medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/2079-701X-2021-2-76-84medsovet-6015Research ArticleРЕВМАТОЛОГИЯRHEUMATOLOGYПрименение ингибиторов янус-киназ в терапии иммуновоспалительных ревматических заболеваний: вопросы безопасностиUse of Janus kinase inhibitors in the treatment of immunoinflammatory rheumatic diseases: safety issueshttps://orcid.org/0000-0001-7091-2054БеловБ. С.BelovB. S.

Белов Борис Сергеевич, д.м.н., заведующий лабораторией изучения коморбидных инфекций и мониторинга безопасности лекарственной терапии

115522, Москва, Каширское шоссе, д. 34а

Boris S. Belov, Dr. of Sci. (Med.), Head of the Laboratory for the Study of Comorbid Infections and Drug Therapy Safety Monitoring

34а, Kashirskoe Shosse, Moscow, 115522

belovbor@yandex.ruhttps://orcid.org/0000-0003-4327-6720МуравьеваН. В.MuravyevaN. V.

Муравьева Наталья Валерьевна, к.м.н., научный сотрудник лаборатории изучения коморбидных инфекций и мониторинга безопасности лекарственной терапии

115522, Москва, Каширское шоссе, д. 34а

Natalia V. Muravyeva, Cand. of Sci. (Med.), Researcher of the Laboratory for the Study of Comorbid Infections and Drug Therapy Safety Monitoring

34а, Kashirskoe Shosse, Moscow, 115522

n-muravjeva@mail.ruhttps://orcid.org/0000-0001-9933-5350ТарасоваГ. М.TarasovaG. M.

Тарасова Галина Михайловна, к.м.н., старший научный сотрудник лаборатории изучения коморбидных инфекций и мониторинга безопасности лекарственной терапии

115522, Москва, Каширское шоссе, д. 34а

Galina M. Tarasova, Cand. of Sci. (Med.), Senior Researcher of the Laboratory for the Study of Comorbid Infections and Drug Therapy Safety Monitoring

34а, Kashirskoe Shosse, Moscow, 115522

verizubgm@gmail.comhttps://orcid.org/0000-0002-5264-337XБарановаМ. М.BaranovaM. M.

Баранова Марина Михайловна, аспирант лаборатории изучения коморбидных инфекций и мониторинга безопасности лекарственной терапии

115522, Москва, Каширское шоссе, д. 34а

Marina M. Baranova, Postgraduate Student of the Laboratory for the Study of Comorbid Infections and Drug Therapy Safety Monitoring

34а, Kashirskoe Shosse, Moscow, 115522

efimova.marina.m@yandex.ruНаучно-исследовательский институт ревматологии им. В.А. НасоновойРоссияNasonova Research Institute of RheumatologyRussian Federation202111032021027684Copyright © Белов Б.С., Муравьева Н.В., Тарасова Г.М., Баранова М.М., 20212021Белов Б.С., Муравьева Н.В., Тарасова Г.М., Баранова М.М.Belov B.S., Muravyeva N.V., Tarasova G.M., Baranova M.M.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/6015

В последние десятилетия в ревматологии достигнут явный прогресс, связанный с внедрением в практику генно-инженерных биологических препаратов (ГИБП), а также таргетных базисных противовоспалительных препаратов, к которым относятся ингибиторы янус-киназ (и-JAK). На сегодняшний день и-JAK активно применяются и изучаются при различных иммуновоспалительных ревматических заболеваниях (ИВРЗ) – ревматоидном артрите, псориатическом артрите, анкилозирующем спондилите (АС), а также псориазе, атопическом дерматите и воспалительных заболеваниях кишечника. С целью обобщения накопленного опыта экспертами Европейской антиревматической лиги был разработан консенсус, в котором изложены основные принципы и положения, касающиеся рационального применения и-JAK у больных ИВРЗ. При этом большое внимание уделяется проблеме безопасности указанных лекарственных препаратов. В настоящей статье подробно рассмотрены вопросы, связанные с различными аспектами безопасности применения и-JAK у больных ИВРЗ, а именно: корректировка дозы в связи с лекарственными взаимодействиями, противопоказания, предварительный скрининг и оценка рисков. Проанализированы возможные нежелательные явления, касающиеся инфекционных осложнений, злокачественных новообразований, тромбоэмболических феноменов, перфорации желудочно-кишечного тракта. Подчеркнута значимость клинического и лабораторного мониторинга при катамнестическом наблюдении за больными, получающими и-JAK. Представлена программа дальнейших исследований по указанной проблеме. Она включает изучение эффективности и безопасности «переключения» между и-JAK у пациентов с плохой переносимостью конкретного препарата или не отвечающих на лечение, оценку влияния и-JAK на сопутствующие заболевания, включая сердечно-сосудистые болезни и остеопороз, исследование долгосрочной безопасности и-JAK, исходя из данных реальной практики, а также эффективности и безопасности комбинированной терапии и-JAK и ГИБП у пациентов с тяжелым РА или другими заболеваниями и т. д. Указанный консенсус разработан для информационной поддержки и адресован врачам, стремящимся достичь оптимального применения этих препаратов у больных ИВРЗ, а также самим пациентам и другим заинтересованным сторонам, включая администраторов лечебных учреждений. Несомненно, рекомендации будут расширены и дополнены по мере накопления новых данных.

There has been clear progress in rheumatology in recent decades with the introduction of genetically engineered biological drugs (GEBDs) as well as targeted baseline anti-inflammatory drugs, which include Janus kinase inhibitors (i-JAKs). To date, i-JAKs have been actively used and studied in various immunoinflammatory rheumatic diseases (IIRDs) – rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis (AS), as well as psoriasis, atopic dermatitis and inflammatory bowel disease. In order to summarize the accumulated experience, the experts of the European League Against Rheumatism developed a consensus, which outlined the main principles and provisions concerning the rational use of i-JAKS in patients with IIRDs. At the same time, much attention is paid to the problem of the safety of these drugs. In the present article, issues related to various aspects of the safety of the use of i-JAKs in patients with IIRDs are discussed in detail, namely: dose adjustments due to drug interactions, contraindications, pre-screening, and risk assessment. Possible adverse events related to infectious complications, malignancies, thromboembolic phenomena, and gastrointestinal perforation were analyzed. The significance of clinical and laboratory monitoring in catamnestic follow-up of patients receiving i-JAKs is emphasized. A program for further research on the mentioned problem is presented. It includes studies of the efficacy and safety of «switching» between i-JAKs in patients with poor tolerance of a particular drug or who do not respond to treatment, evaluation of the effect of i-JAKs on comorbidities including cardiovascular disease and osteoporosis, studies of the long-term safety of i-JAKs based on actual practice data, and of the effectiveness and safety of i-JAKs and GEBDs combination therapy in patients with severe RA or other conditions, etc. This consensus is designed to inform and target physicians seeking to achieve optimal use of these drugs in patients with IIRDs, as well as patients themselves and other interested parties, including facility administrators. The recommendations will undoubtedly be expanded and supplemented as new data accumulate.

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