rspНаучно-практическая ревматологияRheumatology Science and Practice1995-44841995-4492IMA-PRESS, LLC10.14412/1995-4484-2010-1162rsp-1076Research ArticleСтатьиArticlesВЛИЯНИЕ РИТУКСИМАБА НА СИСТЕМУ ТРАНСПОРТАХОЛЕСТЕРИНА КРОВИ У БОЛЬНЫХ РЕВМАТОИДНЫМАРТРИТОМEFFECT OF RITUXIMAB ON THE BLOOD CHOLESTEROL TRANSPORT SYSTEM IN PATIENTSWITH RHEUMATOID ARTHRITISПопковаТ. В.PopkovaTatyana Valentinovnapopkovatv@mail.ruНовиковаД. С.NovikovaD S-LinevaO GLinevaO G-НовиковА. А.NovikovA A-АлександроваЕлена НиколаевнаAleksandrovaE N-НасоновЕвгений ЛьвовичNasonovE L-201015082010484№4 (2010)2631Copyright © Попкова Т.В., Новикова Д.С., Lineva O.G., Новиков А.А., Александрова Е.Н., Насонов Е.Л., 20102010Попкова Т.В., Новикова Д.С., Lineva O.G., Новиков А.А., Александрова Е.Н., Насонов Е.Л.Popkova T.V., Novikova D.S., Lineva O.G., Novikov A.A., Aleksandrova E.N., 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/1076

Цель. Изучить динамику показателей липидного спектра крови у больных ревматоидным артритом (РА) на фоне лечения ри- туксимабом в течение 24-недельного наблюдения. Материал и методы. В исследование включено 39 больных (36 женщин и 3 мужчины) с достоверным диагнозом РА, средний воз- раст 50 лет, длительность заболевания 93,5 мес, активность по DAS - 6,1 балла. У 6 больных в анамнезе выявлена неэффек- тивность метотрексата, у 30 - двух и более базовых противовоспалительных препаратов (БПВП), у 14 из 39 - неэффектив- ность терапии ингибиторами ФНО ƒ. Липидный спектр крови и толщину комплекса интима-медиа (КИМ) определяли до на- чала лечения ритуксимабом и через 24 нед после первого его введения. Препарат вводили внутривенно капельно по 1000 мг дву- кратно с интервалом в 14 дней. Эффективность лечения оценивали по индексу активности РА - DAS 28. Все пациенты отве- тили на терапию ритуксимабом (удовлетворительный/хороший эффект). Результаты. Отмечено двукратное снижение частоты гипоальфалипопротеинемии и повышенного индекса атерогенности. Повышенные уровни холестерина (ХС), триглицеридов (ТГ), ХС липопротеидов низкой плотности (ЛНП) встречались с одина- ковой частотой до и через 24 нед после начала введения ритуксимаба. Выявлено увеличение концентрации ХС на 5% и значи- тельное повышение уровня ХС липопротеидов высокой плотности (ЛВП) - на 22%, снижение индекса атерогенности на 18,6% (р<0,05 во всех случаях). Обнаружена тенденция к нарастанию уровня ХС ЛНП и ТГ, однако различия не достигли статисти- ческой значимости. Изменение спектра липидов и липопротеидов крови ассоциировалось с выраженным снижением активно- сти заболевания - уменьшением концентрации С-реактивного белка (СРБ), СОЭ, IgM ревматоидного фактора (РФ), индекса DAS 28, улучшением функционального статуса больного (индекс HAQ) (р<0,05). Отмечено достоверное снижение максималь- ной толщины КИМ сонных артерий у пациентов с РА: до лечения ритуксимабом она составила 1,09 (0,94-1,2) мм, через 24 нед введения препарата - 0,95 (0,8-1,3) мм (р=0,001).

Objective: To study the time course of changes in the indices of the blood lipid spectrum in patients with rheumatoid arthritis (RA) treated with rituximab during a 24-week follow-up. Subjects and methods. The study enrolled 39 patients (36 females and 3 males) with a valid diagnosis of RA; their mean age was 50 years; disease duration 93.5 months; duration activity scale (DAS) 6.1 scores. A previous ineffective treatment with methotrexate was found in 6 patients; that with two basic anti-inflammatory drugs or more in 30, and previous TNF-ƒ inhibitor therapy failed in 14 of the 39 patients. The blood lipid spectrum and intima-media thickness (IMT) were determined before and 24 weeks after the first injection of rituximab. The drug was intravenously administered dropwise in a dose of 1000 mg twice at a 14-week interval. Therapeutic efficiency was estimated according to the RA activity index - DAS28. All the patients showed a satisfactory/good response to rituximab therapy. Results. There was a double reduction in the frequency of hypoalfalipoproteinemia and in the increased atherogenicity index (AI). Elevated cholesterol (CH), triglycerides (TG), and low-density lipoprotein (LDL CH) levels were found in equal frequencies before and 24 week after rituximab administration. There was a 5% rise in CH concentrations, a considerable (22%) increase in high-density lipoprotein CH, and an 18.6% decrease in AI (p<0.05 in all cases). The levels of LDL CH and TG tended to increase; however, they failed to achieve statistical significance. The change in the spectrum of lipids and blood lipoproteins was associated with the pronounced decline in disease activity (decreases in C-reactive protein concentrations, erythrocyte sedimentation rate, IgM rheumatoid factor, and DAS28 index) and better patient functional status (Health Assessment Questionnaire (HAQ) index) (p<0.05). There was a significant reduction in the maximum carotid IMT in patients with RA: it was 1.09 (0.94-1.2) and 0.95 (0.8-1.3) mm before and 24 weeks after rituximab administration, respectively (p=0.001).

ревматоидный артритхроническое воспалениелипидный спектр кровиритуксимабrheumatoid arthritischronic inflammationblood lipid spectrumrituximabReferences<div><p>Попкова Т.В., Новикова Д.С., Насонов Е.Л. Атеросклероз при ревматических заболеваниях. В кн.: Ревматология: клинические рекомендации. M.: ГЭОТАР-Медиа, 2010;678-702.</p><p>Peters M.J., Symmons D.P., McCarey D.W. et al. EULAR evidence-based recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other types of inflammatory arthritis - TASK FORCE Cardiovascular risk management in RA. Ann Rheum Dis 2010;69(2):325-31.</p><p>Meune C., Touze E., Trinqurte L. et al. Trends in cardiovascular mortality in patients with rheumatoid arthritis over 50 years: a systematic review and meta-analisis of cohort studies. Rheumatology 2009;48(10):1309-13.</p><p>Van Halm V.P., Peters V.P., Voskuyl M.J. et al. Rheumatoid arthritis versus type 2 diabetes as a risk factor for cardiovascular disease: a cross-sectional study. Ann Rheum Dis 2009;68:1395-400.</p><p>Kremers H.M., Crowson C.S., Therneau T.M. et al. High ten-year risk of cardiovascular disease in newly diagnosed rheumatoid arthritis patients. A population-based cohort study. Arthr Rheum 2008;58(8):2268-74.</p><p>Goodson N.I., Willes N.J., Lunt N.C. Mortality on early inflammatory arthritis: cardiovascular mortality in seropositive patients. Arhtr Rheum 2002;46:2010-9.</p><p>Gonzalez-Gay M.A., Gonzalez-Juanatey C., Martin J. Rheumatoid arthritis: a disease associated with accelerated atherogenesis. Semin Arthr Rheum 2005;35:8-17.</p><p>Gerli R., Bocci E.B., Sherer Y. et al. Association of anti-cyclic citrullinated peptide antibodies with subclinical atherosclerosis in patients with rheumatoid arthritis. Ann Rheum Dis 2008;67:724-5.</p><p>Lopez-Longo F.J., Oliver-Minarro D., de la Torre I. et al. Association between anticyclic citrullinated peptide antibodies and ischemic heart disease in patients with rheumatoid arthritis. Arthr Rheum 2009;61:419-24.</p><p>Nurmohamed M., Dijkmans B. Dyslipidemia, statins and rheumatoid arthritis. Ann Rheum Dis 2009;68:453-5.</p><p>Gazi I.F., Boumpas D.T., Mikhailidis D.P. et al. Clustering of cardiovascular risk factors in rheumatoid arthritis: the rationale for using statins. Clin Exp Rheumatol 2007;25:102-11.</p><p>Попкова Т.В., Новикова Д.С., Новиков А.А. и др. Роль нарушений в системе транспорта холестерина крови в развитии атеросклероза при ревматоидном артрите. Науч-практич ревматол 2007;5:4-10.</p><p>Bisoendial R., Stroes E., Kastelein J. et al. Targeting cardiovascular risk in rheumatoid arthritis: a dual role for statins. Nat Rev Rheumatol 2010; doi:10.1038/nrrheum.2009,277.</p><p>Del Rincon I., Williams K., Stern M.P. et al. High incidence of cardiovascular events in a rheumatoid arthritis cohort not explained by traditional cardiac risk factors. Arthr Rheum 2001;44:2737-45.</p><p>Dessein P.H., Joffe B.I., Veller M.G. et al. Traditional and nontraditional cardiovascular risk factors are associated with atherosclerosis in rheumatoid arthritis. J Rheumatol 2005;32:435-42.</p><p>Choi E., Sattar N. Interpreting lipid levels in the context of high-grade inflammatory states with a focus on rheumatoid arthritis: a challenge to conventional cardiovascular risk actions. Ann Rheum Dis 2009;68:460-9.</p><p>Насонов Е. Л. Применение ритуксимаба при ревматоидном артрите. Ритуксимаб (Мабтера) в лечении ревматических заболеваний (международный и российский опыт). Науч-практич ревматол 2009;1(прил.):3-22.</p><p>Ревматология. Нац. руководство. Под ред. Е.Л. Насонова, В.А. Насоновой. М.: ГЭОТАР-Медиа, 2008.</p><p>Kerekes G., Soltesz P., Der H. Effects of rituximab treatment on endothelial dysfunction, carotid atherosclerosis, and lipid profile in rheumatoid arthritis. Clin Rheumatol 2009;28:705-10.</p><p>Gonzalez-Juanatey C., Llorca J., Vazques-Rodrigez T.R. et al. Short-term improvement of endothelial function in rituximab- treated rheumatoid arthritis patients refractory to tumor necrosis factor-alfa blocker therapy. Arthr Rheum 2008;59:1821-4.</p><p>Kerekes G., Soltesz P., Der H. et al. Effects of biologics on vascular function and atherosclerosis associated with rheumatoid arthritis. Ann NY Acad Sci 2009;1173:814-21.</p><p>Arnett F.C., Edworthy S.M., Bloch D.A. The ARA 1987 revised criteria for classification of rheumatoid arthritis. Arthr Rheum 1988;31:315-24.</p><p>Кардиология. Нац. руководство. Подред. Ю.Н. Беленкова, Р.Г. Оганова. М.: ГЭОТАР-Медиа, 2007;1232 с.</p><p>Олюнин Ю.А. Оценка активности и эффективности терапии ревматоидного артрита. Международные индексы оценки активности, функционального статуса и качества жизни больных ревматическими заболеваниями. М.: Изд. группа Ассоциации ревматологов России, 2007;3-12.</p><p>Haward G., Sharrett A.R., Heiss G. et al. Carotid artery intima-media thickness distribution in general populations as evaluated by B-mode ultrasound. Stroke 1993;24:1297-304.</p><p>Artiss J.D., Zak B. Measurement of cholesterol concentration. In: Rifai N., Warmic G.R., Dominiczak M.H., eds. Handbook of lipoprotein testing. Washington: AACC Press, 1997;99-114.</p><p>Friedwald W.T., Levy R.J., Fredrickson D.S. Estimation of the calculation of LDL cholesterol in plasma without use of the preparative ultracentrifuge. Clin Chem 1972;18:499-502.</p><p>Российские рекомендации по диагно- стике и коррекции нарушений липидного обмена с целью профилактики и лечения атеросклероза. В кн.: Национальные клинические рекомендации. Сборник. Под. ред. Р.Г. Оганова. 2-е изд. М.: Силицея-Полиграф, 2009;20-106.</p><p>Van Halm V.P., Nielen M.J., Nurmohamed M.T. et al. Lipids and inflammation: serial measurements of the lipid profile of blood donors who later developed rheumatoid arthritis. Ann Rheum Dis 2007;66:184-8.</p><p>Nielen M.J., van Halm V.P., Nurmohamed M.T. et al. Rheumatoid arthritis is preceded by a preclinical phase, characterized by increased C-reactive protein levels and a more atherogenic lipid profile. Arthr Rheum 2003;48:344.</p><p>Sattar N., Crompton P., Cherry L. Effects of tumor necrosis factor blockade on cardiovascular risk factors in psoriatic arthritis: a double-blind, placebo-controlled study. Arthr Rheum 2007;56:831-9.</p><p>Khovidhunkit W., Memon R.A.,Feingold K.R. et al. Infection and inflammation- induced proatherogenic changes of lipoproteins. J Infect Dis 2000;181(Suppl. 3):462-72.</p><p>Burger D., Dayer J.M. High-density lipoprotein-associated apolipoprotein A-1: the missing link between infection and chronic inflammation? Autoimmun Rev 2002;1:111-7.</p><p>Navab M., Berliner J.A.,Subbanagounder G. et al. HDL and inflammatory response induced by LDL-derived oxidized phospholipids. Arteriol Thromb Vasc Biol 2001;21:481-8.</p><p>McMahon M., Grossman J., FitzGerald J. Proinflammatory high-density lipoprotein as a biomarker for atherosclerosis in patients with systemic lupus erythematosus and rheumatoid arthritis. Arthr Rheum 2006;54(8):2541-9.</p><p>Ananth L., Prete P.E., Kashyap M.L. Apolipoproteins A-I and B and cholesterol in synovial fluid of patients with rheumatoid arthritis. Metabolism 1993;42(7):803-6.</p><p>Woods A., Brull D.J., Humphries S.E. et al. Genetics of inflammation and risk of coronary artery disease: the central role of interleukin-6. Eur Heart J 2000;21:1574-83.</p><p>Popa C., Netea M.G., Radstake T.R. et al. Markers of inflammation are negatively correlated with serum leptin in rheumatoid arthritis. Ann Rheum Dis 2005;64:303-5.</p><p>Nashimoto N., Yoshizaki K., Miyasaka 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.</p><p>Sattar N. Effect of tocilizumab treatment on lipid parameters (pooled data: OPTION &amp; TOWARD). Roche (data on file)</p><p>Maini R.N., Taylor P.C., 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.</p><p>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 randomized controlled trial of tocilizumab. Ann Rheum Dis 2007;66:1162-7.</p><p>Schimmel E.K., Yazici Y. Increased lipid levels but unchanged atherogenic index in rheumatoid artritis patients treated with biologic disease modifying antirheumatic drugs: published experience. Clin Exp Rheumatol 2009;27:446-51.</p></div><br /><div><p>Попкова Т.В., Новикова Д.С., Насонов Е.Л. Атеросклероз при ревматических заболеваниях. В кн.: Ревматология: клинические рекомендации. M.: ГЭОТАР-Медиа, 2010;678-702.</p><p>Peters M.J., Symmons D.P., McCarey D.W. et al. EULAR evidence-based recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other types of inflammatory arthritis - TASK FORCE Cardiovascular risk management in RA. Ann Rheum Dis 2010;69(2):325-31.</p><p>Meune C., Touze E., Trinqurte L. et al. Trends in cardiovascular mortality in patients with rheumatoid arthritis over 50 years: a systematic review and meta-analisis of cohort studies. Rheumatology 2009;48(10):1309-13.</p><p>Van Halm V.P., Peters V.P., Voskuyl M.J. et al. Rheumatoid arthritis versus type 2 diabetes as a risk factor for cardiovascular disease: a cross-sectional study. Ann Rheum Dis 2009;68:1395-400.</p><p>Kremers H.M., Crowson C.S., Therneau T.M. et al. High ten-year risk of cardiovascular disease in newly diagnosed rheumatoid arthritis patients. A population-based cohort study. Arthr Rheum 2008;58(8):2268-74.</p><p>Goodson N.I., Willes N.J., Lunt N.C. Mortality on early inflammatory arthritis: cardiovascular mortality in seropositive patients. Arhtr Rheum 2002;46:2010-9.</p><p>Gonzalez-Gay M.A., Gonzalez-Juanatey C., Martin J. Rheumatoid arthritis: a disease associated with accelerated atherogenesis. Semin Arthr Rheum 2005;35:8-17.</p><p>Gerli R., Bocci E.B., Sherer Y. et al. Association of anti-cyclic citrullinated peptide antibodies with subclinical atherosclerosis in patients with rheumatoid arthritis. Ann Rheum Dis 2008;67:724-5.</p><p>Lopez-Longo F.J., Oliver-Minarro D., de la Torre I. et al. Association between anticyclic citrullinated peptide antibodies and ischemic heart disease in patients with rheumatoid arthritis. Arthr Rheum 2009;61:419-24.</p><p>Nurmohamed M., Dijkmans B. Dyslipidemia, statins and rheumatoid arthritis. Ann Rheum Dis 2009;68:453-5.</p><p>Gazi I.F., Boumpas D.T., Mikhailidis D.P. et al. Clustering of cardiovascular risk factors in rheumatoid arthritis: the rationale for using statins. Clin Exp Rheumatol 2007;25:102-11.</p><p>Попкова Т.В., Новикова Д.С., Новиков А.А. и др. Роль нарушений в системе транспорта холестерина крови в развитии атеросклероза при ревматоидном артрите. Науч-практич ревматол 2007;5:4-10.</p><p>Bisoendial R., Stroes E., Kastelein J. et al. Targeting cardiovascular risk in rheumatoid arthritis: a dual role for statins. Nat Rev Rheumatol 2010; doi:10.1038/nrrheum.2009,277.</p><p>Del Rincon I., Williams K., Stern M.P. et al. High incidence of cardiovascular events in a rheumatoid arthritis cohort not explained by traditional cardiac risk factors. Arthr Rheum 2001;44:2737-45.</p><p>Dessein P.H., Joffe B.I., Veller M.G. et al. Traditional and nontraditional cardiovascular risk factors are associated with atherosclerosis in rheumatoid arthritis. J Rheumatol 2005;32:435-42.</p><p>Choi E., Sattar N. Interpreting lipid levels in the context of high-grade inflammatory states with a focus on rheumatoid arthritis: a challenge to conventional cardiovascular risk actions. Ann Rheum Dis 2009;68:460-9.</p><p>Насонов Е. Л. Применение ритуксимаба при ревматоидном артрите. Ритуксимаб (Мабтера) в лечении ревматических заболеваний (международный и российский опыт). Науч-практич ревматол 2009;1(прил.):3-22.</p><p>Ревматология. Нац. руководство. Под ред. Е.Л. Насонова, В.А. Насоновой. М.: ГЭОТАР-Медиа, 2008.</p><p>Kerekes G., Soltesz P., Der H. Effects of rituximab treatment on endothelial dysfunction, carotid atherosclerosis, and lipid profile in rheumatoid arthritis. Clin Rheumatol 2009;28:705-10.</p><p>Gonzalez-Juanatey C., Llorca J., Vazques-Rodrigez T.R. et al. Short-term improvement of endothelial function in rituximab- treated rheumatoid arthritis patients refractory to tumor necrosis factor-alfa blocker therapy. Arthr Rheum 2008;59:1821-4.</p><p>Kerekes G., Soltesz P., Der H. et al. Effects of biologics on vascular function and atherosclerosis associated with rheumatoid arthritis. Ann NY Acad Sci 2009;1173:814-21.</p><p>Arnett F.C., Edworthy S.M., Bloch D.A. The ARA 1987 revised criteria for classification of rheumatoid arthritis. Arthr Rheum 1988;31:315-24.</p><p>Кардиология. Нац. руководство. Подред. Ю.Н. Беленкова, Р.Г. Оганова. М.: ГЭОТАР-Медиа, 2007;1232 с.</p><p>Олюнин Ю.А. Оценка активности и эффективности терапии ревматоидного артрита. Международные индексы оценки активности, функционального статуса и качества жизни больных ревматическими заболеваниями. М.: Изд. группа Ассоциации ревматологов России, 2007;3-12.</p><p>Haward G., Sharrett A.R., Heiss G. et al. Carotid artery intima-media thickness distribution in general populations as evaluated by B-mode ultrasound. Stroke 1993;24:1297-304.</p><p>Artiss J.D., Zak B. Measurement of cholesterol concentration. In: Rifai N., Warmic G.R., Dominiczak M.H., eds. Handbook of lipoprotein testing. Washington: AACC Press, 1997;99-114.</p><p>Friedwald W.T., Levy R.J., Fredrickson D.S. Estimation of the calculation of LDL cholesterol in plasma without use of the preparative ultracentrifuge. Clin Chem 1972;18:499-502.</p><p>Российские рекомендации по диагно- стике и коррекции нарушений липидного обмена с целью профилактики и лечения атеросклероза. В кн.: Национальные клинические рекомендации. Сборник. Под. ред. Р.Г. Оганова. 2-е изд. М.: Силицея-Полиграф, 2009;20-106.</p><p>Van Halm V.P., Nielen M.J., Nurmohamed M.T. et al. Lipids and inflammation: serial measurements of the lipid profile of blood donors who later developed rheumatoid arthritis. Ann Rheum Dis 2007;66:184-8.</p><p>Nielen M.J., van Halm V.P., Nurmohamed M.T. et al. Rheumatoid arthritis is preceded by a preclinical phase, characterized by increased C-reactive protein levels and a more atherogenic lipid profile. Arthr Rheum 2003;48:344.</p><p>Sattar N., Crompton P., Cherry L. Effects of tumor necrosis factor blockade on cardiovascular risk factors in psoriatic arthritis: a double-blind, placebo-controlled study. Arthr Rheum 2007;56:831-9.</p><p>Khovidhunkit W., Memon R.A.,Feingold K.R. et al. Infection and inflammation- induced proatherogenic changes of lipoproteins. J Infect Dis 2000;181(Suppl. 3):462-72.</p><p>Burger D., Dayer J.M. High-density lipoprotein-associated apolipoprotein A-1: the missing link between infection and chronic inflammation? Autoimmun Rev 2002;1:111-7.</p><p>Navab M., Berliner J.A.,Subbanagounder G. et al. HDL and inflammatory response induced by LDL-derived oxidized phospholipids. Arteriol Thromb Vasc Biol 2001;21:481-8.</p><p>McMahon M., Grossman J., FitzGerald J. Proinflammatory high-density lipoprotein as a biomarker for atherosclerosis in patients with systemic lupus erythematosus and rheumatoid arthritis. Arthr Rheum 2006;54(8):2541-9.</p><p>Ananth L., Prete P.E., Kashyap M.L. Apolipoproteins A-I and B and cholesterol in synovial fluid of patients with rheumatoid arthritis. Metabolism 1993;42(7):803-6.</p><p>Woods A., Brull D.J., Humphries S.E. et al. Genetics of inflammation and risk of coronary artery disease: the central role of interleukin-6. Eur Heart J 2000;21:1574-83.</p><p>Popa C., Netea M.G., Radstake T.R. et al. Markers of inflammation are negatively correlated with serum leptin in rheumatoid arthritis. Ann Rheum Dis 2005;64:303-5.</p><p>Nashimoto N., Yoshizaki K., Miyasaka 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.</p><p>Sattar N. Effect of tocilizumab treatment on lipid parameters (pooled data: OPTION &amp; TOWARD). Roche (data on file)</p><p>Maini R.N., Taylor P.C., 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.</p><p>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 randomized controlled trial of tocilizumab. Ann Rheum Dis 2007;66:1162-7.</p><p>Schimmel E.K., Yazici Y. Increased lipid levels but unchanged atherogenic index in rheumatoid artritis patients treated with biologic disease modifying antirheumatic drugs: published experience. Clin Exp Rheumatol 2009;27:446-51.</p></div><br />

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