Rheumatology
doi: 10.25005/2074-0581-2017-19-1-78-84
EVALUATION OF EFFECTIVENESS OF INFLUENCE OF THE SUBCUTANEOUS FORM OFMETHOTREXATUM TO THE LEVEL OF PRO-INFLAMMATORY CYTOKINEMIA AND THE MORPHOFUNCTIONAL STATE OF VASCULAR WALL IN PATIENTS WITH RHEUMATOID ARTHRITIS
1Department of Internal Diseases №1, Kursk State Medical University, Kursk, Russia
2Department of Propedeutics of Internal Diseases, Avicenna Tajik State Medical University, Dushanbe, Tajikistan
Objective: To assess the effect of the subcutaneous form of methotrexatum (metoject) on the level of pro-inflammatory cytokinemia and the morphofunctional characteristics of the vascular wall in patients with rheumatoid arthritis.
Methods: The level of pro-inflammatory cytokinemia and the morphofunctional characteristics of carotid arteries were studied in 94 patients with rheumatoid arthritis (RA) positive for RF-IgM and/or anti-citrullinated protein antibody (ACPA).
Results: It has been established that in patients with RA as a result of an increase in the serum concentration of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) the subclinical lesion of the major arteries, manifested by an increase in the thickness of the intima-media complex (IMC) and the stiffness index of the common carotid artery (CCA) was observed, the magnitude of which was correlated with the duration of RA, the activity index of DAS28, the level of RF and the concentration of ACPA. The use of metoject in RA patients led to a statistically significant decrease in the DAS28 index, a decrease in pro-inflammatory cytokinemia with attainment of control values in the early stages of the disease, a decrease in the thickness of IMC of the CCA, and local (carotid) rigidity of the vascular bed, which is more pronounced with RA duration less than 2 years. It was demonstrated that metoject therapy along with high anti-inflammatory activity, possesses a vasoprotective effect, which is characterized by a decrease in remodeling signs of CCA.
Conclusion: The results of the study confirm not only the high clinical efficiency and good tolerancy of the subcutaneous form of metoject, but also show that it possesses a high anti-inflammatory activity, which provides a vasoprotective effect on large vessels of the elastic type (aorta and common carotid arteries).
Keywords: Rheumatoid arthritis, methotrexatum, metoject, thickness of intima-media complex, common carotid artery, pro-inflammatory cytokines.
References
- Nasonov EL. Metotreksat pri revmatoidnom artrite: novye fakty i idei [Methotrexate in rheumatoid arthritis: New facts and ideas]. Nauchno-prakticheskaya revmatologiya [Scientific and practical rheumatology]. 2015; 53(4):421-33. Available from: http://dx.doi.org/10.14412/1995-4484-2015-421-433.
- Popkova TV, Novikova DS, Nasonov EL. Kardiovaskulyarnye faktory riska pri revmaticheskikh zabolevaniyakh: svyaz’ s vospaleniem [Cardiovascular risk factors for rheumatic diseases: association with inflammation]. Consilium Medicum [Consilium Medicum]. 2010;2:112-8.
- Antongiulio S, Fabio MP, Francesca C. Beyond the joint: Subclinical atherosclerosis in rheumatoid arthritis. World J Orthop. 2014;5(3):328-35. Available from: http://dx.doi.org/10.5312/wjo.v5.i3.328.
- Nasonov EL. Progress revmatologii v nachale XXI veka [Progress of rheumatology in the beginning of the XXI century]. Sovremennaya revmatologiya [Modern rheumatology]. 2014;3:4-8.
- Nasonov EL, Karateev DE, Chichasova NV. Novye rekomendatsii po lecheniyu revmatoidnogo artrita (EULAR, 2013): mesto metotreksata [New recommendations for the treatment of rheumatoid arthritis: the place of methotrexate] in: EULAR, 2013. Nauchno-prakticheskaya revmatologiya [Scientific and practical rheumatology]. 2014;52(1):8-26.
- Medved’ EE, Dubikov AI, Belogolovykh LA. Vliyanie metotreksata i leflunomida na tsitokinovyy profil’ i metabolizm oksida azota u bol’nykh revmatoidnym artritom [The effect of metatrekasate and leflunomide on the cytokine profile and the metabolism of nitric oxide in patients with rheumatoid arthritis]. Nauchno-prakticheskaya revmatologiya [Scientific and practical rheumatology].2006;4:58-62.
- Braun J, Kästner P, Flaxenberg P. Comparison of the clinical efficacy and safety of subcutaneous versus oral administration of methotrexate in patients with active rheumatoid arthritis: results of a six-month, multicenter, randomized, double-blind, controlled, phase IV trial. Arthritis Rheum. 2008;58(1):73-81. Available from: http://dx.doi.org/10.1002/art.23144.
- Karateev DE, Luchikhina EL, Murav’ev JuV. Pervoe rossiyskoe strategicheskoe issledovanie farmakoterapii revmatoidnogo artrita (REMARKA) [The first Russian strategic study of pharmacotherapy of rheumatoid arthritis (REMARKA)]. Nauchno-prakticheskaya revmatologiya [Scientific and practical rheumatology]. 2013;51(2):117-25. Available from: http://dx.doi. org/10.14412/1995-4484-2013-637.
- James HS, Claudia EK, Hurst RT. Use of carotid ultrasound to identify subclinical vascular disease and evaluate cardiovascular disease risk: a consensus statement from the American Society of Echocardiography Carotid Intima-Media Thickness Task Force. Endorsed by the Society for Vascular Medicine. J Am Soc Echocardiogr. 2008;21(2):93-111.
- Kawasaki T, Sasayama S, Yagi S. Noninvаsive meаsurement of the age related changes in stiffness if major branches of the human arteries. Cardiovasc Res. 1987;144:345-52. Available from: http://dx.doi.org/10.1016/j. echo.2007.11.011.
- Sella AP, Kristin A, Anne GS. Early prediction of increased arterial stiffness in patients with chronic inflammation: a 15-year follow-up study of 108 patients with rheumatoid arthritis. J Rheumatol. 2011;38(4):606-12. Available from: http://dx.doi.org/10.3899/jrheum.100689.
- Ristić GG, Lepić T, Glisić B. Rheumatoid arthritis is an independent risk factor for increased carotid intima-media thickness: impact of anti-inflammatory treatment. Rheumatology (Oxford). 2010;49(6):1076-81. Available from: http://dx.doi.org/10.1093/rheumatology/kep456.
- Van Sijl AM, Peters MJ, Knol DK. Carotid intima media thickness in rheumatoid arthritis as compared to control subjects: a meta-analysis. Semin Arthritis Rheum. 2011;40(5):389-97. Available from: http://dx.doi.org/10.1016/j. semarthrit.2010.06.006.
- Knyazeva LA, Meshcherina NS. Vliyanie terapii infliksimabom na uroven’ immunologicheskikh markyorov kardiovaskulyarnogo riska i remodelirovanie arterial’nogo rusla u bol’nykh revmatoidnym artritom [Influence of infliximab therapy on the level of immunological markers of cardiovascular risk and remodeling of the arterial bed in patients with rheumatoid arthritis]. Kurskiy nauchno-prakticheskiy vestnik «Chelovek i ego zdorov’e» [Kursk Scientific and Practical Bulletin «The Man and His Health»]. 2012;4:49-55.
- Dalbeni A, Giollo A, Tagetti A. Traditional cardiovascular risk factors or inflammation: Which factors accelerate atherosclerosis in arthritis patients? Int J Cardiol. 2017. pii: S0167-5273(16)33190-4. Available from: http:// dx.doi.org/10.1016/j.ijcard.2017.01.072. [Epub ahead of print].
- Alieva AS, Rotar’ OP, Konradi AO. Otsenka subklinicheskogo porazheniya sosudov na populyatsionnom urovne [Assessment of subclinical vascular disease at the population level]. Translyatsionnaya meditsina [Translational medicine]. 2014;2:26-38.
- Knyazeva LA, Meshcherina NS, Knyazeva LI, Goryaynov II, Stepchenko MA, Ponkratov VI. Vliyanie podkozhnoy formy metotreksata na strukturnofunktsional’noe sostoyanie sosudistoy stenki u bol’nykh revmatoidnym artritom [Effect of subcutaneous form of methotrexate on the structural and functional state of the vascular wall in patients with rheumatoid arthritis]. Nauchno-prakticheskaya revmatologiya [Scientific and practical rheumatology]. 2015;53(3):258-65. Available from: http://dx.doi. org/10.14412/1995-4484-2015-258-265.
- Mahmudov KR, Saidov YU, Zubaidov RN. Otsenka effektivnosti primeneniya metotreksata u bol’nykh s revmatoidnym artritom v svete implementatsii strategii «Treat-To-Target» v real’noy klinicheskoy praktike [Evaluation of the effectiveness of methotrexate in patients with rheumatoid arthritis in the light of the implementation of the «Treat-To-Target» strategy in real clinical practice]. Avicenna Bulletin (Vestnik Avitsenny). 2015;3:77-81.
Authors' information:
Knyazeva Larisa Aleksandrovna, Doctor of Medical Sciences, Full Professor, Professor at the Department of Internal Diseases № 1, Kursk State Medical University
Saidov Yor Umarovich, Doctor of Medical Sciences, Head of the Department of Propedeutics of Internal Diseases, Avicenna Tajik State Medical University
Knyazeva Larisa Ivanovna, Doctor of Medical Sciences, Full Professor, Head of the Department of Internal Diseases № 1, Kursk State Medical University
Mahmudov Hayom Ruziboevich, Assistant at the Department of Propedeutics of Internal Diseases, Avicenna Tajik State Medical University
Meshcherina Natalya Sergeevna, Doctor of Medical Sciences, Associate Professor at the Department of Internal Diseases № 1, Kursk State Medical University
Goryaynov Igor Ivanovich, Doctor of Medical Sciences, Full Professor, Professor at the Department of Internal Diseases № 1, Kursk State Medical University
Stepchenko Marina Aleksandrovna, Doctor of Medical Sciences, Full Professor, Professor at the Department of Internal Diseases № 1, Kursk State Medical University
Nikulina Irina Mihaylovna, Post-graduate student at the Department of Internal Diseases № 1, Kursk State Medical University
Kudinova Irina Sergeevna, Post-graduate student at the Department of Internal Diseases № 1, Kursk State Medical University
Conflicts of interest: No conflict
Address for correspondence:
Knyazeva Larisa Aleksandrovna
Doctor of Medical Sciences, Full Professor, Professor at the Department of Internal Diseases № 1, Kursk State Medical University
305007, Russia, Kursk, Sumskaya Street, 45-а
Tel.: (+7) 910 310 2827
E-mail: kafedra_n1@bk.ru
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