Новые вопросы в фокусе применения биологической терапии при лечении полипозного риносинусита и Т2-ассоциированных воспалительных заболеваний

Будковая М.А., Реброва С.А., Рязанцев С.В., Дворянчиков В.В., Дахадаева П.М., Тырнова Е.В. Новые вопросы в фокусе применения биологической терапии при лечении полипозного риносинусита и Т2-ассоциированных воспалительных заболеваний. Consilium Medicum. 2025;27(9):538–542. DOI: 10.26442/20751753.2025.9.203350

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Budkovaia MA, Rebrova SA, Ryazantsev SV, Dvorianchikov VV, Dakhadaeva PM, Tyrnova EV. New issues in the focus of biological therapy in the treatment of rhinosinusitis with nasal polyps and T2-associated inflammatory diseases: A review. Consilium Medicum. 2025;27(9):538–542. DOI: 10.26442/20751753.2025.9.203350

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Аннотация

В настоящее время эозинофилы периферической крови рассматриваются в качестве важного маркера при определении ведущего эндотипа воспалительной реакции у пациентов с тяжелым неконтролируемым полипозным риносинуситом. При этом отмечаются выраженное превалирование Т2-эндотипа воспаления среди данной группы больных и частое сочетание с другими Т2-иммуноопосредованными заболеваниями. В соответствии с современной стратегией лечения тяжелого неконтролируемого полипозного риносинусита расчет абсолютного количества эозинофилов в крови является необходимым условием при принятии решения о назначении генно-инженерной биологической терапии. Однако наряду с высокой эффективностью данного лечения по результатам клинических исследований и в условиях реальной клинической практики некоторые авторы отмечают развитие преходящей эозинофилии в крови, вплоть до развития гиперэозинофильного синдрома у отдельных пациентов, получающих лечение дупилумабом. Данная ситуация требует детального мониторинга за изменением уровня эозинофилов в периферической крови в связи с возможными рисками токсического действия на эпителиальные клетки дыхательных путей, клетки сердечной мышцы и эндотелий сосудов.

Ключевые слова: эозинофилия, хронический полипозный риносинусит, дупилумаб, гиперэозинофильный синдром, биологическая терапия

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Peripheral blood eosinophils are now seen as an important marker in determining the leading endotype of the inflammatory response in patients with severe uncontrolled rhinosinusitis polyposa. The T2-endotype of inflammation is dominant in this group of patients, frequently associated with other T2-immunomediated diseases. In accordance with the current strategy for treating severe, uncontrolled rhinosinusitis polyposa, the absolute eosinophil count is a prerequisite for deciding on the use of genetically engineered biological therapy. However, despite the high efficacy of these treatments as demonstrated by the results of clinical studies and real-world clinical practice, transient blood eosinophilia has been reported, sometimes with the development of hypereosinophilic syndrome in individual patients receiving dupilumab treatment. This situation requires detailed monitoring of changes in the peripheral blood eosinophil count due to the potential risks of toxic effects on the epithelial cells of the respiratory tract, cardiac muscle cells, and vascular endothelium.

Keywords: eosinophilia, rhinosinusitis with nasal polyp, dupilumab, hypereosinophilic syndrome, biological therapy

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Список литературы

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11. Trautmann A, Akdis M, Kleemann D, et al. T cell-mediated Fas-induced keratinocyte apoptosis plays a key pathogenetic role in eczematous dermatitis. J Clin Invest. 2000;106(1):25-35. DOI:10.1172/JCI9199
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13. Koennecke M, Klimek L, Mullol J, et al. Subtyping of polyposis nasi: phenotypes, endotypes and comorbidities. Allergo J Int. 2018;27(2):56-65. DOI:10.1007/s40629-017-0048-5
14. Khan A, Gouia I, Kamat S, et al. Type 2 inflammation-related comorbidities among patients with asthma, chronic rhinosinusitis with nasal polyps, and atopic dermatitis. Eur Respir J. 2020;56:232. DOI:10.1183/13993003.congress-2020.23
15. Fokkens WJ, Viskens AS, Backer V, et al. EPOS/EUFOREA update on indication and evaluation of Biologics in Chronic Rhinosinusitis with Nasal Polyps 2023. Rhinology. 2023;61(3):194-202. DOI:10.4193/Rhin22.489
16. Будковая М.А., Рязанцев С.В., Дворянчиков В.В., и др. Перспективы применения биологической терапии при полипозном риносинусите и других Т2-ассоциированных иммуноопосредованных воспалительных заболеваниях. Эффективная фармакотерапия. 2021;17(18):16-20 [Budkovaya MA, Ryazantsev SV, Dvoryanchikov VV, et al. Prospects for the Use of Biological Therapy in Chronic Rhinosinusitis with Nasal Polyps and Other T2-Associated Immuno-Mediated Inflammatory Diseases. Effective Pharmacotherapy. 2021;17(18):16-20 (in Russian)]. DOI:10.33978/2307-3586-2021-17-18-16-20
17. Bachert C, Han JK, Desrosiers M, et al. Efficacy and safety of dupilumab in patients with severe chronic rhinosinusitis with nasal polyps (LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52): results from two multicentre, randomised, double-blind, placebo-controlled, parallel-group phase 3 trials. Lancet. 2019;394(10209):1638-60. DOI:10.1016/S0140-6736(19)31881-1
18. Jansen F, Becker B, Eden JK, et al. Dupilumab (Dupixent(®)) tends to be an effective therapy for uncontrolled severe chronic rhinosinusitis with nasal polyps: real data of a single-centered, retrospective single-arm longitudinal study from a university hospital in Germany. Eur Arch Otorhinolaryngol. 2023;280(4):1741-75. DOI:10.1007/s00405-022-07679-y
19. Wechsler ME, Klion AD, Paggiaro P, et al. Effect of Dupilumab on Blood Eosinophil Counts in Patients With Asthma, Chronic Rhinosinusitis With Nasal Polyps, Atopic Dermatitis, or Eosinophilic Esophagitis. J Allergy Clin Immunol Pract. 2022;10(10):2695-709. DOI:10.1016/j.jaip.2022.05.019
20. Rabe KF, Nair P, Brusselle G, et al. Efficacy and Safety of Dupilumab in Glucocorticoid-Dependent Severe Asthma. N Engl J Med. 2018;378(26):2475-85. DOI:10.1056/NEJMoa1804093
21. Zhou X, Yang G, Zeng X, et al. Dupilumab and the potential risk of eosinophilic pneumonia: case report, literature review, and FAERS database analysis. Front Immunol. 2023;14:1277734. DOI:10.3389/fimmu.2023.1277734
22. Реброва С.А., Будковая М.А., Рязанцев С.В. Гиперэозинофилия при лечении дупилумабом у пациентов с тяжелым неконтролируемым полипозным риносинуситом. Российская оториноларингология. 2025;24(1):21-9 [Rebrova SA, Budkovaya MA, Ryazantsev SV. Hypereosinophilia during dupilumab treatment in patients with severe uncontrolled chronic rhinosinusitis with nasal polyps. Russian Otorhinolaryngology. 2025;24(1):21-9 (in Russian)]. DOI:10.18692/1810-4800-2025-1-21-29
23. Nakashima D, Mori E, Otori N. A case of recurrent chronic eosinophilic pneumonia after switching from benralizumab to dupilumab. Respir Med Case Rep. 2024;47:101968. DOI:10.1016/j.rmcr.2023.101968
24. Eger K, Pet L, Weersink EJM, Bel EH. Complications of switching from anti-IL-5 or anti-IL-5R to dupilumab in corticosteroid-dependent severe asthma. J Allergy Clin Immunol Pract. 2021;9(7):2913-95. DOI:10.1016/j.jaip.2021.02.042
25. Nishiyama Y, Koya T, Nagano K, et al. Two cases of dupilumab-associated eosinophilic pneumonia in asthma with eosinophilic chronic rhinosinusitis: IL-5-driven pathology? Allergol Int. 2022;71(4):548-51. DOI:10.1016/j.alit.2022.03.005
26. Rogers L, Jesenak M, Bjermer L, et al. Biologics in severe asthma: A pragmatic approach for choosing the right treatment for the right patient. Respir Med. 2023;218:107414:S0954-6111(23)00302-5. DOI:10.1016/j.rmed.2023.107414
27. Kai M, Vion PA, Boussouar S, et al. Eosinophilic granulomatosis polyangiitis (EGPA) complicated with periaortitis, precipitating role of dupilumab? A case report a review of the literature. RMD Open. 2023;9(3):e003300. DOI:10.1136/rmdopen-2023-003300
28. Yamazaki K, Nomizo T, Hatanaka K, et al. Eosinophilic granulomatosis with polyangiitis after treatment with dupilumab. J Allergy Clin Immunol Glob. 2022;1(3):180-8. DOI:10.1016/j.jacig.2022.03.006
29. Blanchard C, Rothenberg ME. Biology of the eosinophil. Adv Immunol. 2009;101:81-121. DOI:10.1016/S0065-2776(08)01003-1
30. Прилуцкий А.С., Сорокина О.В., Прилуцкая О.А., Баранова О.В. Эозинофилы в норме и патологии. Структура, медиаторы, развитие. Аллергология и Иммунология в Педиатрии. 2023;(1):5-15 [Prilutskij AS, Sorokina OV, Prilutskaia OA, Baranova OV. Eosinophils in normal and pathological conditions. Structure, mediators, development. Allergology and Immunology in Paediatrics. 2023;(1):5-15 (in Russian)]. DOI:10.53529/2500-1175-2023-1-5-15
31. Tajima K, Katagiri T. Deposits of eosinophil granule proteins in eosinophilic cholecystitis and eosinophilic colitis associated with hypereosinophilic syndrome. Dig Dis Sci. 1996;41(2):282-8. DOI:10.1007/BF02093816
32. Slungaard A, Mahoney JR Jr. Bromide-dependent toxicity of eosinophil peroxidase for endothelium and isolated working rat hearts: a model for eosinophilic endocarditis. J Exp Med. 1991;173(1):117-26. DOI:10.1084/jem.173.1.117
33. Dispenza MC, Bochner BS. Diagnosis and Novel Approaches to the Treatment of Hypereosinophilic Syndromes. Curr Hematol Malig Rep. 2018;13(3):191-201. DOI:10.1007/s11899-018-0448-8

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1. Ryazantsev SV. Tactics of treatment of polypose rinosinusite. Rossiiskaya otorinolaringologiya. 2017;2(87):162-9 (in Russian). DOI:10.18692/1810-4800-2017-2-162-169
2. Budkovaia MA, Ryazantsev SV. Comprehensive assessment of the effectiveness and safety of conservative treatment of chronic rhinosinusitis. Russian Rhinology. 2020;28(3):125-31 (in Russian). DOI:10.17116/rosrino202028031125
3. Savlevich EL, Cherenkova VA, Molodnitskaia AY. Basic principles for the treatment of chronic rhinosinusitis with nasal polyps. Meditsinskiy sovet = Medical Council. 2020;(16):73-8 (in Russian). DOI:10.21518/2079-701x-2020-16-73-78
4. Pavlush DG, Gilifanov EA, Dyuizen IV, et al. Analysis of incidence of patients with polypous rhinosinusitis of different age groups in Primorsky Krai for period of 2015–2019. Rossiiskaya otorinolaringologiya. 2022;21(1):51-6 (in Russian). DOI:10.18692/1810-4800-2022-1-51-56
5. Mullol Dzh, Azar A, Bukhkhait KM, et al. Khronicheskii rinosinusit s polipami nosa: kachestvo zhizni v epokhu biologicheskikh preparatov. Klinika allergii. Immunologiia. Praktika. 2022;10(9):1434-53 (in Russian).
6. Stevens WW, Peters AT, Tan BK, et al. Associations Between Inflammatory Endotypes and Clinical Presentations in Chronic Rhinosinusitis. J Allergy Clin Immunol Pract. 2019;7(8):2812-2820.e3. DOI:10.1016/j.jaip.2019.05.009
7. Orlandi RR, Kingdom TT, Smith TL, et al. International consensus statement on allergy and rhinology: rhinosinusitis 2021. Int Forum Allergy Rhinol. 2021;11(3):213-739. DOI:10.1002/alr.22741
8. Staudacher AG, Peters AT, Kato A, Stevens WW. Use of endotypes, phenotypes, and inflammatory markers to guide treatment decisions in chronic rhinosinusitis. Ann Allergy Asthma Immunol. 2020;124(4):318-25. DOI:10.1016/j.anai.2020.01.013
9. Larin RA, Mokeeva PP, Grishin AS. Experience of biological therapy in severe forms of chronic rhinosinusitis with nasal polyps in the conditions of regional healthcare. Russian Bulletin of Otorhinolaryngology. 2023;88(2):51‑8 (in Russian). DOI:10.17116/otorino20228802151
10. Viksne RJ, Sumeraga G, Pilmane M. Endotypes of Chronic Rhinosinusitis with Primary and Recurring Nasal Polyps in the Latvian Population. Int J Mol Sci. 2024;25(10):5159. DOI:10.3390/ijms25105159
11. Trautmann A, Akdis M, Kleemann D, et al. T cell-mediated Fas-induced keratinocyte apoptosis plays a key pathogenetic role in eczematous dermatitis. J Clin Invest. 2000;106(1):25-35. DOI:10.1172/JCI9199
12. Trautmann A, Schmid-Grendelmeier P, Krüger K, et al. T cells and eosinophils cooperate in the induction of bronchial epithelial cell apoptosis in asthma. J Allergy Clin Immunol. 2002;109(2):329-37. DOI:10.1067/mai.2002.121460
13. Koennecke M, Klimek L, Mullol J, et al. Subtyping of polyposis nasi: phenotypes, endotypes and comorbidities. Allergo J Int. 2018;27(2):56-65. DOI:10.1007/s40629-017-0048-5
14. Khan A, Gouia I, Kamat S, et al. Type 2 inflammation-related comorbidities among patients with asthma, chronic rhinosinusitis with nasal polyps, and atopic dermatitis. Eur Respir J. 2020;56:232. DOI:10.1183/13993003.congress-2020.23
15. Fokkens WJ, Viskens AS, Backer V, et al. EPOS/EUFOREA update on indication and evaluation of Biologics in Chronic Rhinosinusitis with Nasal Polyps 2023. Rhinology. 2023;61(3):194-202. DOI:10.4193/Rhin22.489
16. Budkovaya MA, Ryazantsev SV, Dvoryanchikov VV, et al. Prospects for the Use of Biological Therapy in Chronic Rhinosinusitis with Nasal Polyps and Other T2-Associated Immuno-Mediated Inflammatory Diseases. Effective Pharmacotherapy. 2021;17(18):16-20 (in Russian). DOI:10.33978/2307-3586-2021-17-18-16-20
17. Bachert C, Han JK, Desrosiers M, et al. Efficacy and safety of dupilumab in patients with severe chronic rhinosinusitis with nasal polyps (LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52): results from two multicentre, randomised, double-blind, placebo-controlled, parallel-group phase 3 trials. Lancet. 2019;394(10209):1638-60. DOI:10.1016/S0140-6736(19)31881-1
18. Jansen F, Becker B, Eden JK, et al. Dupilumab (Dupixent(®)) tends to be an effective therapy for uncontrolled severe chronic rhinosinusitis with nasal polyps: real data of a single-centered, retrospective single-arm longitudinal study from a university hospital in Germany. Eur Arch Otorhinolaryngol. 2023;280(4):1741-75. DOI:10.1007/s00405-022-07679-y
19. Wechsler ME, Klion AD, Paggiaro P, et al. Effect of Dupilumab on Blood Eosinophil Counts in Patients With Asthma, Chronic Rhinosinusitis With Nasal Polyps, Atopic Dermatitis, or Eosinophilic Esophagitis. J Allergy Clin Immunol Pract. 2022;10(10):2695-709. DOI:10.1016/j.jaip.2022.05.019
20. Rabe KF, Nair P, Brusselle G, et al. Efficacy and Safety of Dupilumab in Glucocorticoid-Dependent Severe Asthma. N Engl J Med. 2018;378(26):2475-85. DOI:10.1056/NEJMoa1804093
21. Zhou X, Yang G, Zeng X, et al. Dupilumab and the potential risk of eosinophilic pneumonia: case report, literature review, and FAERS database analysis. Front Immunol. 2023;14:1277734. DOI:10.3389/fimmu.2023.1277734
22. Rebrova SA, Budkovaya MA, Ryazantsev SV. Hypereosinophilia during dupilumab treatment in patients with severe uncontrolled chronic rhinosinusitis with nasal polyps. Russian Otorhinolaryngology. 2025;24(1):21-9 (in Russian). DOI:10.18692/1810-4800-2025-1-21-29
23. Nakashima D, Mori E, Otori N. A case of recurrent chronic eosinophilic pneumonia after switching from benralizumab to dupilumab. Respir Med Case Rep. 2024;47:101968. DOI:10.1016/j.rmcr.2023.101968
24. Eger K, Pet L, Weersink EJM, Bel EH. Complications of switching from anti-IL-5 or anti-IL-5R to dupilumab in corticosteroid-dependent severe asthma. J Allergy Clin Immunol Pract. 2021;9(7):2913-95. DOI:10.1016/j.jaip.2021.02.042
25. Nishiyama Y, Koya T, Nagano K, et al. Two cases of dupilumab-associated eosinophilic pneumonia in asthma with eosinophilic chronic rhinosinusitis: IL-5-driven pathology? Allergol Int. 2022;71(4):548-51. DOI:10.1016/j.alit.2022.03.005
26. Rogers L, Jesenak M, Bjermer L, et al. Biologics in severe asthma: A pragmatic approach for choosing the right treatment for the right patient. Respir Med. 2023;218:107414:S0954-6111(23)00302-5. DOI:10.1016/j.rmed.2023.107414
27. Kai M, Vion PA, Boussouar S, et al. Eosinophilic granulomatosis polyangiitis (EGPA) complicated with periaortitis, precipitating role of dupilumab? A case report a review of the literature. RMD Open. 2023;9(3):e003300. DOI:10.1136/rmdopen-2023-003300
28. Yamazaki K, Nomizo T, Hatanaka K, et al. Eosinophilic granulomatosis with polyangiitis after treatment with dupilumab. J Allergy Clin Immunol Glob. 2022;1(3):180-8. DOI:10.1016/j.jacig.2022.03.006
29. Blanchard C, Rothenberg ME. Biology of the eosinophil. Adv Immunol. 2009;101:81-121. DOI:10.1016/S0065-2776(08)01003-1
30. Prilutskij AS, Sorokina OV, Prilutskaia OA, Baranova OV. Eosinophils in normal and pathological conditions. Structure, mediators, development. Allergology and Immunology in Paediatrics. 2023;(1):5-15 (in Russian). DOI:10.53529/2500-1175-2023-1-5-15
31. Tajima K, Katagiri T. Deposits of eosinophil granule proteins in eosinophilic cholecystitis and eosinophilic colitis associated with hypereosinophilic syndrome. Dig Dis Sci. 1996;41(2):282-8. DOI:10.1007/BF02093816
32. Slungaard A, Mahoney JR Jr. Bromide-dependent toxicity of eosinophil peroxidase for endothelium and isolated working rat hearts: a model for eosinophilic endocarditis. J Exp Med. 1991;173(1):117-26. DOI:10.1084/jem.173.1.117
33. Dispenza MC, Bochner BS. Diagnosis and Novel Approaches to the Treatment of Hypereosinophilic Syndromes. Curr Hematol Malig Rep. 2018;13(3):191-201. DOI:10.1007/s11899-018-0448-8

Авторы

М.А. Будковая*^1,2, С.А. Реброва¹, С.В. Рязанцев¹, В.В. Дворянчиков¹, П.М. Дахадаева¹, Е.В. Тырнова¹

¹ФГБУ «Санкт-Петербургский научно-исследовательский институт уха, горла, носа и речи» Минздрава России, Санкт-Петербург, Россия;
²ФГБОУ ВО «Санкт-Петербургский государственный университет», Санкт-Петербург, Россия
*marina-laptijova@yandex.ru

________________________________________________

Marina A. Budkovaia*^1,2, Svetlana A. Rebrova¹, Sergey V. Ryazantsev¹, Vladimir V. Dvorianchikov¹, Patimat M. Dakhadaeva¹, Elena V. Tyrnova¹

¹Saint Petersburg Research Institute of Ear, Throat, Nose and Speech, Saint Petersburg, Russia;
²Saint Petersburg State University, Saint Petersburg, Russia
*marina-laptijova@yandex.ru

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