Saving lives in COPD requires a proactive approach

As someone who has dedicated their career to advancing respiratory science, I am troubled that COPD, a disease which caused three million fatalities in a single year¹ – more than breast and lung cancer combined² – remains under-prioritized, underfunded, and undertreated.^3-5

On average, 368 people globally die from COPD every hour.^1,6 There’s no time to lose in tackling this major public health threat.

COPD is a heterogenous lung condition characterized by chronic respiratory symptoms due to abnormalities of the airways, including emphysema and chronic bronchitis, that cause progressive airflow obstruction.^1,7 The patient, health system and societal burdens of COPD are monumental;^1,4,7-12 by 2030, costs associated with the disease are expected to reach $4.8TN.⁸

Despite advances in treatment, a large patient population is uncontrolled on current treatment options.^7,13,14

Our commitment to driving scientific understanding in COPD makes me hopeful that the groundbreaking research being carried out by AstraZeneca to further our knowledge of COPD will one day mean we can turn the tables on this disease so that it is no longer a leading cause of death. We are focused on delivering transformative change in COPD, pursuing a full, integrated portfolio across inhaled, biologics, and newer investigative moderate-severe add-on (“pre-biologic”) medicines, to provide support across the COPD patient journey and deliver a new wave of innovation – from primary through to specialty care.

Deepening our understanding of COPD meets the needs of a broad population There are many mechanisms involved in COPD meaning there is no ‘one size fits all’ approach to treatment for the nearly 400 million people impacted.15 At AstraZeneca, we are pursuing key pathways to deepen our understanding of COPD so we can enrich our portfolio with medicines for the future and augment our current portfolio. Key areas of research include investigating epithelial science to understand the critical role airway epithelium and inflammatory cytokine cascades play in the clinical features of COPD.16 The role of myeloperoxidase (MPO) is also being evaluated, as increased levels of MPO have been detected in the airways of patients with COPD, triggering oxidative stress which leads to lung inflammation, damage, and cardiovascular pathophysiology. Increased MPO in the sputum has been shown by our scientists to be associated with an increased risk of COPD exacerbations.17-19 Separately, we are also investigating opportunities to reduce COPD exacerbation risk across a broad range of blood eosinophil counts. We are committed to meeting the needs of patients across the disease spectrum, so that no patient is left behind.

While we look optimistically to the future of innovation in COPD, a preventative approach must be taken to address COPD today. Improving patient prognosis in COPD requires a proactive mindset, moving away from the current approach of escalating therapy only after treatment failure.^7,20 An approach that prioritizes prompt therapeutic intervention to improve outcomes, lowers the risk associated with COPD in and beyond the lungs, and reduces mortality.^7,21

Addressing cardiopulmonary risk can save lives The mechanisms of COPD put even newly diagnosed patients at an elevated risk of both lung and heart events, which is known as cardiopulmonary risk.22,23 These events can be severe or even fatal.23-27 In fact, in patients with COPD, pulmonary and cardiac events are the most common reasons for death,28,29 and the risk is significantly increased after a COPD exacerbation.30-32 Shockingly, one single exacerbation doubles the risk of a heart attack in the first 5 days post-exacerbation, and increases the risk of future exacerbations, stroke, hospitalization, and cardiopulmonary-related death.25,33,34 According to data from AstraZeneca’s EXACOS-CV studies, this increased risk may persist for up to one year following a COPD exacerbation.23,32,35-37 Only 50% of patients were alive within 3.6 years of their first severe exacerbation.27 It’s clear: preventing COPD exacerbations can help address cardiopulmonary risk as well as reduce the risk of avoidable death.7,21,38-40 MeiLan Han, MD, MS: “A change in clinical practice is urgently needed. The 2024 GOLD Report calls for a more proactive therapeutic approach to COPD and outlines mortality reduction as a key treatment goal. Achieving such a proactive mindset will require accelerated action from the clinical community against the significant impact of exacerbations, and greater focus on the diverse cardiopulmonary risks associated with COPD.”

Driving future innovation in COPD

As a pulmonologist with a PhD in Clinical Pharmacology, I – along with our team of scientists – am motivated by a commitment to:

• Providing optimized care for symptomatic patients with treatment that has the potential to reduce cardiopulmonary risk
• Delivering interventions that address the underlying drivers of severe disease
• Exploring the pre-biologics space to support the millions for whom biologics are unsuitable, but whose conditions remain uncontrolled with standard-of-care therapies

Now is the time to act. Embracing a proactive approach to COPD is the key to preventing exacerbations and addressing cardiopulmonary risk to save lives.^7,21 We must not lose sight of the innovation that’s required to transform care for the future.

For more information, visit ActonCOPD.com (initiated, developed, and funded by AstraZeneca in collaboration with a steering committee comprised of healthcare professionals).

References

1. WHO. Factsheet. Chronic obstructive pulmonary disease (COPD). Available at: Chronic obstructive pulmonary disease (COPD) (who.int) [Last accessed: April 2024].

2. World Health Organization. Global Health Estimates 2019: Deaths by Cause, Age, Sex, by Country and by Region, 2000-2019. Global Summary Estimates. Geneva (2020) Available at https://www.who.int/data/gho/data/themes/mortality-and-global-health-estimates/ghe-leading-causes-of-death [Last accessed: April 2024].

3. Quaderi, S. A., & Hurst, J. R. The unmet global burden of COPD. Glob Health Epidemiol Genom, 2018; 3, e4.

4. Ballreich JM, Gross CP, Powe NR et al. Allocation of National Institutes of Health Funding by Disease Category in 2008 and 2019. JAMA Network Open. 2021; 4(1): e2034890.

5. Make B, Dutro MP, Paulose-Ram R, et al. Undertreatment of COPD: a retrospective analysis of US managed care and Medicare patients. Int J Chron Obstruc Pulmon Dis. 2012; 7: 1.

6. AstraZeneca Data on File: REF-225658.

7. GOLD. Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2024. [Online]. Available at: https://goldcopd.org/2024-gold-report/ [Last accessed: April 2024]

8. Bloom DE, Cafiero ET, Jane-Llopis E, et al. The Global Economic Burden of Noncommunicable Diseases. Geneva: World Economic Forum; 2011. Available at: https://www.hsph.harvard.edu/pgda/wp-content/uploads/sites/1288/2013/10/PGDA_WP_87.pdf [Last accessed: April 2024].

9. May SM, Li JTC. Burden of chronic obstructive pulmonary disease: healthcare costs and beyond. Allergy Asthma Proc. 2015; 36:4 –10.

10. Halbert RJ, Natoli JL, Gano A, et al. Global burden of COPD: systematic review and meta-analysis. Eur Respir Journ 2006 28: 523-532.

11. Nakken N, Janssen DJA, van den Bogaart EHA, et al. Informal caregivers of patients with COPD: Home Sweet Home? European Respiratory Review 2015 24: 498-504.

12. Iheanacho I, Zhang S, King D, et al. Economic Burden of Chronic Obstructive Pulmonary Disease (COPD): A Systematic Literature Review. Int J Chron Obstruct Pulmon Dis. 2020;15:439-460.

13. Soler-Cataluña JJ, Huerta A, Almagro P, et al. Lack of clinical control in COPD patients depending on the target and therapeutic option. Int J Chron Obstruc Pulmon Dis (2023) 18: 1367-1376.

14. Müllerová H, Meeraus WH, Galkin DV, et al. Clinical burden of illness among patents with severe eosinophilic COPD. Int J Chron Obstruc Pulmon Dis (2019) 14: 741-755.

15. Adeloye D, Song P, Zhu Y, et al. Global, regional, and national prevalence of, and risk factors for, chronic obstructive pulmonary disease (COPD) in 2019: a systematic review and modelling analysis. Lancet Respir Med. (2022) Vol 10(5); 447-458.

16. Raby KL, Michaeloudes C, Tonkin J,et al. Mechanisms of airway epithelial injury and abnormal repair in asthma and COPD. Front Immunol. 2023;14:1201658.

17. Cockayne DA, Cheng DT, Waschki B, et al. Systemic biomarkers of neutrophilic inflammation, tissue injury and repair in COPD patients with differing levels of disease severity. PLoS One. 2012;7(6):e38629.

18. Park HY, Man SF, Tashkin D, et al. The relation of serum myeloperoxidase to disease progression and mortality in patients with chronic obstructive pulmonary disease (COPD). PLoS One. 2013;8(4):e61315. Published 2013 Apr 18. doi:10.1371/journal.pone.0061315.

19. Rosengren S, Tangefjord S, de Palo G, et al. Airway myeloperoxidase (MPO) is associated with increased risk of exacerbations in COPD. Eur Respir J 2022; 60: Suppl. 66.

20. Wilkinson TM, Donaldson GC, Hurst JR, et al. Early therapy improves outcomes of exacerbations of chronic obstructive pulmonary disease. Am J Respir 2004;169:1298-303.

21. Stolz D., Mkorombindo T., Schumann D., et al. Towards the elimination of chronic obstructive pulmonary disease: a Lancet Commission. The Lancet Commissions. Vol.400 Issue 10356 (Sept. 2022); pp.921-972.

22. Rabe KF, Hurst JR, Suissa S. Cardiovascular disease and COPD: dangerous liaisons? Eur Respir Rev. 2018 Oct 3;27(149):180056.

23. Swart K, Baak B, Lemmens L, et al. Risk of cardiovascular events after an exacerbation of chronic obstructive pulmonary disease: results from the EXACOS-CV cohort study using the PHARMO Data Network in the Netherlands. Respir Res. (2023) Vol 24: 293.

24. Ho TW, Tsai YJ, Ruan SY, et al. In-Hospital and One-Year Mortality and Their Predictors in Patients Hospitalized for First-Ever Chronic Obstructive Pulmonary Disease Exacerbations: A Nationwide Population-Based Study. PLOS ONE. 2014; 9 (12): e114866.

25. Donaldson GC, Hurst JR, Smith CJ, et al. Increased risk of myocardial infarction and stroke following exacerbation of COPD. Chest. 2010;137:1091-1097;9-2029.

26. Watz H, Tetzlaff K, Magnussen H, et al. Spirometric changes during exacerbations of COPD: A post hoc analysis of the WISDOM trial. Respir Res. 2018;19(1):251.

27. Suissa S, Dell’Aniello S, Ernst P. et al. Long-term natural history of chronic obstructive pulmonary disease: severe exacerbations and mortality. Thorax. 2012;67(11):957-963.

28. García-Sanz MT, Cánive-Gómez JC, Senín-Rial L, et al. One-year and long-term mortality in patients hospitalized for chronic obstructive pulmonary disease. J Thorac Dis. 2017; 9 (3): 636‐ doi:10.21037/jtd.2017.03.34.

29. Mannino DM, Doherty DE, Buist AS. Global Initiative on Obstructive Lung Disease (GOLD) classification of lung disease and mortality: findings from the Atherosclerosis Risk in Communities (ARIC) study. Respir Med. 2006;100: pp.115-122.

30. Kunisaki KM, Dransfield MT, Anderson JA, et al. Exacerbations of Chronic Obstructive Pulmonary Disease and Cardiac Events. A Post Hoc Cohort Analysis from the SUMMIT Randomized Clinical Trial. AM J Respir Crit Care Med, 2018;198(1):pp.51-57.

31. Halpin DMG, Decramer M, Celli BR, et al. Effect of a single exacerbation on decline in lung function in COPD. Respir Med 2017; 128: 85-91.

32. Vogelmeier CF, Simons S, Garbe E, et al. Increased risk of severe cardiovascular events following exacerbations of COPD: a multi-database cohort study [Poster]. Presented at the European Respiratory Society Congress 2023 (9-13 September).

33. Whittaker H, Rubino A, Mullerova H, et al. Frequency and Severity of Exacerbations of COPD Associated with Future Risk of Exacerbations and Mortality: A UK Routine Health Care Data Study. Int J Chron Obstruct Pulmon Dis. 2022;17:427-437.

34. Rothnie KJ, Müllerová H, Smeeth L, et al. Natural History of Chronic Obstructive Pulmonary Disease Exacerbations in a General Practice-based Population with Chronic Obstructive Pulmonary Disease. Am J Resp Crit Care Med. 2018;198(4): pp.464-471.

35. Hawkins NM, Vogelmeier CF, Simons SO, et al. Increased risk of decompensated heart failure, acute coronary syndrome, arrhythmias and ischaemic stroke following exacerbations of COPD: results from a multi-database cohort study. [Poster] Presented at the European Society of Cardiology Congress 2023 (25-29 August).

36. Hawkins NM, Nordon C, Rhodes K, et al. Heightened long-term cardiovascular risks after exacerbation of chronic obstructive pulmonary disease. Heart. 2024 Jan 5:heartjnl-2023-323487. doi: 10.1136/heartjnl-2023-323487. Epub ahead of print. PMID: 38182279.

37. Graul EL, Nordon C, Rhodes K, et al. Temporal Risk of Non-Fatal Cardiovascular Events Post COPD Exacerbation: A Population-based study. Am J Resp Crit Care Med. 2023.

38. Rabe KF, Martinez FJ, Ferguson GT, et al. Triple Inhaled Therapy at Two Glucocorticoid Doses in Moderate-to-Very Severe COPD. N Engl J Med 2020; 383: pp.35-48.

39. Pollack, M, Tkacz, J, Schinkel, J. et al. Exacerbations and real-world outcomes (EROS) among patients with COPD receiving single inhaler triple therapy of budesonide/glycopyrrolate/formoterol fumarate [Poster Discussion]. Presented at the American Thoracic Society International Conference 2023 (19-24 May).

40. Viniol C, Volgelmeier CF. Exacerbations of COPD. Eur Respir Rev. 2018 Mar 31; 27(147): 170103.

Veeva ID: Z4-63119
Date of Preparation: April 2024