medalphabetМедицинский алфавитMedical alphabet2078-56312949-2807ООО «Альфмед»10.33667/2078-5631-2020-31-21-26medalphabet-1812Research ArticleСтатьиИнгибиторы янус-киназ и инфекции у больных ревматологического профиляInhibitors of janus kinases and infection in patients of rheumatologic profileБеловБ. С.BelovB. S.

Доктор медицинских наук, заведующий лабораторией изучения коморбидных инфекций и мониторинга безопасности лекарственной терапии.

Москва

Moscow

МуравьеваН. В.MuravyovaN. V.

Кандидат медицинских наук, научный сотрудник лаборатории изучения коморбидных инфекций и мониторинга безопасности лекарственной терапии.

Москва

Moscow

ТарасоваГ. М.TarasovaG. M.

Кандидат медицинских наук старший научный сотрудник лаборатории изучения коморбидных инфекций и мониторинга безопасности лекарственной терапии.

Москва

Moscow

БарановаМ. М.BaranovaM. M.

Аспирант

Москва

Moscow

ФГБНУ Научно-исследовательский институт ревматологии имени В.А. НасоновойРоссияV.A. Nasonova Research Institute of RheumatologyRussian Federation202011012021031Ревматология в общей практике (2)2126Copyright © 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., Muravyova 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-alphabet.com/jour/article/view/1812

В последние десятилетия в ревматологии отмечается явный прогресс, связанный с внедрением в практику генно-инженерных биологических препаратов, а также таргетных базисных противовоспалительных препаратов (тБПВП), к которым относятся ингибиторы янус-киназ. В то же время применение этих препаратов ассоциируется с нарастающим риском развития инфекций разнообразной природы и локализации, а также реактивации латентной инфекции. Помимо этого, регистрируются случаи тяжелых инфекций, в том числе с летальным исходом. В настоящем обзоре проанализированы данные литературы преимущественно последних 5 лет, касающиеся частоты и локализации основных коморбидных инфекций у больных ревматоидным артритом и псориатическим артритом при лечении различными тБПВП (тофацитиниб, барицитиниб, упадацитиниб). Охарактеризована значимость инфекций (туберкулез, герпес-вирусные инфекции, хронический вирусный гепатит В) в тактике курации указанных больных. Подчеркнута необходимость более широкого применения иммунизации различными вакцинами (в первую очередь пневмококковой и гриппозной) пациентов с иммуно-воспалительными ревматическими заболеваниями.

In recent decades, there has been clear progress in rheumatology associated with the introduction of genetically engineered biological drugs, as well as targeted basic anti-inflammatory drugs (tBPVP), which include Janus kinase inhibitors. At the same time, the use of these drugs is associated with an increasing risk of developing infections of various nature and localization, as well as reactivation of latent infection. In addition, cases of severe infections, including fatal ones, are registered. This review analyzes the literature data, mainly from the last 5 years, concerning the frequency and localization of major comorbid infections in patients with rheumatoid arthritis and psoriatic arthritis in the treatment of various tBPVS (tofacitinib, baricitinib, upadacitinib). The significance of infections (tuberculosis, herpes-viral infections, chronic viral hepatitis B) in the management of these patients is characterized. The need for a wider use of various vaccines (primarily anti-pneumococcal and anti-influenza) in patients with immuno-inflammatory rheumatic diseases is emphasized.

таргетные базисные противовоспалительные препаратыингибиторы янус-киназтофацитиниббарицитинибупадацитинибинфекциивакцинацияtargeted basic anti-inflammatory drugsJanus kinase inhibitorstofacitinibbaricitinibupadacitinibinfectionsvaccinationReferencesSokka T, Abelson B, Pincus T. Mortality in rheumatoid arthritis: 2008 update. Clin Exp Rheumatol. 2008; 26 (5 Suppl 51): 35-61.Sokka T, Abelson B, Pincus T. Mortality in rheumatoid arthritis: 2008 update. Clin Exp Rheumatol. 2008; 26 (5 Suppl 51): 35-61.Белов Б. С., Балабанова Р. М., Манукян С. Г. и др. Коморбидные инфекции при ревматических заболеваниях. XVI Росс. нац. конгр. Человек и лекарство: Тез. докл. М., 2007. С. 527Belov B. S., Balabanova R. M., Manukyan S. G., i dr. Komorbidnye infekcii pri revmaticheskih zabolevaniyah. XVI Ross. nac. kongr. «Chelovek i lekarstvo»: Tez. dokl. M., 2007. S. 527. (In Russ.).Doran MF, Crowson CS, Pond GR, et al. Frequency of infection in patients with rheumatoid arthritis compared with controls: a population-based study. Arthritis Rheum. 2002; 46 (9): 22872293.Doran MF, Crowson CS, Pond GR, et al. Frequency of infection in patients with rheumatoid arthritis compared with controls: a population-based study. Arthritis Rheum. 2002; 46 (9): 22872293.Doran MF, Crowson CS, Pond GR, et al. Predictors of infection in rheumatoid arthritis. Arthritis Rheum. 2002; 46 (9): 2294-2300.Doran MF, Crowson CS, Pond GR, et al. Predictors of infection in rheumatoid arthritis. Arthritis Rheum. 2002; 46 (9): 2294-2300.van der Veen MJ., van der Heide A., Kruize AA., Bijlsma JWJ. Infection rate and use antibiotics in patients with rheumatoid arthritis treated with methotrexate. Ann. Rheum. Dis., 1994; 53: 224-228.van der Veen MJ., van der Heide A., Kruize AA., Bijlsma JWJ. Infection rate and use antibiotics in patients with rheumatoid arthritis treated with methotrexate. Ann. Rheum. Dis., 1994; 53: 224-228.Kao LT, Lee CZ, Liu SP, et al. Psoriasis and the risk of pneumonia: a population-based study. PLoS One. 2014; 9 (12): e116077. DOI: 10.1371/journal.pone.0116077Kao LT, Lee CZ, Liu SP, et al. Psoriasis and the risk of pneumonia: a population-based study. PLoS One. 2014; 9 (12): e116077. DOI: 10.1371/journal.pone.0116077Haddad A, Li S, Thavaneswaran A, et al. The Incidence and Predictors of Infection in Psoriasis and Psoriatic Arthritis: Results from Longitudinal Observational Cohorts. J Rheumatol. 2016; 43 (2): 362-6. DOI: 10.3899/jrheum.140067.Haddad A, Li S, Thavaneswaran A, et al. The Incidence and Predictors of Infection in Psoriasis and Psoriatic Arthritis: Results from Longitudinal Observational Cohorts. J Rheumatol. 2016; 43 (2): 362-6. DOI: 10.3899/jrheum.140067.Cohen SB, Tanaka Y, Mariette X, et al. Long-term safety of tofacitinib up to 9.5 years: a comprehensive integrated analysis of the rheumatoid arthritis clinical development programme. RMD Open. 2020 Oct; 6 (3): e001395. DOI: 10.1136/rmdopen-2020-001395.Cohen SB, Tanaka Y, Mariette X, et al. Long-term safety of tofacitinib up to 9.5 years: a comprehensive integrated analysis of the rheumatoid arthritis clinical development programme. RMD Open. 2020 Oct; 6 (3): e001395. DOI: 10.1136/rmdopen-2020-001395.Winthrop KL, Harigai M, Genovese MC, et al. Infections in baricitinib clinical trials for patients with active rheumatoid arthritis. Ann Rheum Dis. 2020 Oct; 79 (10): 1290-1297. DOI: 10.1136/annrheumdis-2019-216852.Winthrop KL, Harigai M, Genovese MC, et al. Infections in baricitinib clinical trials for patients with active rheumatoid arthritis. Ann Rheum Dis. 2020 Oct; 79 (10): 1290-1297. DOI: 10.1136/annrheumdis-2019-216852.Cohen SB, van Vollenhoven RF, Winthrop KL, et al. Safety profile of upadacitinib in rheumatoid arthritis: integrated analysis from the SELECT phase III clinical programme. Ann Rheum Dis. 2020 Oct 28: annrheumdis-2020-218510. DOI: 10.1136/annrheumdis-2020-218510.Cohen SB, van Vollenhoven RF, Winthrop KL, et al. Safety profile of upadacitinib in rheumatoid arthritis: integrated analysis from the SELECT phase III clinical programme. Ann Rheum Dis. 2020 Oct 28: annrheumdis-2020-218510. DOI: 10.1136/annrheumdis-2020-218510.Новые рекомендации ВОЗ по профилактике туберкулеза призваны спасти миллионы жизней. 24 марта 2020 г. Пресс-релиз. Женева. Режим доступа: https://www.who.int/ru/news/item/24-03-2020-new-who-recommendations-to-prevent-tuberculosis-aim-to-save-millions-of-livesNovye rekomen-dacii VOZ po profilaktike tuberkuleza priz-vany spasti milliony zhiznej. 24 marta 2020 g. Press-reliz. Geneva. (In Russ.). Available at: https://www.who.int/ru/news/item/24-03-2020-new-who-recommendations-to-prevent-tuberculosis-aim-to-save-millions-of-lives.Лукина Г. В., Борисов С. Е. Скрининг и мониторинг туберкулезной инфекции у больных ревматическими заболеваниями, получающими генно-инженерные биологические препараты. В кн. Российские рекомендации. Ревматология. Под ред. Е. Л. Насонова.М., ГЭОТАР-Медиа, 2017. С. 394-410Lukina G. V., Borisov S. E. Skrining i monitoring tuberkuleznoj infekcii u bol’nyh revmaticheskimi zabolevani-yami, poluchayushchimi genno-inzhenernye biologicheskie preparaty. V kn. Rossijskie re-komendacii. Revmatologiya. Pod red. E. L. Nasonova.M., GEOTAR-Media, 2017. S. 394-410. (In Russ.).Winthrop KL, Yamanaka H, Valdez H, et al. Herpes zoster and tofacitinib therapy in patients with rheumatoid arthritis. Arthritis Rheumatol. 2014 Oct; 66 (10): 2675-84. DOI: 10.1002/art.38745.Winthrop KL, Yamanaka H, Valdez H, et al. Herpes zoster and tofacitinib therapy in patients with rheumatoid arthritis. Arthritis Rheumatol. 2014 Oct; 66 (10): 2675-84. DOI: 10.1002/art.38745.Burmester GR, Curtis JR, Yun H, et al. An Integrated Analysis of the Safety of Tofacitinib in Psoriatic Arthritis across Phase III and Long-Term Extension Studies with Comparison to Real-World Observational Data. Drug Saf. 2020 Apr; 43 (4): 379-392. DOI: 10.1007/s40264-020-00904-9.Burmester GR, Curtis JR, Yun H, et al. An Integrated Analysis of the Safety of Tofacitinib in Psoriatic Arthritis across Phase III and Long-Term Extension Studies with Comparison to Real-World Observational Data. Drug Saf. 2020 Apr; 43 (4): 379-392. DOI: 10.1007/s40264-020-00904-9.Atzeni F, Talotta R, Nucera V, et al. Adverse events, clinical considerations and management recommendations in rheumatoid arthritis patients treated with JAK inhibitors. Expert Rev Clin Immunol. 2018; 14 (11): 945-956. DOI: 10.1080/1744666X.2018.1504678.Atzeni F, Talotta R, Nucera V, et al. Adverse events, clinical considerations and management recommendations in rheumatoid arthritis patients treated with JAK inhibitors. Expert Rev Clin Immunol. 2018; 14 (11): 945-956. DOI: 10.1080/1744666X.2018.1504678.Almanzar G, Kienle F, Schmalzing M et al. To-facitinib modulates the VZV-specific CD 4+ T cell immune response in vitro in lymphocytes of patients with rheumatoid arthritis. Rheumatology. 2019; 58 (11): 2051-2060. DOI: 10.1093/rheumatology/kez175.Almanzar G, Kienle F, Schmalzing M et al. To-facitinib modulates the VZV-specific CD 4+ T cell immune response in vitro in lymphocytes of patients with rheumatoid arthritis. Rheumatology. 2019; 58 (11): 2051-2060. DOI: 10.1093/rheumatology/kez175.Chen YM, Huang WN, Wu YD, et al. Reactivation of hepatitis B virus infection in patients with rheumatoid arthritis receiving tofaci-tinib: a real-world study. Ann Rheum Dis. 2018; 77 (5): 780-782. DOI: 10.1136/annrheum-dis-2017-211322.Chen YM, Huang WN, Wu YD, et al. Reactivation of hepatitis B virus infection in patients with rheumatoid arthritis receiving tofaci-tinib: a real-world study. Ann Rheum Dis. 2018; 77 (5): 780-782. DOI: 10.1136/annrheum-dis-2017-211322.Harigai M, Winthrop K, Takeuchi T, et al. Evaluation of hepatitis B virus in clinical trials of baricitinib in rheumatoid arthritis. RMD Open. 2020 Feb; 6 (1): e001095. DOI: 10.1136/rm-dopen-2019-001095.Harigai M, Winthrop K, Takeuchi T, et al. Evaluation of hepatitis B virus in clinical trials of baricitinib in rheumatoid arthritis. RMD Open. 2020 Feb; 6 (1): e001095. DOI: 10.1136/rm-dopen-2019-001095.Koutsianas C, Thomas K, Vassilopoulos D. Reactivation of hepatitis B virus infection in rheumatic diseases: risk and management considerations. Ther Adv Musculoskelet Dis. 2020 Mar 16; 12:1759720X20912646. DOI: 10.1177/1759720X20912646.Koutsianas C, Thomas K, Vassilopoulos D. Reactivation of hepatitis B virus infection in rheumatic diseases: risk and management considerations. Ther Adv Musculoskelet Dis. 2020 Mar 16; 12:1759720X20912646. DOI: 10.1177/1759720X20912646.Furer V, Rondaan C, Heijstek MW et al. 2019 update of EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases.Ann Rheum Dis. 2020 Jan; 79 (1): 39-52. DOI: 10.1136/ann-rheumdis-2019-215882.Furer V, Rondaan C, Heijstek MW et al. 2019 update of EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases.Ann Rheum Dis. 2020 Jan; 79 (1): 39-52. DOI: 10.1136/ann-rheumdis-2019-215882.Baumrin E, van Voorhees A, Garg A, et al. A systematic review of herpes zoster incidence and consensus recommendations on vaccination in adult patients on systemic therapy for psoriasis or psoriatic arthritis: From the Medical Board of the National Psoriasis Foundation. J Am Acad Dermatol. 2019 Jul; 81 (1): 102-110. DOI: 10.1016/j.jaad.2019.03.017.Baumrin E, van Voorhees A, Garg A, et al. A systematic review of herpes zoster incidence and consensus recommendations on vaccination in adult patients on systemic therapy for psoriasis or psoriatic arthritis: From the Medical Board of the National Psoriasis Foundation. J Am Acad Dermatol. 2019 Jul; 81 (1): 102-110. DOI: 10.1016/j.jaad.2019.03.017.

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