References

medsovet

Медицинский Совет

Meditsinskiy sovet = Medical Council

2079-701X2658-5790

REMEDIUM GROUP Ltd.

10.21518/2079-701X-2013-12-90-96

medsovet-1170

Research Article

РЕВМАТОЛОГИЯ

RHEUMATOLOGY

Ингибиторы киназ при ревматоидном артрите: реальность и перспективы

Kinase inhibitors in rheumatoid arthritis: reality and prospects

Каратеев

Д. Е.

Karateyev

D. Е.

noemail@neicon.ru

ФГБУ «НИИР им. В.А. Насоновой» РАМН, МоскваРоссияResearch Institute of Rheumatology named after V.A. Nasonova RAMS, MoscowRussian Federation

2013

30122013

0129096

2013

Каратеев Д.Е.

Karateyev D.Е.

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/1170

Статья посвящена возможностям применения ингибиторов тирозинкиназ в лечении ревматоидного артрита (РА). Представлен первый препарат из новой подгруппы таргетных синтетических базисных противовоспалительных препаратов - пероральный ингибитор янус-киназ тофацитиниб. Приводятся данные исследований ORAL START, ORAL SOLO и ORAL STEP по применению тофацитиниба у трех категорий пациентов: больные, ранее не получавшие метотрексат (МТ); пациенты, не ответившие на МТ и другие базисные противовоспалительные препараты (БПВП); пациенты, недостаточно ответившие на ингибиторы ФНО-альфа. Результаты исследований позволяют заключить, что тофацитиниб может назначаться как после неудач терапии БПВП и генно-инженерными биологическими препаратами, так и потенциально в качестве препарата 1-го ряда при РА. По мнению автора, тофацитиниб является весьма перспективным препаратом, который может стать важнейшим звеном стратегии активного лечения больных РА для достижения клинической ремиссии. Тем не менее необходимо проведение дальнейших исследований и накопление результатов практического применения препарата.

The article tells about the applicability of tyrosine kinase inhibitors in the treatment of rheumatoid arthritis (RA). The first drug from the new subgroup of targeted disease-modifying synthetic anti-inflammatory drugs is in focus - the oral inhibitor of Janus kinase Tofacitinib. There are results of ORAL START, ORAL SOLO and ORAL STEP studies which evaluated tofacitinib in three categories of patients: those who didn't undergo methotrexate (MTX) treatment in the past; patients without response to MT and other disease modifying anti-rheumatic drugs (DMARDs); patients with insufficient response to TNF-alpha inhibitors. The results show that Tofacitinib can be indicated either after failure of DMARD therapy and genetically engineered biologic drugs, or can be used as first-line therapy in RA. According to the author, Tofacitinib is a very promising medication which can become an essential element of the active treatment strategy for RA patients to achieve clinical remission. Nevertheless, further research is needed, as well as records of practical outcomes of the drug use.

ревматоидный артритбазисные противовоспалительные препаратыгенно-инженерные биологические препаратыингибиторы тирозинкиназытофаци-тинибrheumatoid arthritisdisease-modifying anti-inflammatory drugsgenetically engineered biologic drugstyrosine kinase inhibitorstofacitinib

References1

Emery P. Optimizing outcomes in patients with rheumatoid arthritis and an inadequate response to anti-TNF treatment. Rheumatology (Oxford). 2012;51(Suppl 5):22-30.

Tak PP. A personalized medicine approach to biologic treatment of rheumatoid arthritis: a preliminary treatment algorithm. Rheumatology (Oxford). 2012;51:600-9.

Moots RJ, Naisbett-Groet B. The efficacy of biologic agents in patients with rheumatoid arthritis and an inadequate response to tumour necrosis factor inhibitors: a systematic review. Rheumatology (Oxford). 2012 Dec;51(12):2252-61.

Simsek I. Predictors of response to TNF inhibitors in rheumatoid arthritis - do we have new tools for personalized medicine? Bull NYUHosp Jt Dis, 2012;70:187-90.

Большая советская энциклопедия. М.: Советская энциклопедия. 1969-1978.

Kyttaris V. Kinase inhibitors: a new class of antirheumatic drugs. Drug Design. Development and Therapy, 2012;6:245-250.

Riccaboni M, Bianchi I, Petrillo P. Spleen tyrosine kinases: biology, therapeutic targets and drugs. DrugDiscov Today. 2010;15:517-530. Park SR, Speranza G, Piekarz R, et al. A multi-histology trial of fostamatinib in patients with advanced colorectal, non-small cell lung, head and neck, thyroid, and renal cell carcinomas, and pheochromocytomas. Cancer Chemother Pharmacol., 2013;71:981-90.

Nijjar JS, Tindell A, Mclnnes IB, Siebert S. Inhibition of spleen tyrosine kinase in the treatment of rheumatoid arthritis. Rheumatology (Oxford). 2013;52:1556-62.

Genovese MC, Kavanaugh A, Weinblatt ME, et al. An oral Syk kinase inhibitor in the treatment of rheumatoid arthritis: a three-month randomized, placebo-controlled, phase II study in patients with active rheumatoid arthritis that did not respond to biologic agents. Arthritis Rheum. 2011;63:337-345.

Becker S, Groner B, Muller CW. Three-dimentional structure of the STAT3b homodimer bound to DNA. Nature, 1998;394:145-151.

Guschin D, Rogers N, Briscoe J, et al. A major role for the protein tyrosine kinase JAK1 in the JAK/STAT signal transduction pathway in response to interleukin-6. EMBO J. 1995;14:1421-9.

James C, Ugo V, Le Couedic JP, et al. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature 2005;434:1144-1148.

Okiyama N, Furumoto Y, Villarroel VA, et al. Reversal of CD8 T cell-Mediated Mucocutaneous Graft-Versus-Host-Like Disease by the JAK Inhibitor, Tofacitinib. J Invest Dermatol. 2013;8. doi: 10.1038/jid.2013.476. [Epub ahead of print].

Минеев В.Н., Сорокина Л.Н. Современные представления о JAK-STAT системе как новой сигнальной системе и ее нарушениях при иммунной патологии. Часть 1. Аллергология. 2005;4:38-44.

Feist E, Burmester G. Small molecules targeting JAKs-a new approach in the treatment of rheumatoid arthritis. Rheumatology 2013, 52:1352-1357.

Jones G, Sebba A, Gu J, et al. Comparison of tocilizumab monotherapy versus methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis: the AMBITION study. Ann Rheum Dis. 2010, 69:88-96.

Strand V, Fleischmann R, Alten RE., et al. Oral start: effects of the oral jak inhibitor tofacitinib monotherapy versus methotrexate on patient-reported outcomes in the phase 3 oral start trial of active rheumatoid arthritis. Ann Rheum Dis 2013;72(Suppl3):252, EULAR Congress abstr. THU0258.

Burmester GR, Blanco R., Charles-Schoerman C, et al. Tofacitinib (CP-690,550) in combination with methotrexate in patients with active rheumatoid arthritis with an inadequate response to tumour necrosis factor inhibitors: a randomised phase 3 trial. Lancet. 2013;9, 381(9865):451-60.

Smolen JS, Landewé R, Breedveld FC, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann Rheum Dis. 2013 Oct 25. doi: 10.1136/annrheumdis-2013-204573. [Epub ahead of print].

Salgado E, Maneiro JR, Carmona L, Gomez-Reino JJ. Safety profile of protein kinase inhibitors in rheumatoid arthritis: systematic review and meta-analysis. Ann Rheum Dis. 2013 Apr 18. [Epub ahead of print].

Fleischmann R, Kremer J, Cush J, et al. Placebo-controlled trial of tofacitinib monotherapy in rheumatoid arthritis. N Engl J Med. 2012 Aug 9;367(6):495-507.

Smolen JS, van der Heijde D, Machold KP, Aletaha D, Landewé R. Proposal for a new nomenclature of disease-modifying antirheumatic drugs. Ann Rheum Dis. 2013 Sep 26. doi: 10.1136/annrheumdis-2013-204317. [Epub ahead of print].

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