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Targeted therapy for severe bronchial asthma: Phenotyping of patients and algorithm for selecting a genetically engineered biological drug

https://doi.org/10.21518/ms2024-518

Abstract

Introduction. The “spot” effect of immunobiological drugs necessitates patients' selection based on pathogenetic mechanisms of the disease to ensure therapy effectiveness.

Aim. To determine characteristics of T2-asthma main phenotypes and develop an algorithm for selecting a first- and second-line biologics.

Materials and methods. Being retrospective and prospective in nature the research was directed at adult patients with severe asthma who received target therapy and were included in the registry of Sverdlovsk region. Cluster analysis made it possible to identify the most distinctive features of allergic, nonallergic eosinophilic and mixed SA. Pathogenetic mechanisms of T2 inflammation determined the choice of first-and-second-line biologics.

Results. Allergic phenotype is characterized by existence of allergy and first appearance of asthma before the age of 18, satellite allergic rhinitis and the Phadiatop test result ≥ 1,53 PAU/L. The features of non-allergic eosinophilic asthma are as follows: asthma first appearance at the age of 32 and older, eosinophilia ≥ 150 cells/gl, absence of allergy, satellite chronic rhinosinusitis polyposa (CRSP) and NSAIDs intolerance. The features of the mixed asthma are as follows: first appearance at the age of ≥ 18 and < 32 years old, allergy in combination with eosinophilia ≥ 300 cells/gl, AR and a positive Phadiatop allergy test result, CRSP and NSAIDs intolerance. It is the allergic phenotype of SA when preference should be given to anti-IgE drug. Dealing with non-allergic phenotype of SA one should consider anti-IL5 biologics more preferable. Taking into consideration Th2 and ILC2 ways in action mechanism it is possible to affirm that anti-IL4R therapy is effective in mixed asthma.

Conclusions. In real clinical practice the initial phenotyping of SA facilitates the correct choice of a first- and second-line targeted drug.

About the Authors

V. V. Naumova
Urals State Medical University
Russian Federation

Veronika V. Naumova - Cand. Sci. (Med.), Assistant Professor of the Department of Faculty Therapy, Endocrinology, Allergology and Immunology, Urals State Medical University.

3, Repin St., Ekaterinburg, 620028



K. A. Zykov
Research Institute for Pulmonology of the Federal Medical Biological Agency; Russian University of Medicine (ROSUNIMED)
Russian Federation

Kirill А. Zykov - Corr. Member RAS, Dr. Sc. (Med.), Professor RAS, Deputy Director for Scientific and Innovative Work, Research Institute for Pulmonology of the Federal Medical Biological Agency; Head of the Department of Faculty Therapy and Occupational Diseases, A Russian University of Medicine (ROSUNIMED).

8, Orekhovy Boulevard, Moscow, 115682; 20, Bldg. 1, Delegatskaya St., Moscow, 127473



R. Valenta
Medical University of Vienna
Austria

Rudolf Valenta - Foreign Member RAS, Professor of Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna.

23, Spitalgasse St., Vienna, 1090



O. P. Kovtun
Urals State Medical University
Russian Federation

Olga P. Kovtun - Acad. RAS, Dr. Sci. (Med.), Professor, Rector Urals State Medical University.

3, Repin St., Ekaterinburg, 620028



E. K. Beltyukov
Urals State Medical University
Russian Federation

Evgeny K. Beltyukov - Corr. Member RAS, Dr. Sci. (Med.), Professor, Professor of the Department of Faculty Therapy, Endocrinology, Allergology and Immunology, Urals State Medical University.

3, Repin St., Ekaterinburg, 620028



О. S. Smolenskaya
Urals State Medical University
Russian Federation

Оlga G. Smolenskaya - Dr. Sci. (Med.), Professor; Head of the Department of Faculty Therapy, Endocrinology, Allergology and Immunology, Urals State Medical University.

3, Repin St., Ekaterinburg, 620028



G. A. Bykova
Urals State Medical University
Russian Federation

Galina A. Bykova - Cand. Sci. (Med.), Assistant of the Department of Faculty Therapy, Endocrinology, Allergology and Immunology, Urals State Medical University.

3, Repin St., Ekaterinburg, 620028



A. A. Shtanova
Federal Bureau of Medical and Social Expertise
Russian Federation

Aleksandra A. Shtanova - Resident, Federal Bureau of Medical and Social Expertise.

3, Ivan Susanin St., Moscow, 127486



References

1. Newby C, Heaney LG, Menzies-Gow A, Niven RM, Mansur A, Bucknall C et al. Statistical cluster analysis of the British Thoracic Society Severe refractory Asthma Registry: clinical outcomes and phenotype stability. PLoS ONE. 2014;9(7):e102987. https://doi.org/10.1371/journal.pone.0102987.

2. Denton E, Price DB, Tran TN, Canonica GW, Menzies-Gow A, FitzGerald JM et al. Cluster Analysis of Inflammatory Biomarker Expression in the International Severe Asthma Registry. J Allergy Clin Immunol Pract. 2021;9(7):2680-2688.e7. https://doi.org/10.1016/j.jaip.2021.02.059.

3. Bourdin A, Molinari N, Vachier I, Varrin M, Marin G, Gamez AS, Paganin F, Chanez P. Prognostic value of cluster analysis of severe asthma phenotypes. J Allergy Clin Immunol. 2014;134(5):1043-1050. https://doi.org/10.1016/j.jaci.2014.04.038.

4. Haldar P, Pavord ID, Shaw DE, Berry MA, Thomas M, Brightling CE et al. Cluster analysis and clinical asthma phenotypes. Am J Respir Crit Care Med. 2008;178(3):218-224. https://doi.org/10.1164/rccm.200711-1754OC.

5. Schatz M, Hsu JW, Zeiger RS, Chen W, Dorenbaum A, Chipps BE, Haselkorn T. Phenotypes determined by cluster analysis in severe or difficult-to-treat asthma. J Allergy Clin Immunol. 2014;133(6):1549-1556. https://doi.org/10.1016/j.jaci.2013.10.006.

6. Moore WC, Meyers DA, Wenzel SE, Teague WG, Li H, Li X et al. Identification of asthma phenotypes using cluster analysis in the Severe Asthma Research Program. Am J Respir Crit Care Med. 2010;181(4):315-323. https://doi.org/10.1164/rccm.200906-0896oc.

7. Rupani H, Murphy A, Bluer K, Renwick C, McQuitty P, Jackson DJ et al. Biologics in severe asthma: Which one, When and Where? Clin Exp Allergy. 2021;51(9):1225-1228. https://doi.org/10.1111/cea.13989.

8. Nagase H, Suzukawa M, Oishi K, Matsunaga K. Biologics for severe asthma: The real-world evidence, effectiveness of switching, and prediction factors for the efficacy. Allergol Int. 2023;72(1):11-23. https://doi.org/10.1016/j.alit.2022.11.008.

9. Ito A, Miyoshi S, Toyota H, Suzuki Y, Uehara Y, Hattori S et al. The overlapping eligibility for biologics in patients with severe asthma and phenotypes. Arerugi. 2022;71(3):210-220. https://doi.org/10.15036/arerugi.71.210.

10. Albers FC, Mullerova H, Gunsoy NB, Shin JY, Nelsen LM, Bradford ES et al. Biologic treatment eligibility for real-world patients with severe asthma: The IDEAL study. J Asthma. 2018;55(2):152-160. https://doi.org/10.1080/02770903.2017.1322611.

11. Naumova VV, Beltyukov EK, Kovtun OP, Smolenskaya OG, Bykova GA, Klyachina ES. Clinical and allergological characteristics of patients with severe bronchial asthma in the regional registry and phenotyping principles for the targeted therapy choice. Meditsinskiy Sovet. 2024;18(9):47-61. (In Russ.) https://doi.org/10.21518/ms2024-177.

12. Naumova V, Beltyukov E, Niespodziana K, Errhalt P, Valenta R, Karaulov A, Kiseleva D. Cumulative IgE-levels specific for respiratory allergens as biomarker to predict efficacy of anti-IgE-based treatment of severe asthma. Front Immunol. 2022;13:941492. https://doi.org/10.3389/fimmu.2022.941492.

13. Наумова ВВ, Бельтюков ЕК, Киселева ДВ. Способ диагностики аллергической тяжелой бронхиальной астмы. Патент RU 2786010 C1, 15.12.2022. Режим доступа: https://www.elibrary.ru/gvjhyd.

14. Naumova VV, Beltyukov ЕК, Kovtun OP, Bykova GA, Troshina VI, Mineeva AN. Direct comparative study of anti-IgE and anti-IL4Ra therapy effectiveness in patients with severe allergic and mixed bronchial asthma. Meditsinskiy Sovet. 2024;18(9):74-86. (In Russ.) https//doi.org/10.21518/ms2024-195.

15. Naumova VV, Beltyukov ЕК, Kovtun OP, Bykova GA, Smolenskaya OG, Shtanova AA, Stepina DA. Direct comparative study of the effectiveness of mepolizumab and dupilumab in patients with severe non-allergic eosinophilic asthma. Meditsinskiy Sovet. 2023;17(20):16-25. (In Russ.) https://doi.org/10.21518/ms2023-308.

16. Наумова ВВ, Бельтюков ЕК, Киселева ДВ. Схема «Фенотипы Т2 тяжелой бронхиальной астмы и персонализированный выбор генно-инженерной биологической терапии / препарата (Анти-IgE или анти-IL4R,13 или анти-IL5). Патент RU 141001, 14.03.2024. Режим доступа: https://www.fips.ru/registers-doc-view/fips_servlet?DB=RUDE&DocNumber=141001&TypeFile=html.

17. Naumova VV, Beltyukov EK, Kiseleva DV, Bykova GA, Smolenskaya OG, Shtanova AA, Stepina DA. Targeted therapy for severe asthma: switching biological agents in real clinical practice - causes, and consequences. Russian Journal of Allergy. 2023;20(4):439-454. https://doi.org/10.36691/RJA15993.

18. Kaur R, Chupp G. Phenotypes and endotypes of adult asthma: Moving toward precision medicine. J Allergy Clin Immunol. 2019;144(1):1-12. https://doi.org/10.1016/j.jaci.2019.05.031.

19. Heaney LG, Perez de Llano L, Al-Ahmad M, Backer V, Busby J, Canonica GW et al. Eosinophilic and Noneosinophilic Asthma: An Expert Consensus Framework to Characterize Phenotypes in a Global Real-Life Severe Asthma Cohort. Chest. 2021;160(3):814-830. https://doi.org/10.1016/j.chest.2021.04.013.

20. Baan EJ, de Roos EW, Engelkes M, de Ridder M, Pedersen L, Berencsi K et al. Characterization of Asthma by Age of Onset: A Multi-Database Cohort Study. J Allergy Clin Immunol Pract. 2022;10(7):1825-1834.e8. https://doi.org/10.1016/j.jaip.2022.03.019.

21. Quirce S, Heffler E, Nenasheva N, Demoly P, Menzies-Gow A, Moreira-Jorge A et al. Revisiting Late-Onset Asthma: Clinical Characteristics and Association with Allergy. J Asthma Allergy. 2020;13:743-752. https://doi.org/10.2147/JAA.S282205.

22. Tschopp JM, Sistek D, Schindler C, Leuenberger C, Perruchoud P, Wuthrich AP et al. Current allergic asthma and rhinitis : diagnostic efficiency of three commonly used atopic markers (IgE, skin prick tests, and Phadiatop). Results from 8329 randomized adults from the SAPALDIA study. Swiss study on air pollution and lung diseases in adults. Allergy. 1998;53(6):608-613. https://doi.org/10.1111/j.1398-9995.1998.tb03937.x.

23. Wever AM, Wever-Hess J, van Schayck CP, van Weel C. Evaluation of the Phadiatop test in an epidemiological study. Allergy. 1990;45(2):92-97. https://doi.org/10.1111/j.1398-9995.1990.tb00464.x.

24. Chang YC, Lee TJ, Huang CC, Chang PH, Chen YW, Fu CH. The Role of Phadiatop Tests and Total Immunoglobulin E Levels in Screening Aeroallergens: A Hospital-Based Cohort Study. J Asthma Allergy. 2021;14:135-140. https://doi.org/10.2147/JAA.S292710.

25. Wise SK, Lin SY, Toskala E. International Consensus Statement on Allergy and Rhinology: Allergic rhinitis-executive summury. Int Forum Allergy Rhinol. 2018;8(2):85-107. https://doi.org/10.1002/alr.22070.

26. Fokkens WJ, Lund VJ, Hopkins C, Hellings PW, Kern R, Reitsma S et al. European Position Paper on Rhinosinusitis and Nasal Polyps 2020. Rhinology. 2020;58(Suppl. 29):1-464. https://doi.org/10.4193/Rhin20.600.

27. Lotvall J, Akdis CA, Bacharier LB, Bjermer L, Casale TB, Custovic A et al. Asthma endotypes: a new approach to classification of disease entities within the asthma syndrome. J Allergy Clin Immunol. 2011;127(2):355-360. https://doi.org/10.1016/j.jaci.2010.11.037.

28. Agache I, Akdis C, Jutel M, Virchow JC. Untangling asthma phenotypes and endotypes. Allergy. 2012;67(7):835-846. https://doi.org/10.1111/j.1398-9995.2012.02832.x.

29. Chen W, Sadatsafavi M, Tran TN, Murray RB, Wong CBN, Ali N et al. Chara-cterization of Patients in the International Severe Asthma Registry with High Steroid Exposure Who Did or Did Not Initiate Biologic Therapy. J Asthma Allergy. 2022;15:1491-1510. https://doi.org/10.2147/JAA.S377174.

30. Miljkovic D, Bassiouni A, Cooksley C, Ou J, Hauben E, Wormald PJ, Vreugde S. Association between group 2 innate lymphoid cells enrichment, nasal polyps and allergy in chronic rhinosinusitis. Allergy. 2014;69(9):1154-1161. https://doi.org/10.1111/all.12440.

31. Nenasheva NM, Kurbacheva OM, Avdeev SN, Fedosenko S, Emel'yanov AV, Belevskiy AS et al. Practical recommendations for choosing an immunobiological preparation for the treatment of severe bronchial asthma of T2-endotype. Pulmonologiya. 2020;30(2):227-244. (In Russ.) https://doi.org/10.18093/0869-0189-2020-30-2-227-244.


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For citations:


Naumova VV, Zykov KA, Valenta R, Kovtun OP, Beltyukov EK, Smolenskaya ОS, Bykova GA, Shtanova AA. Targeted therapy for severe bronchial asthma: Phenotyping of patients and algorithm for selecting a genetically engineered biological drug. Meditsinskiy sovet = Medical Council. 2024;(20):82-91. (In Russ.) https://doi.org/10.21518/ms2024-518

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