References

rsp

Научно-практическая ревматология

Rheumatology Science and Practice

1995-44841995-4492

IMA-PRESS, LLC

10.14412/1995-4484-2013-635

rsp-773

Research Article

Статьи

Articles

Опыт применения тоцилизумаба у больных ревматоидным артритом (по данным многоцентрового исследования ЛОРНЕТ)

Experience with tocilizumab in patients with rheumatoid arthritis (according to the data of the LORNET multicenter trial)

Панасюк

Е. Ю.

Panasyuk

E Yu

Amirdzhanova

V N

Amirdzhanova

V N

Avdeyeva

Anastasia Sergeyevna

Avdeyeva

Anastasia Sergeyevna

9056249400@mail.ru

Лучихина

Е. Л.

Luchikhina

E L

Александрова

Елена Николаевна

Aleksandrova

E N

Новиков

А. А.

Novikov

A A

Насонов

Евгений Львович

Nasonov

E L

2013

15042013

512

№2 (2013)

104110

2013

Панасюк Е.Ю., Amirdzhanova V.N., Avdeyeva A.S., Лучихина Е.Л., Александрова Е.Н., Новиков А.А., Насонов Е.Л.

Panasyuk E.Y., Amirdzhanova V.N., Avdeyeva A.S., Luchikhina E.L., Aleksandrova E.N., Novikov A.A., Nasonov 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://rsp.mediar-press.net/rsp/article/view/773

Цель оценить изменение качества жизни пациентов с ревматоидным артритом (РА) при добавлении к терапии базисными противовоспалительными препаратами (БПВП) тоцилизумаба (ТЦЗ), а также изучить эффективность и безопасность терапии ТЦЗ у больных РА с неадекватным ответом на предшествующее лечение БПВП. Материал и методы. Обследован 201 больной РА. Все пациенты получили по шесть инфузий ТЦЗ в дозе 8 мг/кг внутривенно с интервалом в 4 нед на фоне стабильной терапии БПВП и глюкокортикоидами. Для оценки эффективности терапии ТЦЗ использовали критерии EULAR, ACR, а также индексы активности SDAI и CDAI. Ремиссию заболевания оценивали по критериям EULAR. Результаты и обсуждение. До начала терапии ТЦЗ значения (медиана [25-й; 75-й перцентили]) индексов DAS28 6,8 [6,1; 7,4], SDAI 41,8 [34,6; 53,7] и CDAI 39,2 [31,4; 49,5] соответствовали высокой активности РА. К 4-й неделе терапии ТЦЗ отмечено снижение уровней DAS28 4,6 [3,8; 5,4], SDAI 24,6 [17,8; 33,4] и CDAI 23,6 [17,5; 32,0], сохранявшееся до 24-й недели (р<0,01). К 24-й неделе терапии ТЦЗ у 133 (70,4%) больных наблюдался хороший эффект по критериям EULAR, у 54 (28,6%) пациентов удовлетворительный; эффект отсутствовал у 2 (1,1%) больных. Эффект по ACR20/50/70 регистрировался соответственно у 89,1/70,6/44,3% больных. Ремиссия по критериям EULAR была достигнута у 51,3% больных, по индексу SDAI у 21,4%. Наблюдалось улучшение функционального состояния, а также качества жизни по опросникам EQ-5D и SF-36. Нормализация уровня С-реактивного белка и СОЭ регистрировалась через 4 нед после первой инфузии препарата и сохранялась до 24-й недели лечения. Заключение. Таким образом, анализ данных российского исследования убедительно свидетельствует об эффективности и хорошей переносимости ТЦЗ при тяжелом РА, резистентном к стандартной терапии БПВП.

Objective: to estimate quality of life changes in patients with rheumatoid arthritis (RA) while adding tocilizumab (TCZ) to therapy with disease-modifying antirheumatic drugs (DMARDs) and to study the efficiency and safety of the therapy in RA patients with an inadequate response to previous DMARD treatment. Subjects and methods. 201 patients with RA were examined. All the patients received six intravenous infusions of TCZ 8 mg/kg at a 4-week interval during stable therapy with DMARDs and glucocorticoids. The EULAR/ACR classification criteria and SDAI and CDAI were used to evaluate the efficiency of TCZ therapy. Remission was assessed by the EULAR criteria. Results and discussion. Prior to TCZ therapy, median [25th to 75th percentiles] DAS28 6.8 [6.1 to 7.4], SDAI 41.8 [34.6 to 53.7], and CDAI 39.2 [31.4 to 49.5] corresponded to high RA activity. At week 4 of TCZ therapy, there was a reduction in DAS28 (4.6 [3.8 to 5.4]), SDAI (24.6 [17.8 to 33.4]), and CDAI (23.6 [17.5 to 32.0]), which was retained until 24 weeks (р < 0.01). At week 24 of TCZ therapy, good and fair effects according to the EULAR criteria were observed in 133 (70.4%) and 54 (28.6%) patients, respectively; no effect was seen in 2 (1.1%) patients. The ACR20/50/70 effect was recorded in 89.1, 70.6, and 44.3% of the patients, respectively. EULAR and SDAI remissions were achieved in 51.3 and 21.4%, respectively. There were improvements in functional status and quality of life according to the EQ-5D and SF-36 questionnaires. C-reactive protein levels and erythrocyte sedimentation rate normalized 4 weeks after the first infusion of the drug and remained until week 24 of treatment. Conclusion. Thus, an analysis of the data of the Russian trial convincingly suggests that TCZ is effective and well tolerated in severe RA resistant to standard therapy with DMARDs.

ревматоидный артриттоцилизумабкачество жизниремиссия заболевания

DAS28SDAIrheumatoid arthritistocilizumabquality of lifeDAS28SDAIremission

References1

<div>Амирджанова В.Н. Популяционные показатели качества жизни. Науч-практич ревматол 2008;1:36-48.Насонов Е.Л. Новые подходы к фармакотерапии ревматоидного артрита: перспективы применения тоцилизумаба (моноклональные антитела к рецептору интерлейкина-6). Тер арх 2010;5:64-71.Firestein G.S. Evolving concepts of rheumatoid arthritis. Nature 2003;423:356-61.Fonseca J.E., Santos M.J., Canhao H., Choy E. Interleukin-6 as a key player in systemic inflammation and joint destruction. Autoimmun Rev 2009;8:538-42.Assier E., Boissier M., Dayer J. Interleukin-6: from identification of the cytokine to development of targeted treatments. Joint Bone Spine 2010;77:532-6.Gabay C., Kushner I. Acute-phase proteins and other systemic responses to inflammation. Acute-phase proteins and other systemic responses to inflammation. N Engl J Med 1999;340:448-54.Romano M., Polentarutti N., Fruscella P. et al. Role of IL-6 and its soluble receptor in induction of chemokines and leukocyte recruitment. Immunity 1997;6;315—25.Lally F., Smith E., Filer A. et al. A novel mechanism of neutrophil recruitment in a coculture model of the rheumatoid synovium. Arthr Rheum 2005;52:3460-9.Smolen J.S., Aletaha D., Koeller M. et al. New therapies for treatment of rheumatoid arthritis. Lancet 2007;370:1861-74.Paleolog E.M. Angiogenesis in rheumatoid arthritis. Arthr Res 2002;4(Suppl 3):81-90.Schett G. Cells of the synovium in rheumatoid arthritis. Osteoclasts. Arthr Res Ther 2007;9:203.Kudo O., Sabokbar A., Pocock A. et al. Interleukin-6 and interleukin-11 support human osteoclast formation by a RANKL-independent mechanism. Bone 2003;32:1-7.Nakahara H., Song J., Sugimoto M. et al. Anti-interleukin-6 receptor antibody therapy reduces vascular endothelial growth factor production in rheumatoid arthritis. Arthr Rheum 2003;48:1521-9.Dayer J.M., Choy E. Therapeutic targets in rheumatoid arthritis: the interleukin-6 receptor. Rheumatology (Oxford) 2010;49:15-24.Bettelli E., Carrier Y., Gao W. et al. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 2006;441:235-8.Naka T., Nishimoto N., Kishimoto T. The paradigm of IL-6: from basic science to medicine. Arthr Res 2002;4(Suppl 3):233-42.Heinrich P.C., Behrmann I., Haan S. et al. Principles of interleukin (IL)-6-type cytokine signalling and its regulation. Biochem J 2003;374(Pt 1):1-20.Rose-John S., Scheller J., Elson G., Jones S.A. Interleukin-6 biology is coordinated by membrane-bound and soluble receptors: role in inflammation and cancer. J Leukoc Biol 2006;80:227-36.Jones S.A., Richards PJ., Scheller J., Rose-John S. IL-6 transsignaling: the in vivo consequences. J Interferon Cytokine Res 2005;25:241-53.Houssiau F.A., Devogelaer J.P., van Damme J. et al. Interleukin-6 in synovial fluid and serum of patients with rheumatoid arthritis and other inflammatory arthritides. Arthr Rheum 1988;31:784-8.Kotake S., Sato K., Kim K.J. et al. 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;11:88-95.Sack U., Kinne R.W., Marx T. et al. Interleukin-6 in synovial fluid is closely associated with chronic synovitis in rheumatoid arthritis. Rheumatol Int 1993;13:45-51.Smolen J.S., Beaulieu A., Rubbert-Roth A. et al. Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebocontrolled, randomised trial. Lancet 2008;371:987-97.Genovese M.C., McKay J.D., Nasonov E.L. et al. Interleukin-6 receptor inhibition with tocilizumab reduces disease activity in rheumatoid arthritis with inadequate response to disease-modifying antirheumatic drugs: the tocilizumab in combination with traditional disease-modifying antirheumatic drug therapy study. Arthr Rheum 2008;58:2968-80.Emery P., Keystone E., Tony H. et al. IL-6 receptor inhibition with tocilizumab improves treatment outcomes in patients with rheumatoid arthritis refractory to anti-TNF biologics: results from a 24-week multicentre randomised placebo-controlled trial. Ann Rheum Dis 2008;67:1516-23.Nishimoto N., Hashimoto J., Miyasaka N. et al. Study of active controlled monotherapy used for rheumatoid arthritis, an IL-6 inhibitor (SAMURAI): evidence of clinical and radiographic benefit from an X ray reader-blinded randomised controlled trial of tocilizumab. Ann Rheum Dis 2007;66:1162-7.Burmester G., Feis E., Kellner H. et al. Effectiveness and safety of Ше interleukin 6-receptor antagonist tocilizumab after 4 and 24 weeks in patients with active rheumatoid arthritis: the first phase IIIb real-life study (TAMARA). Ann Rheum Dis 2011;70:755-9.Sibilia J., Graninger W., Ostor A. et al. Comparison of tocilizumab as monotherapy or with add-on DMARDS in patients with rheumatoid arthritis and an inadequate response to previous treatments: ACT-SURE results. Ann Rheum Dis 2011;70(Suppl 3):466.Patel A., Moreland L. Interleukin-6 inhibition for treatment of rheumatoid arthritis: a review of tocilizumab therapy. Drug Des Devel Ther 2010;4:263-78.Fransen J., Stucki G., van Reil P.L.C.M. Rheumatoid arthritis measures. Arthr Rheum 2003;49:214-24.Felson D., Anderson J., Lange M. et al. Should improvement in rheumatoid arthritis clinical trials be defined as fifty percent or seventy percent improvement in core set measures, rather than twenty percent? Arthr Rheum 1998;41:1564-70.Smolen J., Breedveld F., Schiff M. et al. A simplified disease activity index for rheumatoid arthritis for use in clinical practice. Rheumatology 2003;42:244-57.Aletaha D., Nell V., Stamm T. et al. Acute phase reactants add little to composite disease activity indices for rheumatoid arthritis: validation of a clinical activity score. Arthr Res Ther 2005;7:796-806.Choy E., Isenberg D.A., Garrood T. et al. Therapeutic benefit after blocking interleukin-6 activity in rheumatoid arthritis with an anti-interleukin 6 receptor monoclonal antibody. Arthr Rheum 2002;46:3143-50.Nishimoto N., Yoshizaka K., Miaysaka N. et al. Treatment of rheumatoid arthritis with humanized anti-interleukin-6 receptor antibody: a multicenter, double-blind, placebo-controlled trial. Arthr Rheum 2004;50:1761-9.Kremer J., Blanco R., Brzosko M. et al. Tocilizumab inhibits structural joint damage in rheumatoid arthritis patients with inadequate responses to methotrexate: Results from the double-blind treatment phase of a randomized placebo-controlled trial of tocilizumab safety and prevention of structural joint damage at one year. Arthr Rheum 2011;63:609-21.Leffers H., Ostergaard M., Glintborg B. Rheumatoid arthritis patients treated in routine care efficacy of abatacept and tocilizumab based on data from the nationwide Danish DANBIO registry. Ann Rheum Dis 2011;70(Suppl 3):463.Yoshida K., Kishimoto M., Tokuda Y. Tocilizumab vs TNF inhibitors: difference in the quality of remission. Ann Rheum Dis 2011;70(Suppl 3):470.Yazici Y., Curtis J., Ince A. et al. Efficacy of tocilizumab in patients with moderate to severe active rheumatoid arthritis and a previous inadequate response to disease-modifying antirheumatic drugs: the ROSE study. Ann Rheum Dis 2012;71:198-205.Iking-Konert C., Aringer M., Wollenhaupt J. et al. Performance of the new 2011 ACR/EULAR remission criteria with tocilizumab using the phase IIIb study TAMARA as an example and their comparison with traditional remission criteria. Ann Rheum Dis 2011;70:1986-90.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.Maini P., Taylor P., Szechinski J. et al. Double-blind randomized controlled clinical trial of the interleukin-6 receptor antagonist, tocilizumab, in european patients with rheumatoid arthritis who had an incomplete response to methotrexate. Arthr Rheum 2006;54:2817-29.Emery P., Keystone E., Tony H.-P. IL-6 Receptor inhibition with tocilizumab improves arthritis refractory to anti-TNF biologics: results treatment outcomes in patients with rheumatoid from a 24-week multicentre randomised placebo controlled trial. Ann Rheum Dis 2008;67:1516-23.Nishimoto N., Miyasaka N., Yamamoto K. et al. Study of active controlled tocilizumab monotherapy for rheumatoid arthritis patients with an inadequate response to methotrexate (SATORI): significant reduction in disease activity and serum vascular endothelial growth factor by IL-6 receptor inhibition therapy. Mod Rheumatol 2009;19:12-9.BykerkV., Ostor A., Alvaro-Gracia J. et al. Tocilizumab in patients with active rheumatoid arthritis and an inadequate response to DMARDs and/or the TNF inhibitor therapy: a large open-label study close to clinical precice. Ann Rheum Dis 2012;71:1950-4.Dougados M., Kissel K., Sheeran T. et al. Adding tocilizumab or switching to tociluzumab monotherapy in methotrexate inadequate responders: 24-week symtomatic and structural results od a 2-year randomized controlled strategy trial in rheumatoid arthritis (ACT-RAY). Ann Rheum Dis 2013;72:43-50.Weinblatt E., Kremer J.M., Cush J.J. et al. Tocilizumab monotherapy and tocilizumab plus disease-modifying antirheumatic drugs in a US rheumatoid arthritis population with inadequate response to anti-tumor necrosis factor agents. Arthr Rheum 2011;63(Suppl):162.</div>

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