters in patients with asthma- COPD overlap syndrome,” European Respiratory Journal, 48, pp. PA3372, 2016.
. H. Xu, X. Lu, “Inhaled Glucocorticoid with or without Tiotropium Bromide for Asthma-Chronic Obstructive Pulmonary Disease Overlap Syndrome,” J. Coll. Physicians Surg. Pak., 29(3), pp. 249-252, 2019.