adairАллергология и Иммунология в ПедиатрииAllergology and Immunology in Paediatrics2500-11752712-7958Ассоциация детских аллергологов и иммунологов России10.53529/2500-1175-2022-3-14-23adair-76Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESОпыт применения дупилумаба у пациентов с тяжелым атопическим дерматитомExperience with dupilumab in patients with atopic dermatitishttps://orcid.org/0000-0002-3004-6646ГлуховаE. A.GlukhovaE. A.

Евгения Александровна Глухова, врач-дерматовенеролог

отделение аллергологии и диетотерапии клиники

109240

Устьинский проезд, д. 2/14

125373

ул. Героев Панфиловцев, д. 28

119991

ул. Трубецкая, д. 8/2

Москва

Evgeniia Aleksandrovna Glukhova, dermatovenereologist

Department of Allergology and Diet Therapy of the Clinic 

109240

2/14, Ustyinsky proezd

125373

28, st. Geroev Panfilovtsev

119991

8/2, st. Trubetskaya

Moscow

evgeniya.shmeleva1994@yandex.ruhttps://orcid.org/0000-0003-3650-6305КувшиноваЕ. Д.KuvshinovaE. D.

Елена Дмитриевна Кувшинова, кандидат медицинских наук, старший научный сотрудник, врач-аллерголог

отделение аллергологии и диетотерапии клиники

109240

Устьинский проезд, д. 2/14

Москва

Elena Dmitrievna Kuvshinova, Candidate of Medical Sciences, Senior Researcher, Allergist

Department of Allergology and Diet Therapy of the Clinic

109240

2/14, Ustyinsky proezd

Moscow

len.kuwshinowa@yandex.ruhttps://orcid.org/0000-0002-1149-7927РевякинаВ. А.RevyakinaV. A.

Вера Афанасьевна Ревякина, доктор медицинских наук, профессор, заведующий отделением

отделение аллергологии и диетотерапии

109240

Устьинский проезд, д. 2/14

Москва

Vera Afanas’evna Revyakina, Doctor of Medical Sciences, professor, Head of the Department

Department of Allergology and Diet Therapy of theClinic

109240

2/14, Ustyinsky proezd

Moscow

5356797@mail.ruФедеральное государственное бюджетное учреждение науки «ФИЦ питания и биотехнологии»; Государственное бюджетное учреждение здравоохранения «Детская городская клиническая больница им. З. А. Башляевой» Департамента здравоохранения г. Москвы; Федеральное государственное автономное образовательное учреждение высшего образования «Первый Московский государственный медицинский университет имени И. М. Сеченова» Министерства здравоохранения Российской Федерации (Сеченовский университет)Federal Research Center of Nutrition and Biotechnology; Children’s City Clinical Hospital named after Z. A. Bashlyaeva of the Moscow Department of Health; I. M. Sechenov First Moscow State Medical University of Ministry of Healthcare of the Russian Federation (Sechenov University)Федеральное государственное бюджетное учреждение науки «ФИЦ питания и биотехнологии»Federal Research Center of Nutrition and Biotechnology202230072023031423Copyright © Глухова E.A., Кувшинова Е.Д., Ревякина В.А., 20232023Глухова E.A., Кувшинова Е.Д., Ревякина В.А.Glukhova E.A., Kuvshinova E.D., Revyakina V.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://adair.elpub.ru/jour/article/view/76

   По последним данным, ключевыми молекулами патогенеза атопического дерматита являются цитокины ИЛ-4 и ИЛ-13, которые инициируют и поддерживают Th2-воспаление. Таргетная терапия препаратом дупилумаб ингибирует сигнальную функцию этих цитокинов путем связывания субъединицы IL-4Rα, являющейся частью рецепторных комплексов ИЛ-4 и ИЛ-13. Препарат разрешен для лечения пациентов в возрасте старше 6 лет со среднетяжелым и тяжелым течением атопического дерматита. Эффективность и безопасность дупилумаба подтверждены результатами клинических исследований.

   Материал и методы

   Материал и методы. Под постоянным наблюдением находилось 27 детей с тяжелым течением атопического дерматита в возрасте 8–18 лет. Все пациенты получали системное лечение препаратом дупилумаб, наружно использовали топические глюкокортикостероиды (по необходимости), эмоленты (два раза в день). Дозирование дупилумаба производилось согласно инструкции к препарату.

   Результаты исследования. Спустя 26 недель комплексной терапии у 96,3 % пациентов было достигнуто значение индекса IGA = 0/1 и улучшение на 75 % по индексу EASI-75. Индекс SCORAD снизился со среднего значения 78,8 баллов до 13,7. Среднее значение общего IgE через 6 месяцев снизилось на 1518 кЕ/л. У 2 (7,4 %) пациентов отмечался конъюнктивит, который не являлся основанием для отмены препарата.

   Выводы

   Выводы. На фоне лечения дупилумабом наблюдается значительное снижение выраженности основных клинических симптомов атопического дерматита, в том числе зуда, нарушения сна.

   According to recent data, the key molecules in the pathogenesis of atopic dermatitis are the cytokines IL-4 and IL-13, which initiate and maintain Th2 inflammation. Targeted therapy with dupilumab inhibits the signaling function of these cytokines by binding to the IL-4Rα subunit, which is part of the IL-4 and IL-13 receptor complexes. The drug is approved for the treatment of patients over 6 years of age with moderate to severe AD. The efficacy and safety of dupilumab have been confirmed by the results of clinical studies.   Materials and methods. 27 children with severe AD at the age of 8–18 years were under constant supervision. All patients received systemic treatment with dupilumab, topically used topical glucocorticosteroids (if necessary), emollients (twice a day). Dosing of dupilumab was carried out according to the instructions for the drug.   Results. After 26 weeks of complex therapy, 96,3 % of patients achieved an IGA index value of 0/1 and an improvement of 75 % according to the EASI-75 index. The SCORAD index dropped from an average of 78,8 points to 13,7. The average value of total IgE after 6 months decreased by 1518 kU/l. In 2 (7,4 %) patients, conjunctivitis was noted, which was not a reason to discontinue the drug.   Conclusion. During treatment with dupilumab, there is a significant decrease in the severity of the main symptoms of atopic dermatitis, including itching, exacerbations.

атопический дерматитдупилумабSCORADEASIIGAatopic dermatitisdupilumabSCORADEASIIGAИсточник финансирования отсутствуетThere is no source of fundingReferencesKim BE, Leung DYM. Significance of Skin Barrier Dysfunction in Atopic Dermatitis. Allergy Asthma Immunol Res. 2018; 10 (3): 207–215. doi: 10.4168/aair.2018.10.3.207.Kim BE, Leung DYM. Significance of Skin Barrier Dysfunction in Atopic Dermatitis. Allergy Asthma Immunol Res. 2018; 10 (3): 207–215. doi: 10.4168/aair.2018.10.3.207.Garg N, Silverberg JI. Epidemiology of childhood atopic dermatitis. Clin Dermatol. 2015 May-Jun; 33 (3): 281–288. doi: 10.1016/j.clindermatol.2014.12.004. Epub 2014 Dec 8. PMID: 25889128.Garg N, Silverberg JI. Epidemiology of childhood atopic dermatitis. Clin Dermatol. 2015 May-Jun; 33 (3): 281–288. doi: 10.1016/j.clindermatol.2014.12.004. Epub 2014 Dec 8. PMID: 25889128.Sacotte R, Silverberg JI. Epidemiology of adult atopic dermatitis. Clin Dermatol. 2018 Sep-Oct; 36 (5): 595–605. doi: 10.1016/j.clindermatol.2018.05.007.Sacotte R, Silverberg JI. Epidemiology of adult atopic dermatitis. Clin Dermatol. 2018 Sep-Oct; 36 (5): 595–605. doi: 10.1016/j.clindermatol.2018.05.007.Nutten S. Atopic dermatitis: global epidemiology and risk factors. Ann Nutr Metab. 2015; 66 Suppl 1: 8–16. doi: 10.1159/000370220.Nutten S. Atopic dermatitis: global epidemiology and risk factors. Ann Nutr Metab. 2015; 66 Suppl 1: 8–16. doi: 10.1159/000370220.Dharmage SC, Lowe AJ, Matheson MC, Burgess JA, Allen KJ, Abramson MJ. Atopic dermatitis and the atopic march revisited. Allergy 2014; 69: 17–27.Dharmage SC, Lowe AJ, Matheson MC, Burgess JA, Allen KJ, Abramson MJ. Atopic dermatitis and the atopic march revisited. Allergy 2014; 69: 17–27.Drucker AM. Atopic dermatitis: Burden of illness, quality of life, and associated complications. Allergy Asthma Proc. 2017; 38 (1): 3–8.Drucker AM. Atopic dermatitis: Burden of illness, quality of life, and associated complications. Allergy Asthma Proc. 2017; 38 (1): 3–8.Brunner PM, Guttman-Yassky E, Leung DY. The immunology of atopic dermatitis and its reversibility with broad-spectrum and targeted therapies. J Allergy Clin Immunol. 2017; 139 (4S): S65–S76. doi: 10.1016/j.jaci.2017.01.011.Brunner PM, Guttman-Yassky E, Leung DY. The immunology of atopic dermatitis and its reversibility with broad-spectrum and targeted therapies. J Allergy Clin Immunol. 2017; 139 (4S): S65–S76. doi: 10.1016/j.jaci.2017.01.011.Атопический дерматит. Федеральные клинические рекомендации. Москва, 2021. — 84 с.Federal clinical guidelines for the management of patients with atopic dermatitis. 2021. — 81 p. (in Russ.)Thaçi D, Simpson EL, Beck LA et al. Efficacy and safety of dupilumab in adults with moderate-to-severe atopic dermatitis inade-quately controlled by topical treatments: a randomised, placebo-controlled, dose-ranging phase 2b trial. Lancet. 2016 Jan 2; 387 (10013): 40–52. doi: 10.1016/S0140-6736(15)00388-8.Thaçi D, Simpson EL, Beck LA et al. Efficacy and safety of dupilumab in adults with moderate-to-severe atopic dermatitis inade-quately controlled by topical treatments: a randomised, placebo-controlled, dose-ranging phase 2b trial. Lancet. 2016 Jan 2; 387 (10013): 40–52. doi: 10.1016/S0140-6736(15)00388-8.Kim J, Kim BE, Leung DYM. Pathophysiology of atopic dermatitis: Clinical implications. Allergy Asthma Proc. 2019; 40 (2): 84–92. doi: 10.2500/aap.2019.40.4202.Kim J, Kim BE, Leung DYM. Pathophysiology of atopic dermatitis: Clinical implications. Allergy Asthma Proc. 2019; 40 (2): 84–92. doi: 10.2500/aap.2019.40.4202.Silverberg J. Revolution of atopic dermatitis. J Allergy and Clinical Immunology. On practice. 2019; 140 (3): 2001 р.Silverberg J. Revolution of atopic dermatitis. J Allergy and Clinical Immunology. On practice. 2019; 140 (3): 2001 р.Brown SJ, Elias M, Bradley M. Genetics in Atopic Dermatitis: Historical Perspective and Future Prospects. J Actadermato-venerologica. 2020; 100 (12): 119 р.Brown SJ, Elias M, Bradley M. Genetics in Atopic Dermatitis: Historical Perspective and Future Prospects. J Actadermato-venerologica. 2020; 100 (12): 119 р.Loset M, Brown SJ, Saunes M, Hveem K. Genetics of Atopic Dermatitis: From DNA Sequence to Clinical Relevance. Dermatology. 2019; 235 (5): 355–364. doi: 10.1159/000500402.Loset M, Brown SJ, Saunes M, Hveem K. Genetics of Atopic Dermatitis: From DNA Sequence to Clinical Relevance. Dermatology. 2019; 235 (5): 355–364. doi: 10.1159/000500402.Lowenthal JW, Castle BE, Christiansen J et al. Expression of high affinity receptors for murine interleukin 4 (BSF-1) on hemopoietic and nonhemopoietic cells. J Immunol. 1988 Jan 15; 140 (2): 456–464.Lowenthal JW, Castle BE, Christiansen J et al. Expression of high affinity receptors for murine interleukin 4 (BSF-1) on hemopoietic and nonhemopoietic cells. J Immunol. 1988 Jan 15; 140 (2): 456–464.Morrison BE, Marcondes MC, Nomura DK et al. Cutting edge: IL-13Rα1 expression in dopaminergic neurons contributes to their oxidative stress-mediated loss following chronic peripheral treatment with lipopolysaccharide. J Immunol. 2012 Dec 15; 189 (12): 498–502. doi: 10.4049/jimmunol.1102150.Morrison BE, Marcondes MC, Nomura DK et al. Cutting edge: IL-13Rα1 expression in dopaminergic neurons contributes to their oxidative stress-mediated loss following chronic peripheral treatment with lipopolysaccharide. J Immunol. 2012 Dec 15; 189 (12): 498–502. doi: 10.4049/jimmunol.1102150.Zhu J. T-helper 2 (Th2) cell differentiation, type 2 innate lymphoid cell (ILC2) development and regulation of interleukin-4 (IL-4) and IL-13 production. Cytokine. 2015; 75 (1): 14–24. doi: 10.1016/j.cyto.2015.05.010.Zhu J. T-helper 2 (Th2) cell differentiation, type 2 innate lymphoid cell (ILC2) development and regulation of interleukin-4 (IL-4) and IL-13 production. Cytokine. 2015; 75 (1): 14–24. doi: 10.1016/j.cyto.2015.05.010.Otsuka A, Kabashima K. Mast cells and basophils in cutaneous immune responses. Allergy. 2015; 70 (2): 131–140. doi: 10.1111/all.12526.Otsuka A, Kabashima K. Mast cells and basophils in cutaneous immune responses. Allergy. 2015; 70 (2): 131–140. doi: 10.1111/all.12526.Akdis CA, Arkwright PD, Bruggen MC et al. Type 2 immunity in the skin and lungs. Allergy. 2020 Jul; 75 (7): 1582–1605. doi: 10.1111/all.14318.Akdis CA, Arkwright PD, Bruggen MC et al. Type 2 immunity in the skin and lungs. Allergy. 2020 Jul; 75 (7): 1582–1605. doi: 10.1111/all.14318.Steinhoff M, Buddenkotte J, Lerner EA. Role of mast cells and basophils in pruritus. Immunol Rev. 2018; 282 (1): 248–264. doi: 10.1111/imr.12635.Steinhoff M, Buddenkotte J, Lerner EA. Role of mast cells and basophils in pruritus. Immunol Rev. 2018; 282 (1): 248–264. doi: 10.1111/imr.12635.Liu F-T, Goodarzi H, Chen H-Y. IgE, mast cells, and eosinophils in atopic dermatitis. Clin Rev Allergy Immunol. 2011; 41 (3): 298–310. doi: 10.1007/s12016-011-8252-4.Liu F-T, Goodarzi H, Chen H-Y. IgE, mast cells, and eosinophils in atopic dermatitis. Clin Rev Allergy Immunol. 2011; 41 (3): 298–310. doi: 10.1007/s12016-011-8252-4.Sullivan M, Silverberg NB. Current and emerging concepts in atopic dermatitis pathogenesis. Clin Dermatol. 2017; 35 (4): 349–353. doi: 10.1016/j.clindermatol.2017.03.006.Sullivan M, Silverberg NB. Current and emerging concepts in atopic dermatitis pathogenesis. Clin Dermatol. 2017; 35 (4): 349–353. doi: 10.1016/j.clindermatol.2017.03.006.Hershey GK. IL-13 receptors and signaling pathways: an evolving web. J Allergy Clin Immunol. 2003; 111 (4): 677–691. doi: 10.1067/mai.2003.1333.Hershey GK. IL-13 receptors and signaling pathways: an evolving web. J Allergy Clin Immunol. 2003; 111 (4): 677–691. doi: 10.1067/mai.2003.1333.Fish SC, Donaldson DD, Goldman SJ, Williams CM, Kasaian MT. IgE generation and mast cell effector function in mice deficient in IL-4 and IL-13. J Immunol. 2005; 174 (12): 7716–7724. doi: 10.4049/jimmunol.174.12.7716.Fish SC, Donaldson DD, Goldman SJ, Williams CM, Kasaian MT. IgE generation and mast cell effector function in mice deficient in IL-4 and IL-13. J Immunol. 2005; 174 (12): 7716–7724. doi: 10.4049/jimmunol.174.12.7716.Mack MR, Kim BS. The Itch-Scratch Cycle: A Neuroimmune Perspective. Trends Immunol. 2018; 39 (12): 980–991. doi: 10.1016/j.it.2018.10.001.Mack MR, Kim BS. The Itch-Scratch Cycle: A Neuroimmune Perspective. Trends Immunol. 2018; 39 (12): 980–991. doi: 10.1016/j.it.2018.10.001.Schmelz M. Itch Processing in the Skin. Front Med (Lausanne). 2019; 6: 167. Published 2019 Jul 19. doi: 10.3389/fmed.2019.00167.Schmelz M. Itch Processing in the Skin. Front Med (Lausanne). 2019; 6: 167. Published 2019 Jul 19. doi: 10.3389/fmed.2019.00167.Nakashima C, Ishida Y, Kitoh A, Otsuka A, Kabashima K. Interaction of peripheral nerves and mast cells, eosinophils, and basophils in the development of pruritus. Exp Dermatol. 2019; 28 (12): 1405–1411. doi: 10.1111/exd.14014.Nakashima C, Ishida Y, Kitoh A, Otsuka A, Kabashima K. Interaction of peripheral nerves and mast cells, eosinophils, and basophils in the development of pruritus. Exp Dermatol. 2019; 28 (12): 1405–1411. doi: 10.1111/exd.14014.Bao L, Shi VY, Chan LS. IL-4 up-regulates epidermal chemotactic, angiogenic, and pro-inflammatory genes and down-regulates antimicrobial genes in vivo and in vitro: relevant in the pathogenesis of atopic dermatitis. Cytokine. 2013; 61 (2): 419–425. doi: 10.1016/j.cyto.2012.10.031.Bao L, Shi VY, Chan LS. IL-4 up-regulates epidermal chemotactic, angiogenic, and pro-inflammatory genes and down-regulates antimicrobial genes in vivo and in vitro: relevant in the pathogenesis of atopic dermatitis. Cytokine. 2013; 61 (2): 419–425. doi: 10.1016/j.cyto.2012.10.031.Bieber T. Interleukin-13: Targeting an underestimated cytokine in atopic dermatitis. Allergy. 2020; 75 (1): 54–62. doi: 10.1111/all.13954.Bieber T. Interleukin-13: Targeting an underestimated cytokine in atopic dermatitis. Allergy. 2020; 75 (1): 54–62. doi: 10.1111/all.13954.Moriya C, Jinnin M, Yamane K et al. Expression of matrix metalloproteinase-13 is controlled by IL-13 via PI3K/Akt3 and PKC-δ in normal human dermal fibroblasts. J Invest Dermatol. 2011; 131 (3): 655–661. doi: 10.1038/jid.2010.361.Moriya C, Jinnin M, Yamane K et al. Expression of matrix metalloproteinase-13 is controlled by IL-13 via PI3K/Akt3 and PKC-δ in normal human dermal fibroblasts. J Invest Dermatol. 2011; 131 (3): 655–661. doi: 10.1038/jid.2010.361.Guttman-Yassky E, Bissonnette R, Ungar B et al. Dupilumab progressively improves systemic and cutaneous abnormalities in patients with atopic dermatitis. J Allergy Clin Immunol. 2019; 143 (1): 155–172. doi: 10.1016/j.jaci.2018.08.022Guttman-Yassky E, Bissonnette R, Ungar B et al. Dupilumab progressively improves systemic and cutaneous abnormalities in patients with atopic dermatitis. J Allergy Clin Immunol. 2019; 143 (1): 155–172. doi: 10.1016/j.jaci.2018.08.022Wollenberg A, Beck LA, Blauvelt A et al. Laboratory safety of dupilumab in moderate-to-severe atopic dermatitis: results from three phase III trials (LIBERTY AD SOLO 1, LIBERTY AD SOLO 2, LIBERTY AD CHRONOS). Br J Dermatol. 2020; 182 (5): 1120–1135. doi: 10.1111/bjd.18434.Wollenberg A, Beck LA, Blauvelt A et al. Laboratory safety of dupilumab in moderate-to-severe atopic dermatitis: results from three phase III trials (LIBERTY AD SOLO 1, LIBERTY AD SOLO 2, LIBERTY AD CHRONOS). Br J Dermatol. 2020; 182 (5): 1120–1135. doi: 10.1111/bjd.18434.Simpson EL, Paller AS, Siegfried EC et al. Efficacy and Safety of Dupilumab in Adolescents With Uncontrolled Moderate to Severe Atopic Dermatitis: A Phase 3 Randomized Clinical Trial. JAMA Dermatol. 2020; 156 (1): 44–56. doi: 10.1001/jamadermatol.2019.3336.Simpson EL, Paller AS, Siegfried EC et al. Efficacy and Safety of Dupilumab in Adolescents With Uncontrolled Moderate to Severe Atopic Dermatitis: A Phase 3 Randomized Clinical Trial. JAMA Dermatol. 2020; 156 (1): 44–56. doi: 10.1001/jamadermatol.2019.3336.Paller AS, Siegfried EC, Thaçi D et al. Efficacy and safety of dupilumab with concomitant topical corticosteroids in children 6 to 11 years old with severe atopic dermatitis: A randomized, double-blinded, placebo-controlled phase 3 trial [published correction appears in J Am Acad Dermatol. 2021 Jan; 84 (1): 230]. J Am Acad Dermatol. 2020; 83 (5): 1282–1293. doi: 10.1016/j.jaad.2020.06.054.Paller AS, Siegfried EC, Thaçi D et al. Efficacy and safety of dupilumab with concomitant topical corticosteroids in children 6 to 11 years old with severe atopic dermatitis: A randomized, double-blinded, placebo-controlled phase 3 trial [published correction appears in J Am Acad Dermatol. 2021 Jan; 84 (1): 230]. J Am Acad Dermatol. 2020; 83 (5): 1282–1293. doi: 10.1016/j.jaad.2020.06.054.Thibodeaux Q, Smith MP, Ly K, Beck K, Liao W, Bhutani T. A review of dupilumab in the treatment of atopic diseases. Hum Vaccin Immunother. 2019; 15 (9): 2129–2139. doi: 10.1080/21645515.2019.1582403.Thibodeaux Q, Smith MP, Ly K, Beck K, Liao W, Bhutani T. A review of dupilumab in the treatment of atopic diseases. Hum Vaccin Immunother. 2019; 15 (9): 2129–2139. doi: 10.1080/21645515.2019.1582403.Paller AS, Siegfried EC, Thaçi D et al. Efficacy and safety of dupilumab with concomitant topical corticosteroids in children 6 to 11 years old with severe atopic dermatitis: A randomized, double-blinded, placebo-controlled phase 3 trial [published correction appears in J Am Acad Dermatol. 2021 Jan; 84 (1): 230]. J Am Acad Dermatol. 2020; 83 (5): 1282–1293. doi: 10.1016/j.jaad.2020.06.054.Paller AS, Siegfried EC, Thaçi D et al. Efficacy and safety of dupilumab with concomitant topical corticosteroids in children 6 to 11 years old with severe atopic dermatitis: A randomized, double-blinded, placebo-controlled phase 3 trial [published correction appears in J Am Acad Dermatol. 2021 Jan; 84 (1): 230]. J Am Acad Dermatol. 2020; 83 (5): 1282–1293. doi: 10.1016/j.jaad.2020.06.054.Инструкция по медицинскому применению лекарственного препарата Дупиксент® РУ № ЛП-005440 от 04. 04. 19 с изменениями от 16. 04. 21.Instructions for the medical use of the drug Dupixent® RU №. LP-005440 dated 04. 04. 19, as amended on 04. 16. 21. (in Russ.)https://clinicaltrials.gov/ct2/show/record/NCT03346434?term=dupilumab&cond=Atopic+Dermatitis&age=0&draw=2&rank=5https://clinicaltrials.gov/ct2/show/record/NCT03346434?term=dupilumab&cond=Atopic+Dermatitis&age=0&draw=2&rank=5https://clinicaltrials.gov/ct2/show/record/NCT02612454?term=dupilumab&cond=Atopic+Dermatitis&draw=2&rank=3https://clinicaltrials.gov/ct2/show/record/NCT02612454?term=dupilumab&cond=Atopic+Dermatitis&draw=2&rank=3Futamura M, Leshem YA, Thomas KS, Nankervis H, Williams HC, Simpson EL. A systematic review of Investigator Global Assessment (IGA) in atopic dermatitis (AD) trials: Many options, no standards. J Am Acad Dermatol. 2016; 74 (2): 288–294. doi: 10.1016/j.jaad.2015.09.062.Futamura M, Leshem YA, Thomas KS, Nankervis H, Williams HC, Simpson EL. A systematic review of Investigator Global Assessment (IGA) in atopic dermatitis (AD) trials: Many options, no standards. J Am Acad Dermatol. 2016; 74 (2): 288–294. doi: 10.1016/j.jaad.2015.09.062.Hanifin JM, Thurston M, Omoto M, Cherill R, Tofte SJ, Graeber M. The eczema area and severity index (EASI): assessment of reliability in atopic dermatitis. EASI Evaluator Group. Exp Dermatol. 2001; 10 (1): 11–18. doi: 10.1034/j.1600-0625.2001.100102.x.Hanifin JM, Thurston M, Omoto M, Cherill R, Tofte SJ, Graeber M. The eczema area and severity index (EASI): assessment of reliability in atopic dermatitis. EASI Evaluator Group. Exp Dermatol. 2001; 10 (1): 11–18. doi: 10.1034/j.1600-0625.2001.100102.x.Oranje AP, Glazenburg EJ, Wolkerstorfer A, de Waard-van der Spek FB. Practical issues on interpretation of scoring atopic dermatitis: the SCORAD index, objective SCORAD and the three-item severity score. Br J Dermatol. 2007; 157 (4): 645–648. doi: 10.1111/j.1365-2133.2007.08112.x.Oranje AP, Glazenburg EJ, Wolkerstorfer A, de Waard-van der Spek FB. Practical issues on interpretation of scoring atopic dermatitis: the SCORAD index, objective SCORAD and the three-item severity score. Br J Dermatol. 2007; 157 (4): 645–648. doi: 10.1111/j.1365-2133.2007.08112.x.Jang DH, Heo SJ, Kook HD et al. A 52 weeks dupilumab treatment for moderate to severe atopic dermatitis in Korea: long-term efficacy and safety in real world. Sci Rep. 2021; 11 (1): 235-239. Published 2021 Dec 7. doi: 10.1038/s41598-021-02950-4.Jang DH, Heo SJ, Kook HD et al. A 52 weeks dupilumab treatment for moderate to severe atopic dermatitis in Korea: long-term efficacy and safety in real world. Sci Rep. 2021; 11 (1): 235-239. Published 2021 Dec 7. doi: 10.1038/s41598-021-02950-4.Круглова ЛС, Шатохина ЕА, Руднева НC. Эффективность и безопасность дупилумаба в комплексном лечении пациентов с тяжелым атопическим дерматитом. Медицинский алфавит. 2021; 9: 39–43. doi: 10.33667/2078-5631-2021-9-39-43.Kruglova LS, Shatohina EA, Rudneva NC. Effektivnost’ i bezopasnost’ dupilumaba v kompleksnom lechenii pacientov s tyazhelym atopicheskim dermatitom. Medicinskij alfavit. 2021; 9: 39–43. (in Russ.)

The authors declare that there are no conflicts of interest present.