antibioticsАнтибиотики и ХимиотерапияAntibiot Khimioter = Antibiotics and Chemotherapy0235-2990ООО «Издательство ОКИ»10.37489/0235-2990-2023-68-3-4-52-65antibiotics-1020Research ArticleКЛИНИЧЕСКИЕ ИССЛЕДОВАНИЯ И ПРАКТИКАGUIDELINES FOR PRACTITIONERSСистематический обзор с метаанализом и непрямым сравнением эффективности антиинтерлейкиновой терапии COVID-19A Systematic Review with Meta-Analysis and Indirect Comparison of the Effectiveness of COVID-19 Anti-Interleukin Therapyhttps://orcid.org/0000-0001-7704-9900ГомонЮ. М.GomonYu. M.

Гомон Юлия Михайловна — д. м. н., профессор кафедры клинической фармакологии и доказательной медицины; врач-клинический фармаколог

ул. Льва Толстого, д. 6–8, г. Санкт-Петербург, Россия, 197022

Yuliya M. Gomon — D. Sc. in Medicine, Professor of the Department of Clinical Pharmacology and Evidence-based Medicine; doctor-clinical pharmacologist

6–8 Lva Tolstogo str., St. Petersburg, 197022

gomonmd@yandex.ruhttps://orcid.org/0000-0002-1919-2909КолбинА. С.KolbinA. S.

Колбин Алексей Сергеевич — д. м. н., профессор, заведующий кафедрой клинической фармакологии и доказательной медицины; профессор кафедры фармакологии, медицинский факультет

Санкт-Петербург

Alexey A. Kolbin — D. Sc. in Medicine, Professor, Head of the Department of Clinical Pharmacology and Evidence-Based Medicine; Professor of the Department of Pharmacology, Faculty of Medicine

St. Petersburg

ФахрутдиноваА. М.FahrutdinovaA. M.

Фахрутдинова Айгуль Минсалиховна — врач-терапевт, пульмонолог, отделение терапии

Санкт-Петербург

Aigul M. Fahrutdinova — General practitioner, pulmonologist, Department of therapy, Department of Pharmacology

St. Petersburg

УсмановаТ. А.UsmanovaT. A.

Усманова Татьяна Андреевна — научный сотрудник, кафедра клинической фармакологии и доказательной медицины

Санкт-Петербург

Tatiana A. Usmanova — Researcher, Department of Clinical Pharmacology and Evidence-based Medicine

St. Petersburg

https://orcid.org/0000-0003-1626-6025СултановаФ. М.SultanovaF. M.

Султанова Флора Миргалимовна — координатор учебного центра РОЭХ

Санкт-Петербург

Flora M. Sultanova — Coordinator of the training center of the Russian Society of Endoscopic Surgeons

St. Petersburg

https://orcid.org/0000-0003-2143-0440БалыкинаЮ. Е.BalykinaYu. E.

Балыкина Юлия Ефимовна — к. ф-м. н., кафедра процессов управления, факультет прикладной математики

Санкт-Петербург

Yulia E. Balykina — PhD. Physical and mathematics sciences, Department of Management Processes, Faculty of Applied Mathematics

St. Petersburg

ФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет им. акад. И. П. Павлова» Минздрава России; СПб ГБУЗ «Больница Святого Великомученика Георгия»РоссияFirst St. Petersburg State Medical University named after Academician I. P. Pavlova Ministry of Health of Russia; Hospital of St. George the Great MartyrRussian FederationФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет им. акад. И. П. Павлова» Минздрава России; ФГБОУ ВО «Санкт-Петербургский государственный университет»РоссияFirst St. Petersburg State Medical University named after Academician I. P. Pavlova Ministry of Health of Russia; St. Petersburg State UniversityRussian FederationСПб ГБУЗ «Больница Святого Великомученика Георгия»РоссияHospital of St. George the Great MartyrRussian FederationФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет им. акад. И. П. Павлова» Минздрава РоссииРоссияFirst St. Petersburg State Medical University named after Academician I. P. Pavlova Ministry of Health of RussiaRussian FederationФГБОУ ВО «Санкт-Петербургский государственный университет»РоссияSt. Petersburg State UniversityRussian Federation202318072023683-45265Copyright © Гомон Ю.М., Колбин А.С., Фахрутдинова А.М., Усманова Т.А., Султанова Ф.М., Балыкина Ю.Е., 20232023Гомон Ю.М., Колбин А.С., Фахрутдинова А.М., Усманова Т.А., Султанова Ф.М., Балыкина Ю.Е.Gomon Y.M., Kolbin A.S., Fahrutdinova A.M., Usmanova T.A., Sultanova F.M., Balykina Y.E.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.antibiotics-chemotherapy.ru/jour/article/view/1020

Цель исследования. Оценка эффективности антиинтерлейкиновых лекарственных средств, используемых в рамках патогенетической терапии COVID-19 в отношении относительных рисков 28-дневной летальности и отношения шансов 14-дневного улучшения симптомов заболевания. Материал и методы. Проведён систематический обзор публикаций, касающихся оценки эффективности указанных лекарственных средств, рекомендованных к использованию в качестве патогенетической терапии COVID-19, с метаанализом и непрямым сравнением полученных данных. Результаты. В метаанализ было включено 15 рандомизированных и 8 нерандомизированных исследования. При прямом сравнении антиинтерлейкиновых ЛС с контролем было продемонстрировано, что только тоцилизумаб и анакинра превосходят стандартную терапию в отношении относительного риска 28-дневной летальности (ОР 0,85 [95% ДИ 0,74; 0,97] и 0,5 [95% ДИ 0,32; 0,80], соответственно). Также получены статистически достоверные данные в пользу эффективности левилимаба в сравнении со стандартной терапией по критерию «ОШ улучшения к 1-му дню заболевания», которое составило 2,29 [1,31; 4,01]. При непрямом сравнении тоцилизумаба и анакинры в отношении снижения ОР 28-дневной летальности последний показал большую эффективность: ОР составил 1,2 [95% ДИ 1,16; 1,25], р=0,0001. Выводы. Проведённый метаанализ результатов систематического обзора продемонстрировал эффективность тоцилизумаба и анакинры в отношении ОР 28-дневной летальности, а левилимаба в отношении показателя «ОШ Улучшение состояния к 14-му дню заболевания».

Aim. Evaluation of the effectiveness of anti-interleukin drugs used in the pathogenetic therapy of COVID-19 in relation to the relative risks of 28-day mortality and the odds ratio of 14-day improvement of symptoms of the disease. Materials and methods. A systematic review of publications concerning the evaluation of the effectiveness of these drugs recommended for use as COVID-19 pathogenetic therapy, with meta-analysis and indirect comparison of the data obtained, was carried out. Results. The meta-analysis included 15 randomized and 8 non-randomized studies. In direct comparison of anti-interleukin drugs with controls, it was demonstrated that only tocilizumab and anakinra surpass standard therapy in terms of the relative risk of 28-day mortality (RR 0.85 [95% CI 0.74; 0.97] and 0.5 [95% CI 0.32; 0.80], respectively). Statistically reliable data were also obtained in favor of the effectiveness of levilimab in comparison with standard therapy according to the criterion of «improvement by the 14th day of the disease», which was 2.29 [1.31; 4.01]. With an indirect comparison of tocilizumab and anakinra, the latter showed greater effectiveness in reducing the 28-day mortality rate: the RR was 1.2 [95% CI 1.16; 1.25], P=0.0001. Conclusion. The meta-analysis of the results of the systematic review demonstrated the effectiveness of tocilizumab and anakinra in relation to the 28-day mortality rate, and levilimab in relation to the indicator «Improvement by the 14th day of the disease».

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