THE EFFECT OF GOLIMUMAB ON ARTERIAL STIFFNESS IN PATIENTS WITH RHEUMATOID ARTHRITIS

Objective: to evaluate the effect of golimumab (GLM) on arterial stiffness in patients with different clinical and immunological subtypes of rheumatoid arthritis (RA).

Material and methods. Examinations were made in 48 patients with RA meeting the 1987 ACR/2010 EULAR classification criteria. The investigators visualized carotid arteries with determination of local vessel wall stiffness and studied regional arterial stiffness with assessment of contour pulse wave analysis before and 52 weeks after initiation of therapy.

Results and discussion. Young and middle-aged RA patients without any concomitant cardiovascular diseases were found to have subclinical great artery involvement that was characterized by increases in intima-media thickness (IMT) and stiffness index β of the common carotid artery (CCA); by rises in peripheral augmentation index (AIp), stiffness index (SI), and reflection index (RI), the intensity of a change in which was associated with high DAS28 and seropositivity for rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide (antiCCP) antibodies. GLM treatment in patients with RA was accompanied by a statistically significant decrease in DAS28 and a reduction in CCA IMT and local (carotid) stiffness of the vascular bed. More significant correction of the investigated parameters was achieved in patients with the seronegative subtype of the disease; in this group of patients, CCA IMT decreased by 29% by the end of observation (p=0.01), CCA SI β reduced by an average of 28.7% (p=0.0001). At 52 weeks after GLM therapy initiation, contour pulse wave analysis indicated that this subgroup of patients was observed to have decreases in AIp, SI, and RI to the control level; in RA seropositive for RF and/or anti-CCP, they reduced by an average of 1.8 (p=0.0001), 1.2 (p=0.005) and 1.6 (p=0.001) times, respectively.

Conclusion. Along with high anti-inflammatory activity, GLM therapy in patients with RA has a vasoprotective effect on the walls of large elastic-type vessels (decreases in CCA IMT and SI β, AIp, and SI) and small muscular-type arteries (a reduction in RI). 

1. Alemao E, Cawston H, Bourhis F, et al. Cardiovascular risk factor management in patients with RA compared to matched non-RA patients. Rheumatology (Oxford). 2016 May;55(5):809-16. doi: 10.1093/rheumatology/kev427

2. Meune C, Touze E, Trinquart L, Allanore Y. High risk of clinical cardiovascular events in RA: levels of associations of myocardial infarction and stroke through a systematic review and meta-analysis. Arch Cardiovasc Dis. 2010;103:253-61. doi: 10.1016/j.acvd.2010.03.007

3. Горбунова ЮН, Новикова ДС, Попкова ТВ и др. Кардиоваскулярный риск у больных ранним ревматоидным артритом до назначения базисной противовоспалительной терапии (предварительные данные исследования РЕМАРКА). Научно-практическая ревматология. 2014;52(4):381-6 [Gorbunova YuN, Novikova DS, Popkova TV, et al. Cardiovascular risk in patients with early rheumatoid arthritis before disease-modifying antirheumatic therapy (preliminary data of the REMARCА study). Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2014;52(4):381-6 (In Russ.)]. doi: 10.14412/1995-4484-2014-381-386

4. Удачкина ЕВ, Новикова ДС, Попкова ТВ и др. Динамика липидных параметров крови у больных ранним ревматоидным артритом на фоне противоревматической терапии, проводимой по принципу «Лечение до достижения цели» (по данным 18-месячного наблюдения). Научнопрактическая ревматология. 2016;54(2):164-70 [Udachkina EV, Novikova DS, Popkova TV, et al. Time course of changes in blood lipid parameters in patients with early rheumatoid arthritis during treat-to-target antirheumatic therapy: According to 18-month follow-up findings. Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2016;54(2):164-70 (In Russ.)]. doi: 10.14412/1995-4484-2016-164-170

5. Попкова ТВ, Новикова ДС, Насонов ЕЛ. Сердечно-сосудистые заболевания при ревматоидном артрите: новые данные. Научно-практическая ревматология. 2016;54(2):122-8 [Popkova TV, Novikova DS, Nasonov EL. Cardiovascular diseases in rheumatoid arthritis: Latest data. Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2016;54(2):1228 (In Russ.)]. doi: 10.14412/1995-4484-2016-122-128

6. Van Bortel LM, Laurent S, Boutouyrie P, et al. Expert consensus document on the measurement of aortic stiffness in daily practice using carotid-femoral pulse wave velocity. J Hypertens. 2012 Mar;30(3):445-8. doi: 10.1097/HJH.0b013e32834fa8b0

7. Laurent S, Cockcroft J, van Bortel LM, et al. Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J. 2006;27:2588-605. doi: 10.1093/eurheartj/ehl2542006

8. Vazquez-Del MM, Gomez-Banuelos E, Chavarria-Avila E, et al. Disease duration of rheumatoid arthritis is a predictor of vascular stiffness: a cross-sectional study in patients without known cardiovascular comorbidities: A STROBE-compliant article. Medicine (Baltimore). 2017 Aug;96(33):e7862. doi: 10.1097/MD.0000000000007862

9. Ambrosino P, Lupoli R, Di Minno A, et al. Subclinical atherosclerosis in patients with rheumatoid arthritis. A meta-analysis of literature studies. Thromb Haemost. 2015 May;113(5):916-30. doi: 10.1160/TH14-11-0921. Epub 2015 Feb 26.

10. Arida A, Zampeli E, Konstantonis G, et al. Rheumatoid arthritis is sufficient to cause atheromatosis but not arterial stiffness or hypertrophy in the absence of classical cardiovascular risk factors. Clin Rheumatol. 2015 May;34(5):853-9. doi: 10.1007/s10067-0152914-1. Epub 2015 Mar 11.

11. Libby P. Role of inflammation in atherosclerosis associated with rheumatoid arthritis. Am J Med. 2008 Oct;121(10 Suppl 1):S21-31. doi: 10.1016/j.amjmed.2008.06.014

12. Arida A, Protogerou AD, Konstantonis G, et al. Atherosclerosis is not accelerated in rheumatoid arthritis of low activity or remission, regardless of antirheumatic treatment modalities. Rheumatology (Oxford). 2017 Jun 1;56(6):934-9. doi: 10.1093/rheumatology/kew506

13. Smolen JS, Landewe 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. 2014 Mar;73(3):492-509. doi: 10.1136/annrheumdis-2013-204573

14. Насонов ЕЛ. Фармакотерапия ревматоидного артрита: российские и международные рекомендации. Научнопрактическая ревматология. 2016;54(5):557-71 [Nasonov EL. Pharmacotherapy for rheumatoid arthritis: Russian and International guidelines. A pilot study. Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2016;54(5):557-71 (In Russ.)]. doi: 10.14412/1995-4484-2016557-571

15. Насонов ЕЛ, Мазуров ВИ, Каратеев ДЕ и др. Проект рекомендаций по лечению ревматоидного артрита Общероссийской общественной организации «Ассоциация ревматологов России» – 2014 (часть 1). Научно-практическая ревматология. 2014;52(5):477-94 [Nasonov EL, Mazurov VI, Karateev DE, et al. Spondyloarthritis: Evolution of a concept. Project: recommendations on treatment of rheumatoid arthritis developed by All-Russian Public organization «Association of Rheumatologists of Russia» – 2014 (part 1). NauchnoPrakticheskaya Revmatologiya = Rheumatology Science and Practice. 2014;52(5):477-94 (In Russ.)]. doi: 10.14412/1995-44842014-477-494

16. Westlake SL, Colebatch AN, Baird J, et al. Tumour necrosis factor antagonists and the risk of cardiovascular disease in patients with rheumatoid arthritis: a systematic literature review. Rheumatology (Oxford). 2011,Mar;50(3):518-31. doi: 10.1093/rheumatology/keq316

17. Mäki-Petäjä KM, Wilkinson IB. Anti-inflammatory drugs and statins for arterial stiffness reduction. Curr Pharm Des. 2009;15(3):290-303. doi: 10.2174/138161209787354221

18. Князева ЛА, Мещерина НС. Влияние инфликсимаба на параметры ремоделирования артериального русла, уровень RANKL и остеопротегерина у больных ревматоидным артритом. Научно-практическая ревматология. 2013;51(6):666-70 [Knyazeva LA, Meshcherina NS. Effect of infliximab on parameters of remodeling of arterial bloodstream, RANKL and osteoprotegerin levels in patients with rheumatoid arthritis. Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2013;51(6):666-70 (In Russ.)]. doi: 10.14412/1995-4484-2013-666-70

19. Navarro-Millan I, Charles-Schoeman C, Yang S, et al. Changes in lipoproteins associated with treatment with methotrexate or combination therapy in early rheumatoid arthritis: results from the TEAR trial. Arthritis Rheum. 2013;65(6):1430-8. doi: 10.1002/art.37916 12

20. Popa C, van den Hoogen FH, Radstake TR, et al. Modulation of lipoprotein plasma concentrations during long-term anti-TNF therapy in patients with active rheumatoid arthritis. Ann Rheum Dis. 2007 Nov;66(11):1503-7. doi: 10.1136/ard.2006.066191

21. Насонов ЕЛ, редактор. Генно-инженерные биологические препараты в лечении ревматоидного артрита. Москва: ИМАПРЕСС; 2013. 549 с. [Nasonov EL, editor. Genno-inzhenernye biologicheskie preparaty v lechenii revmatoidnogo artrita [Genetically engineered biological agents in the treatment of rheumatoid arthritis]. Moscow: IMA-PRESS; 2013. 549 p.].

22. Sandoo A, Hodson J, Douglas KM, et al. The association between functional and morphological assessments of endothelial function in patients with rheumatoid arthritis: a cross-sectional study. Arthritis Res Ther. 2013;15(5):R107. doi: 10.1186/ar4287

23. Kiortsis DN, Mavridis AK. Effects of infliximab lipoprotein profile in patients with rheumatoid arthritis and ankylosing spondylitis. J Rheum Dis. 2006;33:4921-3.

24. Yun H, Xie F, Delzell E, et al. The comparative effectiveness of biologics among older adults and disabled rheumatoid arthritis patients in the Medicare population. Br J Clin Pharmacol. 2015 Dec;80(6):1447-57. doi: 10.1111/bcp.12709

25. Inzinger M, Wippel-Slupetzky K, Weger W, et al. Survival and Effectiveness of Tumour Necrosis Factor-alpha Inhibitors in the Treatment of Plaque Psoriasis under Daily Life Conditions: Report from the Psoriasis Registry Austria. Acta Derm Venereol. 2016 Feb;96(2):207-12. doi: 10.2340/00015555-2214

26. Shealy DJ, Cai A, Staquet K, et al. Characterization of golimumab, a human monoclonal antibody specific for human tumor necrosis factor α. MAbs. 2010 Jul-Aug;2(4):428-39. doi: 10.4161/mabs.12304

27. Voulgari PV. Emerging drugs for rheumatoid arthritis. Expert Opin Emerg Drugs. 2008 Mar;13(1):175-96. doi: 10.1517/14728214.13.1.175

28. Чичасова НВ. Ингибитор фактора некроза опухоли α голимумаб в лечении ревматоидного артрита. Современная ревматология. 2014;(4):76-85 [Chichasova NV. The tumor necrosis factor-α inhibitor golimumab in the treatment of rheumatoid arthritis. Sovremennaya Revmatologiya = Modern Rheumatology Journal. 2014;8(4):76-85 (In Russ.)]. doi: 10.14412/1996-7012-2014-4-76-85

29. Кардиоваскулярная профилактика: национальные рекомендации. Кардиоваскулярная терапия и профилактика. 2011;10 (Прил. 2):64 [Cardiovascular prevention: national guidelines. Kardiovaskulyarnaya Terapiya i Profilaktika = Cardiovascular Therapy and Prevention. 2011;10 Suppl 2:64 (In Russ.)].

30. 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.

31. Парфенов АС. Экспресс-диагностика сердечно-сосудистых заболевавний. Мир измерений. 2008;(6):74-82. [Parfenov AS. Express diagnostics of cardiovascular zabolevaniy. Mir Izmerenii = World Measurements. 2008;(6):74-82 (In Russ.)].

32. Мельникова ЛВ. Значение гемодинамических факторов в развитии ремоделирования сосудов мышечноэластического типа при артериальной гипертензии. Саратовский научно-медицинский журнал. 2011;7(1):76-9 [Melnikova LV. Importance of hemodynamic factors in vascular remodeling of muscular elastic type in arterial hypertension. Saratovskii Nauchno-Meditsinskii Zhurnal = Saratov Journal of Medical Scientific Research. 2011;7(1):76-9. (In Russ.)].

33. Dalbeni A, Giollo A, Tagetti A, et al. Traditional cardiovascular risk factors or inflammation: Which factors accelerate atherosclerosis in arthritis patients? Int J Cardiol. 2017, Jan 14. pii: S0167-5273(16)33190-4. doi: 10.1016/j.ijcard.2017.01.072. [Epub ahead of print].

34. Новикова ДС, Попкова ТВ, Кириллова ИГ и др. Оценка кардиоваскулярного риска у больных ранним ревматоидным артритом в рамках исследования РЕМАРКА (предварительные данные). Научно-практическая ревматология. 2015;53(1):24-31 [Novikova DS, Popkova TV, Kirillova IG, et al. Cardiovascular risk assessment in patients with early rheumatoid arthritis within the REMARCA study: Preliminary data. Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2015;53(1):24-31 (In Russ.)]. doi: 10.14412/1995-4484-2015-24-31

35. Van Sijl AM, Peters MJ, Knol DK, et al. Carotid intima media thickness in rheumatoid arthritis as compared to control subjects: a meta-analysis. Semin Arthritis Rheum. 2011;40:389-97. doi: 10.1016/ j.semarthrit.2010.06.006

36. Kirkham BW, Wasko MC, Hsia EC, et al. Effects of golimumab, an anti-tumour necrosis factor-α human monoclonal antibody, on lipids and markers of inflammation. Ann Rheum Dis. 2014 Jan;73(1):161-9. doi: 10.1136/annrheumdis-2012-202089

37. Bathon J, Wasko MC, Kirkham B, et al. Golimumab and cardiovascular disease: carotid artery ultrasound evaluation and cardiovascular adverse events. Ann Rheum Dis. 2010;69 (Suppl 3):464.

38. Wasko MC, Hsia EC, Kirkham B, et al. Effect of Golimumab on Carotid Atherosclerotic Disease Measures and Cardiovascular Events in Inflammatory Arthritides. J Clin Rheumatol. 2014 Jan;20(1):1-10. doi: 10.1097/RHU.0000000000000053