References

medsovet

Медицинский Совет

Meditsinskiy sovet = Medical Council

2079-701X2658-5790

REMEDIUM GROUP Ltd.

10.21518/2079-701X-2019-18-85-91

medsovet-4970

Research Article

РЕВМАТОЛОГИЯ

RHEUMATOLOGY

Ингибитор биологических эффектов интерлейкина-6 сарилумаб в терапии ревматоидного артрита

Inhibitor of biological effects of interleukin-6 sarilumab in treatment of rheumatoid arthritis

https://orcid.org/0000-0002-2352-4080

Каратеев

Д. Е.

Karateev

D. E.

Каратеев Дмитрий Евгеньевич, д.м.н., заведующий отделением ревматологии, профессор кафедры терапии

Dmitry E. Karateev, Dr. of Sci. (Med), Head of the Rheumatology Department, Professor of the Department of Therapy

61/2, Schepkina str., Moscow, 129110

dekar@inbox.ru

https://orcid.org/0000-0002-6519-1106

Лучихина

Е. Л.

Luchikhina

E. L.

Лучихина Елена Львовна, к.м.н., ведущий научный сотрудник отделения ревматологии, доцент кафедры терапии

129110, Москва, ул. Щепкина, д. 61/2

Elena L. Luchikhina, Cand. of Sci. (Med), Leading Researcher at the Rheumatology Department, Associate Professor at the Department of Therapy

61/2, Schepkina str., Moscow, 129110

Московский областной научно-исследовательский клинический институт им. М.Ф. ВладимирскогоРоссияState Budgetary Healthcare Institution of the Moscow Region «Moscow Regional Research and Clinical Institute named after M.F. Vladimirsky»Russian Federation

2019

01122019

0188591

2019

Каратеев Д.Е., Лучихина Е.Л.

Karateev D.E., Luchikhina E.L.

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/4970

Несмотря на прогресс фармакотерапии, сохраняется насущная потребность в разработке новых методов медикаментозного лечения ревматоидного артрита (РА). Перспективы лекарственной терапии в настоящее время связывают с препаратом сарилумаб (САР), недавно зарегистрированным в Российской Федерации для лечения РА с умеренной и высокой активностью у взрослых пациентов. САР связывается как с мембранными, так и с растворимыми рецепторами интерлейкина-6 (ИЛ-6р), блокируя его провоспалительные эффекты. САР имеет определенные отличия от своего предшественника тоцилизумаба: представляет собой полностью человеческое, а не гуманизированное антитело, вводится 1 раз в 2 недели подкожно, обладает более выраженной аффинностью в отношении ИЛ-6р. САР является высокоэффективным средством лечения больных РА, он продемонстрировал более высокую эффективность в монотерапии по сравнению с представителем класса ингибиторов ФНО (и-ФНО) адалимумабом. Клинические исследования показали приблизительно равные параметры клинической эффективности и безопасности САР и тоцилизумаба. Сарилумаб следует рассматривать как препарат первого ряда в биологической терапии РА с высокой воспалительной активностью, а также при резистентности к и-ФНО.

Despite progress in pharmacotherapy, there still are urgent needs in the development of new methods of drug therapy of rheumatoid arthritis (RA). New prospects for drug therapy are currently associated with sarilumab (SAR), recently registered in the Russian Federation for the treatment of moderate to highly active RA in adult patients. SAR binds to both membrane and soluble interleukin-6 receptors (IL-6r), blocking its pro-inflammatory effect. SAR has certain differences from its predecessor, tocilizumab: it is a fully human, not humanized, antibody, it is injected subcutaneously once every 2 weeks, it has a more pronounced affinity for IL-6r. SAR is a highly effective treatment for patients with RA, it has shown higher efficacy in monotherapy compared to the representative of the class of TNF inhibitors adalimumab. Clinical studies have shown approximately equal clinical efficacy parameters and a safety profile for SAR and tocilizumab. Sarilumab should be considered as a first-line biologic drug in patients with high inflammatory activity, as well as in patients resistant to anti-TNF.

ревматоидный артритсарилумабинтерлейкин-6

rheumatoid arthritissarilumabinterleukin-6

References1

Ferro F., Elefante E., Luciano N., Talarico R., Todoerti M. One year in review 2017: novelties in the treatment of rheumatoid arthritis. Clin Exp Rheumatol. 2017;35(5):721-734. Available at: https://www.ncbi.nlm.nih.gov/ pubmed/28956527.

Pedersini R., Karateev D.E., Vasilescu R.S., Alvir J.M., Spurden D., Smolen J.S. The Burden of Rheumatoid Arthritis in Russia. Value Health. 2015;18(7):A651. doi: 10.1016/j.jval.2015.09.2344.

Smolen J.S., Aletaha D., McInnes I.B. Rheumatoid arthritis. Lancet. 2016;388(10055):2023-2038. doi: 10.1016/S0140-6736(16)30173-8.

Smolen J.S., Aletaha D., McInnes I.B. Rheumatoid arthritis. Lancet. 2016;388(10055):2023-2038. doi: 10.1016/ S0140-6736(16)30173-8.

Насонов Е.Л., Каратеев Д.Е. Ревматоидный артрит. В кн.: Насонов Е.Л. (ред.). Российские клинические рекомендации. Ревматология. М.: ГЭОТАР-Медиа; 2017. 464 с.

Nasonov E.L., Karateev D.E. Rheumatoid arthritis. In: Nasonov E.L. (red.). Russian clinical recommendations. Rheumatology.: Moscow: GEOTAR-Media; 2017. 464 p. (In Russ.)

Smolen J.S., Landewé R., Bijlsma J., Burmester G., Chatzidionysiou K., Dougados M., et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis. 2017;76(6):960977. doi: 10.1136/annrheumdis-2016-210715.

Kaltsonoudis E., Pelechas E., Voulgari P.V., Drosos A.A. Unmet needs in the treatment of rheumatoid arthritis. An observational study and a reallife experience from a single university center. Semin Arthritis Rheum. 2019;48(4):597–602. doi:10.1016/j.semarthrit.2018.06.003.

Kaltsonoudis E., Pelechas E., Voulgari P.V., Drosos A.A. Unmet needs in the treatment of rheumatoid arthritis. An observational study and a real-life experience from a single university center. Semin Arthritis Rheum. 2019;48(4):597–602. doi:10.1016/j.semarthrit.2018.06.003.

Drosos A.A., Pelechas E., Voulgari P.V. Rheumatoid arthritis treatment. A back to the drawing board project or high expectations for low unmet needs? J Clin Med. 2019;8(8):pii. E1237. doi:10.3390/jcm8081237.

Narazaki M., Tanaka T., Kishimoto T. The role and therapeutic targeting of IL-6 in rheumatoid arthritis. Expert Rev Clin Immunol. 2017;13(6):535551. doi: 10.1080/1744666X.2017.1295850.

Narazaki M., Tanaka T., Kishimoto T. The role and therapeutic targeting of IL-6 in rheumatoid arthritis. Expert Rev Clin Immunol. 2017;13(6):535-551. doi: 10.1080/1744666X.2017.1295850.

Насонов Е.Л., Каратеев Д.Е. Применение генно-инженерных биологических препаратов для лечения ревматоидного артрита: общая характеристика (лекция). Научнопрактическая ревматология. 2013;51(2):163-169. doi: 10.14412/19954484-2013-645.

Nasonov E.L., Karateev D.E. Use of genetically engineered biological agents for the treatment of rheumatoid arthritis: general characteristics (a lecture). Rheumatology Science and Practice. 2013;51(2):163-169. (In Russ.) doi: 10.14412/1995-4484-2013-645.

Kang S., Tanaka T., Kishimoto T. Therapeutic uses of anti-interleukin-6 receptor antibody. Int Immunol. 2015;27(1):21-29. doi: 10.1093/ intimm/dxu081.

Wong P.K., Campbell I.K., Egan P.J., Ernst M., Wicks I.P. The role of the interleukin-6 family of cytokines in inflammatory arthritis and bone turnover. Arthritis Rheum. 2003;48(5):1177-1189. doi: 10.1002/art.10943.

Chung S.J., Kwon Y.J., Park M.C., Park Y.B., Lee S.K. The correlation between increased serum concentrations of interleukin-6 family cytokines and disease activity in rheumatoid arthritis patients. Yonsei Med J. 2011;52(1):113120. doi: 10.3349/ymj.2011.52.1.113.

Kotake S., Sato K., Kim K.J., Takahashi N., Udagawa N., Nakamura I., Yamaguchi A., Kishimoto T., Suda T., Kashiwazaki S. Interleukin-6 and soluble interleukin-6 receptors in the synovial fluids from rheumatoid arthritis patients are responsible for osteoclast-like cell formation. J Bone Miner Res. 1996;11(1):88-95 doi: 10.1002/jbmr.5650110113.

Avci A.B., Feist E., Burmester G.R. Targeting IL-6 or IL-6 Receptor in Rheumatoid Arthritis: What’s the Difference? BioDrugs. 2018;32(6):531-546. doi: 10.1007/s40259-018-0320-3.

Emery P., Keystone E., Tony H.P., Cantagrel A., van Vollenhoven R., Sanchez A., Alecock E., Lee J., Kremer J. IL-6 receptor inhibition with tocilizumab improves treatment outcomes in patients with rheumatoid arthritis refractory to antitumour necrosis factor biologicals: results from a 24-week multicentre randomised placebo-controlled trial. Ann Rheum Dis. 2008;67(11):15161523. doi: 10.1136/ard.2008.092932.

Lauper K., Nordström D.C., Pavelka K., Hernández M.V., Kvien T.K., Kristianslund E.K., et al. Comparative effectiveness of tocilizumab versus TNF inhibitors as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis after the use of at least one biologic disease-modifying antirheumatic drug: analyses from the panEuropean TOCERRA register collaboration. Ann Rheum Dis. 2018;77(9):1276-1282. doi: 10.1136/annrheumdis-2017-212845.

Панасюк Е.Ю., Амирджанова В.Н., Авдеева А.С., Лучихина Е.Л., Александрова Е.Н., Новиков А.А., Насонов Е.Л. Опыт применения тоцилизумаба у больных ревматоидным артритом (по данным многоцентрового исследования ЛОРНЕТ). Научнопрактическая ревматология. 2013;51(2):104-110. doi: doi: 10.14412/1995-4484-2013-635.

Panasyuk E.Y., Amirdzhanova V.N., Avdeyeva A.S., Luchikhina E.L., Aleksandrova E.N., Novikov A.A., Nasonov E.L. Experience with tocilizumab in patients with rheumatoid arthritis (according to the data of the LORNET multicenter trial). Rheumatology Science and Practice. 2013;51(2):104-110. (In Russ.) doi: 10.14412/1995-4484-2013-635.

Scott L.J. Tocilizumab: A Review in Rheumatoid Arthritis. Drugs. 2017;77(17):1865-1879. doi: 10.1007/s40265-017-0829-7.

McCarty D., Robinson A. Efficacy and safety of sarilumab in patients with active rheumatoid arthritis. Ther Adv Musculoskelet Dis. 2018;10(3):6167. doi: 10.1177/1759720X17752037.

Rafique A., Martin J., Blome M., Huang T., Ouyang A., Papadopoulos N. AB0037 Evaluation of the binding kinetics and functional bioassay activity of sarilumab and tocilizumab to the human il-6 receptor (il-6r) alpha. Annals of the Rheumatic Diseases. 2014;72(Suppl 3):A797-A797 doi: 10.1136/ annrheumdis-2013-eular.2360.

Xu C., Nolain P., Lu Q., Paccaly A., IglesiasRodriguez M., St John G., Nivens C., Maldonado R., Ishii T., Choy E., Kanamaluru V. FRI0106 Sarilumab and tocilizumab receptor occupancy (RO), and effects on C-reactive protein (CRP) levels, in patients with rheumatoid arthritis (RA). Annals of the Rheumatic Diseases. 2019;(78):719720. doi: 10.1136/annrheumdis-2019-eular.3324.

Huizinga T.W., Fleischmann R.M., Jasson M., Radin A.R., van Adelsberg J., Fiore S., Huang X., Yancopoulos G.D., Stahl N., Genovese M.C. Sarilumab, a fully human monoclonal antibody against IL-6Rα in patients with rheumatoid arthritis and an inadequate response to methotrexate: efficacy and safety results from the randomised SARIL-RA-MOBILITY Part A trial. Ann Rheum Dis. 2014;73(9):1626-1634. doi: 10.1136/annrheumdis-2013-204405.

Genovese M.C., Fleischmann R., Kivitz A.J., RellBakalarska M., Martincova R., Fiore S., et al. Sarilumab Plus Methotrexate in Patients With Active Rheumatoid Arthritis and Inadequate Response to Methotrexate: Results of a Phase III Study. Arthritis Rheumatol. 2015;67(6):14241437. doi: 10.1002/art.39093.

Strand V., Kosinski M., Chen C.I., Joseph G., Rendas-Baum R., Graham N.M., et al. Sarilumab plus methotrexate improves patient-reported outcomes in patients with active rheumatoid arthritis and inadequate responses to methotrexate: results of a phase III trial. Arthritis Res Ther. 2016;(18):198. doi: 10.1186/s13075-016-1096-9.

Насонов Е.Л., Станислав М.Л., Раскина Т.А., Куропаткин Г.В., Ширинский И.В., Ребров А.П., Шостак Н.А., Алиханов Б.А., Ушакова Е.Н., Камалова Р.Г., Смакотина С.А., Симаненков В.И., Повзун А.С., Захарьян И.И., Якушин С.С., Сандин М.Ю. Эффективность и безопасность сарилумаба в комбинации с метотрексатом у пациентов с активным ревматоидным артритом и неадекватным эффектом монотерапии метотрексатом (результаты исследования III фазы по протоколу MOBILITY). Научнопрактическая ревматология. 2019;57(2):142148. doi: 10.14412/1995-4484-2019-142-148.

Nasonov E.L., Stanislav M.L., Raskina T.A., Kuropatkin G.V., Shirinsky I.V., Rebrov A.P., Shostak N.A., Alikhanov B.A., Ushakov E.N., Kamalova R.G., Smakotina S.A., Simanenkov V.I., Pavsun A.S., Zaharjan I.I., Yakushin S.S., Sandin M.Y. Efficacy and safety of sarilumab in combination with methotrexate in patients with active rheumatoid arthritis and inadequate effect of methotrexate monotherapy (results of phase III MOBILITY study). Rheumatology Science and Practice. 2019;57(2):142-148. (In Russ.) doi: 10.14412/1995-4484-2019-142-148.

Boyapati A., Msihid J., Fiore S., van Adelsberg J., Graham N.M., Hamilton J.D. Sarilumab plus methotrexate suppresses circulating biomarkers of bone resorption and synovial damage in patients with rheumatoid arthritis and inadequate response to methotrexate: a biomarker study of MOBILITY. Arthritis Res Ther. 2016;18(1):225. doi: 10.1186/s13075-016-1132-9.

Emery P., Rondon J., Parrino J., Lin Y., Pena-Rossi C., van Hoogstraten H., Graham N.M.H., Liu N., Paccaly A., Wu R., Spindler A. Safety and tolerability of subcutaneous sarilumab and intravenous tocilizumab in patients with rheumatoid arthritis. Rheumatology (Oxford). 2018;(58):849858. doi: 10.1093/rheumatology/key361.

Fleischmann R., van Adelsberg J., Lin Y., Castelar-Pinheiro G.D., Brzezicki J., Hrycaj P., Graham N.M., van Hoogstraten H., Bauer D., Burmester G.R. Sarilumab and Nonbiologic Disease-Modifying Antirheumatic Drugs in Patients With Active Rheumatoid Arthritis and Inadequate Response or Intolerance to Tumor Necrosis Factor Inhibitors. Arthritis Rheumatol. 2017;69(2):277-290. doi: 10.1002/art.39944.

Gabay C., Msihid J., Zilberstein M., Paccard C., Lin Y., Graham N.M.H., Boyapati A. Identification of sarilumab pharmacodynamic and predictive markers in patients with inadequate response to TNF inhibition: a biomarker substudy of the phase 3 TARGET study. RMD Open. 2018;4(1):e000607. doi: 10.1136/rmdopen-2017-000607.

Burmester G.R., Lin Y., Patel R., van Adelsberg J., Mangan E.K., Graham N.M., et al. Efficacy and safety of sarilumab monotherapy versus adalimumab monotherapy for the treatment of patients with active rheumatoid arthritis (MONARCH): a randomised, double-blind, parallel-group phase III trial. Ann Rheum Dis. 2017;76(5):840-847. doi: 10.1136/annrheumdis-2016-210310.

Strand V., Gossec L., Proudfoot C.W.J., Chen C.I., Reaney M., Guillonneau S., et al. Patientreported outcomes from a randomized phase III trial of sarilumab monotherapy versus adalimumab monotherapy in patients with rheumatoid arthritis. Arthritis Res Ther. 2018;20(1):129. doi: 10.1186/s13075-0181614-z.

Wells A.F., Parrino J., Mangan E.K., Paccaly A., Lin Y., Xu C., et al. Immunogenicity of Sarilumab Monotherapy in Patients with Rheumatoid Arthritis Who Were Inadequate Responders or Intolerant to Disease-Modifying Antirheumatic Drugs. Rheumatol Ther. 2019;6(3):339-352. doi: 10.1007/s40744-019-0157-3.

Wells A.F., Parrino J., Mangan E.K., Paccaly A., Lin Y., Xu C., et al. Immunogenicity of Sarilumab Monotherapy in Patients with Rheumatoid Arthritis Who Were Inadequate Responders or Intolerant to DiseaseModifying Antirheumatic Drugs. Rheumatol Ther. 2019;6(3):339-352. doi: 10.1007/s40744019-0157-3.

Tanaka Y., Wada K., Takahashi Y., Hagino O., van Hoogstraten H., Graham N.M.H., Kameda H. Sarilumab plus methotrexate in patients with active rheumatoid arthritis and inadequate response to methotrexate: results of a randomized, placebo-controlled phase III trial in Japan. Arthritis Res Ther. 2019;21(1):79. doi: 10.1186/s13075-019-1856-4.

Genovese M.C., van Adelsberg J., Fan C., Graham N.M.H., van Hoogstraten H., et al. EXTEND study investigators. Two years of sarilumab in patients with rheumatoid arthritis and an inadequate response to MTX: safety, efficacy and radiographic outcomes. Rheumatology (Oxford). 2018;57(8):1423-1431. doi: 10.1093/rheumatology/key121.

Kameda H., Wada K., Takahashi Y., Hagino O., van Hoogstraten H., Graham N., Tanaka Y. Sarilumab monotherapy or in combination with non-methotrexate disease-modifying antirheumatic drugs in active rheumatoid arthritis: A Japan phase 3 trial (HARUKA). Mod Rheumatol. 2019:1-10. doi: 10.1080/14397595.2019.1639939.

Gossec L., Strand V., Proudfoot C., Chen C.I., Guillonneau S., Kimura T., van Hoogstraten H., Mangan E., Reaney M. Effects of Sarilumab on Rheumatoid Arthritis as Reported by Patients Using the Rheumatoid Arthritis Impact of Disease Scale. J Rheumatol. 2019;46(10):12591267. doi: 10.3899/jrheum.180904.

Choy E., Freemantle N., Proudfoot C., Chen C.I., Pollissard L., Kuznik A., et al. Evaluation of the efficacy and safety of sarilumab combination therapy in patients with rheumatoid arthritis with inadequate response to conventional disease-modifying antirheumatic drugs or tumour necrosis factor α inhibitors: systematic literature review and network meta-analyses. RMD Open. 2019;5(1):e000798. doi: 10.1136/ rmdopen-2018-000798.

Muszbek N., Proudfoot C., Fournier M., Chen C.I., Kuznik A., Kiss Z., Gal P., Michaud K. Economic Evaluation of Sarilumab in the Treatment of Adult Patients with Moderatelyto-Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Conven tional Synthetic Disease-Modifying Antirheumatic Drugs. Adv Ther. 2019;36(6):1337-1357. doi: 10.1007/s12325-019-00946-1.

Muszbek N., Proudfoot C., Fournier M., Chen C.I., Kuznik A., Kiss Z., Gal P., Michaud K. Economic Evaluation of Sarilumab in the Treatment of Adult Patients with Moderately-to-Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Conventional Synthetic Disease-Modifying Antirheumatic Drugs. Adv Ther. 2019;36(6):1337-1357. doi: 10.1007/s12325-019-00946-1.

Mahajan T.D., Mikuls T.R. Recent advances in the treatment of rheumatoid arthritis. Curr Opin Rheumatol. 2018;30(3):231-237. doi: 10.1097/BOR.0000000000000496.

Atzeni F., Nucera V., Masala I.F., Sarzi-Puttini P., Bonitta G. Il-6 Involvement In Pain, Fatigue And Mood Disorders In Rheumatoid Arthritis And The Effects Of Il-6 Inhibitor Sarilumab. Pharmacol Res. 2019;2019:104402. doi: 10.1016/j.phrs.2019.104402.

Pelechas E., Voulgari P.V., Drosos A.A. Clinical evaluation of the safety, efficacy and tolerability of sarilumab in the treatment of moderate to severe rheumatoid arthritis. Ther Clin Risk Manag. 2019;(15):1073-1079. doi: 10.2147/TCRM.S167452.

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