Biological therapy of severe bronchial asthma

  • Received 04.04.2023

  • Revised 22.05.2023

  • Accepted 26.06.2023



  • 1,474 Views

  • Retrieved from Vol. 5, No. 2, 2023

  • Pages 86-92

Bronchial asthma is a major public health problem in the world. A considerable proportion of patients suffer from severe asthma, which is manifested by a decrease in the quality of life, an increase in the frequency of exacerbations, hospitalisations, and mortality. The ineffectiveness of conventional therapy in such patients contributes to the development of biological treatment methods with higher specificity, aimed at the pathogenetic links of the disease. The purpose of the study was to analyse the effectiveness of the treatment of severe bronchial asthma with monoclonal antibodies based on literature data. The study examines publications over the past 5 years that are available on the Internet. The following terms were used for the search: monoclonal antibodies, endotype, phenotype. Five monoclonal antibody biological agents targeting IgE, IL-5, IL-4, and IL-13, which are approved for use in patients with severe asthma, were analysed: omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab. The use of these medications has led to progress in the treatment of bronchial asthma. It was found that determining disease endotypes based on the assessment of biomarkers such as eosinophil count in blood and sputum, fractional exhaled nitric oxide, and serum periostin contributes to the greater effectiveness of biological therapy. It was investigated that monoclonal antibody treatment improves lung function, reduces exacerbation frequency, and decreases the need for additional medications. Many other biological agents, particularly those targeting key cytokines, are in the clinical development stage. Approved monoclonal antibodies targeting IgE, IL-5, and IL-4/IL13 demonstrate high efficacy in the treatment of severe bronchial asthma. The use of these agents in patients with severe asthma and high Th2 levels considerably improves lung function, symptom control, and reduces the frequency of disease exacerbations

biological agents; monoclonal antibodies; endotype; phenotype; biomarkers

https://doi.org/10.61751/bmbr.2706-6290.2023.2.86

[1] The Global Asthma Report. Int J Tuberc Lung Dis. 2022;26(Suppl 1):S1-S102. Available from: http://dx.doi.org/10.5588/ ijtld.22.1010

[2] Global Initiative for Asthma. Global strategy for asthma management and prevention. 2022. Available from: https:// ginasthma.org/wp-content/uploads/2022/07/GINA-Main-Report-2022-FINAL-22-07-01-WMS.pdf

[3] Settipane RA, Kreindler JL, Chung Y, Tkacz J. Evaluating direct costs and productivity losses of patients with asthma receiving GINA 4/5 therapy in the United States. Ann Allergy Asthma Immunol. 2019 Dec;123(6):564–72.e3. DOI: 10.1016/j.anai.2019.08.462

[4] Sulaiman I, Greene G, MacHale E, Seheult J, Mokoka M, D’Arcy S, et al. A randomised clinical trial of feedback on inhaler adherence and technique in patients with severe uncontrolled asthma. Eur Respir J. 2018 Jan 4;51(1):1701126. DOI: 10.1183/13993003.01126-2017

[5] Chung KF, Dixey P, Abubakar-Waziri H, Bhavsar P, Patel PH, Guo S, Ji Y. Characteristics, phenotypes, mechanisms and management of severe asthma. Chin Med J (Engl). 2022 May 20;135(10):1141–55. DOI: 10.1097/CM9.0000000000001990

[6] Volmer T, Effenberger T, Trautner C, Buhl R. Consequences of long-term oral corticosteroid therapy and its sideeffects in severe asthma in adults: A focused review of the impact data in the literature. Eur Respir J. 2018 Oct 25;52(4):1800703. DOI: 10.1183/13993003.00703-2018

[7] Price DB, Trudo F, Voorham J, Xu X, Kerkhof M, Ling Zhi Jie J, et al. Adverse outcomes from initiation of systemic corticosteroids for asthma: Long-term observational study. J Asthma Allergy. 2018 Aug 29;11:193–4. DOI: 10.2147/ JAA.S176026

[8] Cataldo D, Louis R, Michils A, Peché R, Pilette C, Schleich F, Ninane V, Hanon S. Severe asthma: Oral corticosteroid alternatives and the need for optimal referral pathways. J Asthma. 2021 Apr;58(4):448–58. DOI: 10.1080/02770903.2019.1705335

[9] Rask-Andersen A, Leander M, Sundbom F, Lampa E, Oudin A, Leynaert B, et al. Health-related quality of life as associated with asthma control, psychological status and insomnia. Ups J Med Sci. 2022;127. DOI: 10.48101/ujms. v127.8967

[10] Kavanagh J, Jackson DJ, Kent BD. Sleep and asthma. Curr Opin Pulm Med. 2018 Nov;24(6):569–73. DOI: 10.1097/ MCP.0000000000000526

[11] Abdo M, Waschki B, Kirsten AM, Trinkmann F, Biller H, Herzmann C, et al. Persistent uncontrolled asthma: Longterm impact on physical activity and body composition. Asthma Allergy. 2021 Mar 12;14:229–40. DOI: 10.2147/JAA. S299756

[12] Reddel HK, Bacharier LB, Bateman ED, Brightling CE, Brusselle GG, Buhl R, et al. Global initiative for asthma strategy 2021: Executive summary and rationale for key changes. Allergy Clin Immunol Pract. 2022 Jan;10(1S):1–18. DOI: 10.1016/j.jaip.2021.10.001

[13] Busse WW. Biological treatments for severe asthma: A major advance in asthma care. Allergol Int. 2019 Apr;68(2):158–66. DOI: 10.1016/j.alit.2019.01.004

[14] Yatsyshyn RI, Kaminsky VY, Malishok OV. Modern approaches to the treatment of autoimmune diseases. [in Ukrainian]. Clinical Immunology. Allergology. Infectology. 2013;(1):5-11. Available from: https://kiai.com.ua/ua/ archive/2013/1%2860%29/pages-5-11/suchasni-pidhodi-do-likuvannya-avtoimunnih-zahvoryuvan

[15] Katial RK, Bensch GW, Busse WW, Chipps BE, Denson JL, Gerber AN, et al. Changing paradigms in the treatment of severe asthma: The role of biologic therapies. J Allergy Clin Immunol Pract. 2017 Mar-Apr;5(2S):1–14. DOI: 10.1016/j. jaip.2016.11.029

[16] Wenzel SE. Severe adult asthmas: Integrating clinical features, biology and therapeutics to improve outcomes. Am J Respir Crit Care Med. 2021 Apr 1;203(7):809–21. DOI: 10.1164/rccm.202009-3631CI

[17] Kunc P, Fabry J, Lucanska M, Pecova R. Biomarkers of bronchial asthma. Physiol Res. 2020 Mar 27;69(Suppl 1):29–34. DOI: 10.33549/physiolres.934398

[18] Edwards MR, Strong K, Cameron A, Walton RP, Jackson DJ, Johnston SL. Viral infections in allergy and immunology: How allergic inflammation influences viral infections and illness. J Allergy Clin Immunol. 2017 Oct;140(4):909–20. DOI: 10.1016/j.jaci.2017.07.025

[19] Tay TR, Lee JWY, Hew M. Diagnosis of severe asthma. Med J Aust. 2018 Jul 16;209(S2):3–10. DOI: 10.5694/mja18.00125

[20] Jones TL, Neville DM, Chauhan AJ. Diagnosis and treatment of severe asthma: A phenotype-based approach. Clin Med (Lond). 2018 Apr 1;18(Suppl 2):36–40. DOI: 10.7861/clinmedicine.18-2-s36

[21] Akar-Ghibril N, Casale T, Custovic A, Phipatanakul W. Allergic endotypes and phenotypes of asthma. J Allergy Clin Immunol Pract. 2020 Feb;8(2):429–40. DOI: 10.1016/j.jaip.2019.11.008

[22] Turrin M, Rizzo M, Bonato M, Bazzan E, Cosio MG, Semenzato U, et al. Differences between early- and lateonset asthma: Role of comorbidities in symptom control. J Allergy Clin Immunol Pract. 2022 Dec;10(12):3196–3. DOI: 10.1016/j.jaip.2022.08.007

[23] Taniguchi M, Mitsui C, Hayashi H, Ono E, Kajiwara K, Mita H, et al. Aspirin-exacerbated respiratory disease (AERD): Current understanding of AERD Allergol Int. 2019 Jul;68(3):289–95. DOI: 10.1016/j.alit.2019.05.001

[24] Matucci A, Bormioli S, Nencini F, Maggi E, Vultaggio A. The emerging role of type 2 inflammation in asthma. Expert Rev Clin Immunol. 2021 Jan;17(1):63–71. DOI: 10.1080/1744666X.2020.1860755

[25] Hudey SN, Ledford DK, Cardet JC. Mechanisms of non-type 2 asthma. Curr Opin Immunol. 2020 Oct;66:123–28. DOI: 10.1016/j.coi.2020.10.002

[26] Pakkasela J, Ilmarinen P, Honkamäki J, Tuomisto LE, Andersén H, Piirilä P, et al. Age-specific incidence of allergic and non-allergic asthma. BMC Pulm Med. 2020 Jan 10;20(1):9. DOI: 10.1186/s12890-019-1040-2

[27] Peters U, Dixon AE, Forno E. Obesity and asthma. J Allergy Clin Immunol. 2018 Apr;141(4):1169–79. DOI: 10.1016/j. jaci.2018.02.004

[28] Guguen C, Launois C, Dormoy V, Dewolf M, Dumazet A, Dury S, et al. [Obesity and asthma: Mechanisms and therapeutic options]. [in French]. Rev Mal Respir. 2020 Feb;37(2):134–43. DOI: 10.1016/j.rmr.2019.03.015

[29] Dragonieri S, Carpagnano GE. Biological therapy for severe asthma. Asthma Res Pract. 2021 Aug 13;7(1):12. DOI: 10.1186/s40733-021-00078-w

[30] Loureiro CC, Amaral L, Ferreira JA, Lima R, Pardal C, Fernandes I, et al. Omalizumab for severe asthma: Beyond allergic asthma. Biomed Res Int. 2018;2018:3254094. Published online 2018 Sep 17. DOI: 10.1155/2018/3254094

[31] Rojo-Tolosa S, González-Gutiérrez MV, Sánchez-Martínez JA, Jiménez-Gálvez G, Pineda-Lancheros LE, Gálvez-Navas JM, et al. Impact of omalizumab in patients with severe uncontrolled asthma and possible predictive biomarkers of response: A real-life study. Pharmaceutics. 2023 Feb 4;15(2):523. DOI: 10.3390/pharmaceutics15020523

[32] Humbert M, Taillé C, Mala L, Le Gros V, Just J, Molimard M; STELLAIR investigators. Omalizumab effectiveness in patients with severe allergic asthma according to blood eosinophil count: The STELLAIR study. Eur Respir J. 2018 May 10;51(5):1702523. DOI: 10.1183/13993003.02523-2017

[33] Schoettler N, Strek ME. Recent advances in severe asthma: From phenotypes to personalized medicine. Chest. 2020 Mar;157(3):516–28. DOI: 10.1016/j.chest.2019.10.009

[34] Harvey ES, Langton D, Katelaris C, Stevens S, Farah CS, Gillman A, et al. Mepolizumab effectiveness and identification of super-responders in severe asthma. Eur Respir J. 2020 May 21;55(5):1902420. DOI: 10.1183/13993003.02420-2019

[35] Cooper K, Frampton G, Harris P, Rose M, Chorozoglou M, Pickett K. Reslizumab for treating asthma with elevated blood eosinophils inadequately controlled by inhaled corticosteroids: An evidence review group perspective of a NICE single technology appraisal. Pharmacoeconomics. 2018 May;36(5):545–53. DOI: 10.1007/s40273-017-0608-z

[36] Di Bona D, Crimi C, D’Uggento AM, Benfante A, Caiaffa MF, Calabrese C, et al. Effectiveness of benralizumab in severe eosinophilic asthma: Distinct sub-phenotypes of response identified by cluster analysis. Clin Exp Allergy. 2022 Feb;52(2):312–23. DOI: 10.1111/cea.14026

[37] Kurosawa M, Sutoh E. Severe uncontrolled eosinophilic asthma, which responded to benralizumab after failure to respond to mepolizumab. Ann Allergy Asthma Immunol. 2019 Apr;122(4):431–33. DOI: 10.1016/j.anai.2018.12.014

[38] Minami D, Kayatani H, Sato K, Fujiwara K, Shibayama T. Effectiveness of benralizumab for allergic and eosinophilic predominant asthma following negative initial results with omalizumab. Respir Case Rep. 2019;7(1):e00388. DOI: 10.1002/rcr2.388

[39] King GG, James A, Harkness L, Wark PAB. Pathophysiology of severe asthma: We’ve only just started. Respirology. 2018 Mar;23(3):262–71. DOI: 10.1111/resp.13251

[40] Corren J, Castro M, O’Riordan T, Hanania NA, Pavord ID, Quirce S, et al. Dupilumab efficacy in patients with uncontrolled, moderate-to-severe allergic asthma. J Allergy Clin Immunol Pract. 2020 Feb;8(2):516–26. DOI: 10.1016/j. jaip.2019.08.050

[41] Hoy SM. Dupilumab: A review in chronic rhinosinusitis with nasal polyps. Drugs. 2020 May;80(7):711–17. DOI: 10.1007/ s40265-020-01298-9

[42] Porsbjerg CM, Sverrild A, Lloyd CM, Menzies-Gow AN, Bel EH. Anti-alarmins in asthma: Targeting the airway epithelium with next-generation biologics. Eur Respir J. 2020 Nov 12;56(5):2000260. DOI: 10.1183/13993003.002602020

[43] Nolasco S, Pelaia C, Scioscia G, Campisi R, Crimi C. Tezepelumab for asthma. Drugs Today (Barc). 2022 Dec;58(12):591–3. DOI: 10.1358/dot.2022.58.12.3449205

[44] Menzies-Gow A, Corren J, Bourdin A, Chupp G, Israel E, Wechsler ME, et al. Tezepelumab in adults and adolescents with severe, uncontrolled asthma. N Engl J Med. 2021 May 13;384(19):1800–9. DOI: 10.1056/NEJMoa2034975

[45] Wechsler ME, Ruddy MK, Pavord ID, Israel E, Rabe KF, Ford LB, et al. Efficacy and safety of itepekimab in patients with moderate-to-severe asthma. N Engl J Med. 2021 Oct 28;385(18):1656–68. DOI: 10.1056/NEJMoa2024257

[46] Nair P, Prabhavalkar KS. Neutrophilic asthma and potentially related target therapies. Curr Drug Targets. 2020;21(4):374–88. DOI: 10.2174/1389450120666191011162526

[47] Mahar PD, Zubrinich CM, Manuelpillai N, Foley P. Combination treatment with monoclonal antibodies: Secukinumab, benralizumab, and dupilumab for the combined management of psoriasis and severe asthma. Australas J Dermatol. 2021 Aug 9; 62(4): 506–8. DOI: 10.1111/ajd.13676

[48] Nirula A, Nilsen J, Klekotka P, Kricorian G, Erondu N, Towne JE, et al. Effect of IL-17 receptor A blockade with brodalumab in inflammatory diseases. Rheumatology (Oxford). 2016 Dec;55(suppl 2):43–55. DOI: 10.1093/ rheumatology/kew346