THE EFFICACY OF BIOLOGICAL TREATMENT METHODS IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE PATIENTS; SYSTEMATIC REVIEW
Main Article Content
Keywords
Chronic obstructive pulmonary disease; Biologic therapy; Eosinophilic inflammation; Dupilumab; Mepolizumab; Benralizumab; Tezepelumab
Abstract
Background: Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disorder characterized by airflow obstruction and persistent inflammation, result in frequent exacerbations and reduced quality of life. Patients with moderate to severe COPD continue to experience disease progression with regular treatments. Biologic therapies to a specific immune pathways were developed through the identification of eosinophilic and type 2 inflammatory phenotypes. This study aims to evaluate the efficacy and safety of biologic therapies to decrease exacerbations and improve clinical outcomes in patients with moderate to severe COPD.
Methods: we conduct a systematic search in electronic databases (PubMed, Scopus, and Google Scholar) for randomized controlled trials (RCTs) published between 2014 and 2024. Studies included adult COPD patients (≥40 years) treated with biologics targeting IL-5, IL-4/13, IL-1, or TSLP. The Cochrane Risk of Bias 2 tool was used to assess study quality. Data extraction and screening were performed independently by two authors.
Results: Seven RCTs were included, examining biologic treatrmet (dupilumab, mepolizumab, benralizumab, tezepelumab, and MEDI8968). Dupilumab reduce exacerbation rates and improved lung function and quality of life in patients with type 2 inflammation. Mepolizumab showed modest benefit in eosinophilic COPD. Other treatments, including benralizumab and tezepelumab, failed to demonstrate consistent clinical efficacy.
Conclusion: Biologics treatment show a selective benefits in COPD patients with eosinophilic or T2-high inflammation, mainly with dupilumab. Further studies are needed to define optimal patient selection and assess long-term safety and cost-effectiveness.
Keywords: Chronic obstructive pulmonary disease; Biologic therapy; Eosinophilic inflammation; Dupilumab; Mepolizumab; Benralizumab; Tezepelumab
References
2. Pitre T, Lupas D, Mah J, Stanbrook M, Blazer A, Zeraatkar D, et al. Biologic Therapies for Chronic Obstructive Pulmonary Disease: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials. COPD J Chronic Obstr Pulm Dis. 2025 Jan 3;22(1). doi: 10.1080/15412555.2025.2449889
3. Mkorombindo T, Dransfield MT. Mepolizumab in the treatment of eosinophilic chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis. 2019 Aug;Volume 14:1779–87.
4. Donovan T, Milan SJ, Wang R, Banchoff E, Bradley P, Crossingham I. Anti-IL-5 therapies for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2020 Dec 8;2020(12). doi: 10.1002/14651858.CD013432.pub2
5. Narendra DK, Hanania NA. Targeting IL-5 in COPD. Int J Chron Obstruct Pulmon Dis. 2019 May;Volume 14:1045–51.
6. Freund O, Wand O, Kutzkel S, Tiran B, Pumin I, Friedman Regev I, et al. Real-World and Patient-Reported Outcomes of Dupilumab and Other Biological Drugs for Chronic Obstructive Pulmonary Disease—A Systematic Review. Diagnostics. 2024 Oct 26;14(21):2390.
7. Bolger GB. Therapeutic Targets and Precision Medicine in COPD: Inflammation, Ion Channels, Both, or Neither? Int J Mol Sci. 2023 Dec 11;24(24):17363.
8. Criner GJ, Celli BR, Brightling CE, Agusti A, Papi A, Singh D, et al. Benralizumab for the Prevention of COPD Exacerbations. N Engl J Med. 2019 Sep 12;381(11):1023–34. d10.1056/NEJMoa1905248
9. Pavord ID, Chanez P, Criner GJ, Kerstjens HAM, Korn S, Lugogo N, et al. Mepolizumab for Eosinophilic Chronic Obstructive Pulmonary Disease. N Engl J Med. 2017 Oct 26;377(17):1613–29. doi: 10.1056/NEJMoa1708208
10. Singh D, Brightling CE, Rabe KF, Han MK, Christenson SA, Drummond MB, et al. Efficacy and safety of tezepelumab versus placebo in adults with moderate to very severe chronic obstructive pulmonary disease (COURSE): a randomised, placebo-controlled, phase 2a trial. Lancet Respir Med. 2025 Jan;13(1):47–58.
11. Bhatt SP, Rabe KF, Hanania NA, Vogelmeier CF, Bafadhel M, Christenson SA, et al. Dupilumab for chronic obstructive pulmonary disease with type 2 inflammation: a pooled analysis of two phase 3, randomised, double-blind, placebo-controlled trials. Lancet Respir Med. 2025 Mar;13(3):234–43.
12. Brightling CE, Bleecker ER, Panettieri RA, Bafadhel M, She D, Ward CK, et al. Benralizumab for chronic obstructive pulmonary disease and sputum eosinophilia: a randomised, double-blind, placebo-controlled, phase 2a study. Lancet Respir Med. 2014 Nov;2(11):891–901.
13. Calverley PMA, Sethi S, Dawson M, Ward CK, Finch DK, Penney M, et al. A randomised, placebo-controlled trial of anti–interleukin-1 receptor 1 monoclonal antibody MEDI8968 in chronic obstructive pulmonary disease. Respir Res. 2017 Dec 9;18(1):153.
14. Bhatt SP, Rabe KF, Hanania NA, Vogelmeier CF, Cole J, Bafadhel M, et al. Dupilumab for COPD with Type 2 Inflammation Indicated by Eosinophil Counts. N Engl J Med. 2023 Jul 20;389(3):205–14. doi: 10.1056/NEJMoa2303951
15. Hu KC, Chuang MH, Lai CC, Liao KM. Meta-Analysis of Randomized, Controlled Trials Assessing the Effectiveness and Safety of Biological Treatments in Chronic Obstructive Pulmonary Disease Patients. Clin Ther. 2025 Mar;47(3):226–34.
16. Brightling CE, Saha S, Hollins F. Interleukin‐13: prospects for new treatments. Clin Exp Allergy. 2010 Jan 15;40(1):42–9. doi: 10.1111/j.1365-2222.2009.03383.x
17. Kersul AL, Cosio BG. Biologics in COPD. Open Respir Arch. 2024 Apr;6(2):100306.
18. Suresh V, Mih JD, George SC. Measurement of IL-13–Induced iNOS-Derived Gas Phase Nitric Oxide in Human Bronchial Epithelial Cells. Am J Respir Cell Mol Biol. 2007 Jul;37(1):97–104. doi: 10.1165/rcmb.2006-0419OC
19. Pelaia G, Vatrella A, Gallelli L, Renda T, Caputi M, Maselli R, et al. Biological targets for therapeutic interventions in COPD: clinical potential. Int J COPD. 2006 Aug;1(3):321–34. doi: 10.2147/copd.2006.1.3.321