Multimedialna platforma wiedzy medycznej Internetowa Księgarnia Medyczna Kalendarium Konferencji
Rheumatology Forum
MENU
Shortcuts Submit an article Author Guidelines Ahead Of Print Editorial Team

open access

Vol 9, No 2 (2023)
Review paper
Published online: 2023-06-13
View PDF Download PDF file
Get Citation

Antirheumatic drugs and cardiovascular disease in rheumatoid arthritis

Zoltán Szekanecz1, Gabriella Szűcs1, György Kerekes2
DOI: 10.5603/RF.2023.0010
·
Rheumatology Forum 2023;9(2):49-62.
Affiliations
  1. Department od Rheumatology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
  2. Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

open access

Vol 9, No 2 (2023)
Review
Published online: 2023-06-13

Abstract

There is increased cardiovascular (CV) morbidity and mortality in rheumatoid arthritis (RA) and other rheumatic and musculoskeletal diseases (RMDs). Systemic inflammation is highly involved in atherogenesis. Non-steroidal anti-inflammatory drugs (NSAIDs), primarily COX-2 inhibitors might increase CV risk. Corticosteroids might act as a double-edged sword as they exert both beneficial and negative effectson the CV system. NSAIDs and corticosteroids are anti-inflammatory, but, on the other hand, they might be potentially atherogenic. Conventional synthetic DMARDs (csDMARDs), such as antimalarials, methotrexate, sulfasalazine, leflunomide and cyclosporine A have good CV safety, however, leflunomide and cyclosporine A might cause hypertension. Biologic DMARDs, by suppressing inflammation and disease activity, might either reduce CV risk or at least not cause any harm in that respect. Recently, tofacitinib and most likely other Janus kinase inhibitors have been associated with increased CV risk, at least in RMD patients with high CV risk at baseline. In clinical practice, EULAR and other recommendations guide the rheumatologist when screening for and managing CV comorbidities.

Abstract

There is increased cardiovascular (CV) morbidity and mortality in rheumatoid arthritis (RA) and other rheumatic and musculoskeletal diseases (RMDs). Systemic inflammation is highly involved in atherogenesis. Non-steroidal anti-inflammatory drugs (NSAIDs), primarily COX-2 inhibitors might increase CV risk. Corticosteroids might act as a double-edged sword as they exert both beneficial and negative effectson the CV system. NSAIDs and corticosteroids are anti-inflammatory, but, on the other hand, they might be potentially atherogenic. Conventional synthetic DMARDs (csDMARDs), such as antimalarials, methotrexate, sulfasalazine, leflunomide and cyclosporine A have good CV safety, however, leflunomide and cyclosporine A might cause hypertension. Biologic DMARDs, by suppressing inflammation and disease activity, might either reduce CV risk or at least not cause any harm in that respect. Recently, tofacitinib and most likely other Janus kinase inhibitors have been associated with increased CV risk, at least in RMD patients with high CV risk at baseline. In clinical practice, EULAR and other recommendations guide the rheumatologist when screening for and managing CV comorbidities.

Full Text:

View PDF Download PDF file
Get Citation

Keywords

rheumatoid arthritis; RMDs; atherosclerosis; cardiovascular disease; antirheumatic drugs; csDMARDs; bDMARDs; tsDMARDs

About this article
Title

Antirheumatic drugs and cardiovascular disease in rheumatoid arthritis

Journal

Rheumatology Forum

Issue

Vol 9, No 2 (2023)

Article type

Review paper

Pages

49-62

Published online

2023-06-13

Page views

1357

Article views/downloads

227

DOI

10.5603/RF.2023.0010

Bibliographic record

Rheumatology Forum 2023;9(2):49-62.

Keywords

rheumatoid arthritis
RMDs
atherosclerosis
cardiovascular disease
antirheumatic drugs
csDMARDs
bDMARDs
tsDMARDs

Authors

Zoltán Szekanecz
Gabriella Szűcs
György Kerekes

References (135)
  1. Szekanecz Z, Kerekes G, Der H, et al. Accelerated atherosclerosis in rheumatoid arthritis. Ann N Y Acad Sci. 2007; 1108: 349–358.
    CrossRefPubMed
  2. Shoenfeld Y, Gerli R, Doria A, et al. Accelerated atherosclerosis in autoimmune rheumatic diseases. Circulation. 2005; 112(21): 3337–3347.
    CrossRefPubMed
  3. Kaplan MJ. Management of cardiovascular disease risk in chronic inflammatory disorders. Nat Rev Rheumatol. 2009; 5(4): 208–217.
    CrossRefPubMed
  4. Agca R, Heslinga SC, Rollefstad S, et al. EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update. Ann Rheum Dis. 2017; 76(1): 17–28.
    CrossRefPubMed
  5. Drosos GC, Vedder D, Houben E, et al. EULAR recommendations for cardiovascular risk management in rheumatic and musculoskeletal diseases, including systemic lupus erythematosus and antiphospholipid syndrome. Ann Rheum Dis. 2022; 81(6): 768–779.
    CrossRefPubMed
  6. Błyszczuk P, Szekanecz Z. Pathogenesis of ischaemic and non-ischaemic heart diseases in rheumatoid arthritis. RMD Open. 2020; 6(1).
    CrossRefPubMed
  7. Peters MJL, van Halm VP, Voskuyl AE, et al. Does rheumatoid arthritis equal diabetes mellitus as an independent risk factor for cardiovascular disease? A prospective study. Arthritis Rheum. 2009; 61(11): 1571–1579.
    CrossRefPubMed
  8. Avina-Zubieta JA, Thomas J, Sadatsafavi M, et al. Risk of incident cardiovascular events in patients with rheumatoid arthritis: a meta-analysis of observational studies. Ann Rheum Dis. 2012; 71(9): 1524–1529.
    CrossRefPubMed
  9. Szekanecz Z, Kerekes G, Végh E, et al. Autoimmune atherosclerosis in 3D: How it develops, how to diagnose and what to do. Autoimmun Rev. 2016; 15(7): 756–769.
    CrossRefPubMed
  10. Szekanecz Z, Kerekes G, Kardos Z, et al. Mechanisms of inflammatory atherosclerosis in rheumatoid arthritis. Curr Immunol Rev. 2016; 12: 35–46.
  11. Gonzalez-Gay MA, Gonzalez-Juanatey C, Martin J. Rheumatoid arthritis: a disease associated with accelerated atherogenesis. Semin Arthritis Rheum. 2005; 35(1): 8–17.
    CrossRefPubMed
  12. Atzeni F, Rodríguez-Carrio J, Popa CD, et al. Cardiovascular effects of approved drugs for rheumatoid arthritis. Nat Rev Rheumatol. 2021; 17(5): 270–290.
    CrossRefPubMed
  13. Gonzalez A, Maradit Kremers H, Crowson CS, et al. The widening mortality gap between rheumatoid arthritis patients and the general population. Arthritis Rheum. 2007; 56(11): 3583–3587.
    CrossRefPubMed
  14. Atzeni F, Turiel M, Caporali R, et al. The effect of pharmacological therapy on the cardiovascular system of patients with systemic rheumatic diseases. Autoimmun Rev. 2010; 9(12): 835–839.
  15. Roubille C, Richer V, Starnino T, et al. The effects of tumour necrosis factor inhibitors, methotrexate, non-steroidal anti-inflammatory drugs and corticosteroids on cardiovascular events in rheumatoid arthritis, psoriasis and psoriatic arthritis: a systematic review and meta-analysis. Ann Rheum Dis. 2015; 74(3): 480–489.
    CrossRefPubMed
  16. Gasparyan AY, Ayvazyan L, Cocco G, et al. Adverse cardiovascular effects of antirheumatic drugs: implications for clinical practice and research. Curr Pharm Des. 2012; 18(11): 1543–1555.
    CrossRefPubMed
  17. Smolen JS, Landewé RBM, Bergstra SA, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Ann Rheum Dis. 2023; 82(1): 3–18.
    CrossRefPubMed
  18. Szekanecz Z, Kerekes G, Soltész P, et al. Vascular effects of biologic agents in RA and spondyloarthropathies. Nat Rev Rheumatol. 2009; 5(12): 677–684.
    CrossRefPubMed
  19. Myasoedova E, Crowson CS, Kremers HM, et al. Lipid paradox in rheumatoid arthritis: the impact of serum lipid measures and systemic inflammation on the risk of cardiovascular disease. Ann Rheum Dis. 2011; 70(3): 482–487.
    CrossRefPubMed
  20. Liu Yj, Wang Zg, Li Zl, et al. Effect of arthroscopic debridement for adolescent ankylosing spondylitis with early hip-joint disease [article in Chinese]. Zhonghua Yi Xue Za Zhi. 2010; 90(15): 1048–1050.
    PubMed
  21. Kearney PM, Baigent C, Godwin J, et al. Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials. BMJ. 2006; 332(7553): 1302–1308.
    CrossRefPubMed
  22. McGettigan P, Henry D. Cardiovascular risk and inhibition of cyclooxygenase: a systematic review of the observational studies of selective and nonselective inhibitors of cyclooxygenase 2. JAMA. 2006; 296(13): 1633–1644.
    CrossRefPubMed
  23. Nurmohamed MT, van Halm VP, Dijkmans BAC. Cardiovascular risk profile of antirheumatic agents in patients with osteoarthritis and rheumatoid arthritis. Drugs. 2002; 62(11): 1599–1609.
    CrossRefPubMed
  24. Scott PA, Kingsley GH, Smith CM, et al. Non-steroidal anti-inflammatory drugs and myocardial infarctions: comparative systematic review of evidence from observational studies and randomised controlled trials. Ann Rheum Dis. 2007; 66(10): 1296–1304.
    CrossRefPubMed
  25. Nissen SE, Yeomans ND, Solomon DH, et al. Cardiovascular safety of celecoxib, naproxen, or ibuprofen for arthritis. N Engl J Med. 2016; 375(26): 2519–2529.
    CrossRefPubMed
  26. Tsai WC, Ou TT, Yen JH, et al. Long-term frequent use of non-steroidal anti-inflammatory drugs might protect patients with ankylosing spondylitis from cardiovascular diseases: a nationwide case-control study. PLoS One. 2015; 10(5): e0126347.
    CrossRefPubMed
  27. Wanders A, Heijde Dv, Landewé R, et al. Nonsteroidal antiinflammatory drugs reduce radiographic progression in patients with ankylosing spondylitis: a randomized clinical trial. Arthritis Rheum. 2005; 52(6): 1756–1765.
    CrossRefPubMed
  28. Ardoin SP, Sundy JS. Update on nonsteriodal anti-inflammatory drugs. Curr Opin Rheumatol. 2006; 18(3): 221–226.
    CrossRefPubMed
  29. Sfikakis PP, Bournia VK, Kitas G, et al. Do non-steroidal anti-inflammatory drugs increase or decrease cardiovascular risk in patients with rheumatoid arthritis? Clin Exp Rheumatol. 2014; 32(6 Suppl 87): S8–S9.
    PubMed
  30. Lindhardsen J, Gislason GH, Jacobsen S, et al. Non-steroidal anti-inflammatory drugs and risk of cardiovascular disease in patients with rheumatoid arthritis: a nationwide cohort study. Ann Rheum Dis. 2014; 73(8): 1515–1521.
    CrossRefPubMed
  31. Goodson NJ, Brookhart AM, Symmons DP, et al. Non-steroidal anti-inflammatory drug use does not appear to be associated with increased cardiovascular mortality in patients with inflammatory polyarthritis: results from a primary care based inception cohort of patients. Ann Rheum Dis. 2009; 68(3): 367–372.
    CrossRefPubMed
  32. Peters MJL, Symmons DPM, McCarey D, et al. EULAR evidence-based recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other forms of inflammatory arthritis. Ann Rheum Dis. 2010; 69(2): 325–331.
    CrossRefPubMed
  33. Nurmohamed M. EULAR recommendation update on cardiovascular disease in RA. Ann Rheum Dis. 2015; 74(Suppl 2): 9.
  34. Bruce IN. Cardiovascular disease in lupus patients: should all patients be treated with statins and aspirin? Best Pract Res Clin Rheumatol. 2005; 19(5): 823–838.
    CrossRefPubMed
  35. Roos MA, Gennero L, Denysenko T, et al. Microparticles in physiological and in pathological conditions. Cell Biochem Funct. 2010; 28(7): 539–548.
    CrossRefPubMed
  36. Maxwell SR, Moots RJ, Kendall MJ. Corticosteroids: do they damage the cardiovascular system? Postgrad Med J. 1994; 70(830): 863–870.
    CrossRefPubMed
  37. Buttgereit F, Burmester GR, Lipworth BJ. Inflammation, glucocorticoids and risk of cardiovascular disease. Nat Clin Pract Rheumatol. 2009; 5(1): 18–19.
    CrossRefPubMed
  38. Konijn N, van Tu, Den Ui, et al. Prednisolone causes dose related unfavourable effects on body composition in early rheumatoid arthritis patients during the first year of treatment. Ann Rheum Dis. 2015; 74(Suppl 2): 239.
  39. Petri M, Lakatta C, Magder L, et al. Effect of prednisone and hydroxychloroquine on coronary artery disease risk factors in systemic lupus erythematosus: a longitudinal data analysis. Am J Med. 1994; 96(3): 254–259.
    CrossRefPubMed
  40. Karp I, Abrahamowicz M, Fortin PR, et al. Recent corticosteroid use and recent disease activity: independent determinants of coronary heart disease risk factors in systemic lupus erythematosus? Arthritis Rheum. 2008; 59(2): 169–175.
    CrossRefPubMed
  41. del Rincón I, Battafarano DF, Restrepo JF, et al. Glucocorticoid dose thresholds associated with all-cause and cardiovascular mortality in rheumatoid arthritis. Arthritis Rheumatol. 2014; 66(2): 264–272.
    CrossRefPubMed
  42. van Sijl AM, Boers M, Voskuyl AE, et al. Confounding by indication probably distorts the relationship between steroid use and cardiovascular disease in rheumatoid arthritis: results from a prospective cohort study. PLoS One. 2014; 9(1): e87965.
    CrossRefPubMed
  43. Boers M. Drugs and cardiovascular risk in inflammatory arthritis: another case of glucocorticoid-bashing? Ann Rheum Dis. 2015; 74(5): e33.
    CrossRefPubMed
  44. Boers M, Hartman L, Opris-Belinski D, et al. Low dose, add-on prednisolone in patients with rheumatoid arthritis aged 65+: the pragmatic randomised, double-blind placebo-controlled GLORIA trial. Ann Rheum Dis. 2022; 81(7): 925–936.
    CrossRefPubMed
  45. Ajeganova S, Svensson B, Hafström I, et al. Low-dose prednisolone treatment of early rheumatoid arthritis and late cardiovascular outcome and survival: 10-year follow-up of a 2-year randomised trial. BMJ Open. 2014; 4(4): e004259.
    CrossRefPubMed
  46. Toms TE, Panoulas VF, Douglas KMJ, et al. Lack of association between glucocorticoid use and presence of the metabolic syndrome in patients with rheumatoid arthritis: a cross-sectional study. Arthritis Res Ther. 2008; 10(6): R145.
    CrossRefPubMed
  47. Ruiz-Irastorza G, Ramos-Casals M, Brito-Zeron P, et al. Clinical efficacy and side effects of antimalarials in systemic lupus erythematosus: a systematic review. Ann Rheum Dis. 2010; 69(1): 20–28.
    CrossRefPubMed
  48. Rempenault C, Combe B, Barnetche T, et al. Metabolic and cardiovascular benefits of hydroxychloroquine in patients with rheumatoid arthritis: a systematic review and meta-analysis. Ann Rheum Dis. 2018; 77(1): 98–103.
    CrossRefPubMed
  49. Kerr G, Aujero M, Richards J, et al. Associations of hydroxychloroquine use with lipid profiles in rheumatoid arthritis: pharmacologic implications. Arthritis Care Res (Hoboken). 2014; 66(11): 1619–1626.
    CrossRefPubMed
  50. D'Andrea E, Desai RJ, He M, et al. Cardiovascular risks of hydroxychloroquine vs methotrexate in patients with rheumatoid arthritis. J Am Coll Cardiol. 2022; 80(1): 36–46.
    CrossRefPubMed
  51. van Halm VP, Nurmohamed MT, Twisk JWR, et al. Disease-modifying antirheumatic drugs are associated with a reduced risk for cardiovascular disease in patients with rheumatoid arthritis: a case control study. Arthritis Res Ther. 2006; 8(5): R151.
    CrossRefPubMed
  52. Furuichi K, Wada T, Sakai N, et al. Distinct expression of CCR1 and CCR5 in glomerular and interstitial lesions of human glomerular diseases. Am J Nephrol. 2000; 20(4): 291–299.
    CrossRefPubMed
  53. Peters MJL, Symmons DPM, McCarey D, et al. EULAR evidence-based recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other forms of inflammatory arthritis. Ann Rheum Dis. 2010; 69(2): 325–331.
    CrossRefPubMed
  54. Van Doornum S, McColl G, Wicks IP. Accelerated atherosclerosis: an extraarticular feature of rheumatoid arthritis? Arthritis Rheum. 2002; 46(4): 862–873.
    CrossRefPubMed
  55. Westlake SL, Colebatch AN, Baird J, et al. The effect of methotrexate on cardiovascular disease in patients with rheumatoid arthritis: a systematic literature review. Rheumatology (Oxford). 2010; 49(2): 295–307.
    CrossRefPubMed
  56. Micha R, Imamura F, Wyler von Ballmoos M, et al. Systematic review and meta-analysis of methotrexate use and risk of cardiovascular disease. Am J Cardiol. 2011; 108(9): 1362–1370.
    CrossRefPubMed
  57. Marks JL, Edwards CJ. Protective effect of methotrexate in patients with rheumatoid arthritis and cardiovascular comorbidity. Ther Adv Musculoskelet Dis. 2012; 4(3): 149–157.
    CrossRefPubMed
  58. Suissa S, Bernatsky S, Hudson M. Antirheumatic drug use and the risk of acute myocardial infarction. Arthritis Rheum. 2006; 55(4): 531–536.
    CrossRefPubMed
  59. Choi HK, Hernán MA, Seeger JD, et al. Methotrexate and mortality in patients with rheumatoid arthritis: a prospective study. Lancet. 2002; 359(9313): 1173–1177.
    CrossRefPubMed
  60. De Vecchis R, Baldi C, Palmisani L. Protective effects of methotrexate against ischemic cardiovascular disorders in patients treated for rheumatoid arthritis or psoriasis: novel therapeutic insights coming from a meta-analysis of the literature data. Anatol J Cardiol. 2016; 16(1): 2–9.
    CrossRefPubMed
  61. Ridker PM, Everett BM, Pradhan A, et al. CIRT Investigators. Low-Dose methotrexate for the prevention of atherosclerotic events. N Engl J Med. 2019; 380(8): 752–762.
    CrossRefPubMed
  62. Moreira DM, Lueneberg ME, da Silva RL, et al. MethotrexaTE THerapy in ST-Segment Elevation MYocardial InfarctionS: a randomized double-blind, placebo-controlled trial (TETHYS trial). J Cardiovasc Pharmacol Ther. 2017; 22(6): 538–545.
    CrossRefPubMed
  63. Feng H, Li XY, Zheng JR, et al. Inhibition of the nuclear factor-kappaB signaling pathway by leflunomide or triptolide also inhibits the anthralin-induced inflammatory response but does not affect keratinocyte growth inhibition. Biol Pharm Bull. 2005; 28(9): 1597–1602.
  64. Minoretti P, Bruno A, Di Vito C, et al. Leflunomide as an antiatherogenic drug. Med Hypotheses. 2007; 68(5): 1175–1176.
    CrossRefPubMed
  65. Grisar J, Aringer M, Köller MD, et al. Leflunomide inhibits transendothelial migration of peripheral blood mononuclear cells. Ann Rheum Dis. 2004; 63(12): 1632–1637.
    CrossRefPubMed
  66. Kellner H, Bornholdt K, Hein G. Leflunomide in the treatment of patients with early rheumatoid arthritis — results of a prospective non-interventional study. Clin Rheumatol. 2010; 29(8): 913–920.
    CrossRefPubMed
  67. Tanaka R, Takahashi Y, Kodama A, et al. Suppression of CCR5-tropic HIV type 1 infection by OX40 stimulation via enhanced production of β-chemokines. AIDS Res Hum Retroviruses. 2010; 26(10): 1147–1154.
    CrossRefPubMed
  68. Robert N, Wong GWk, Wright JM. Effect of cyclosporine on blood pressure. Cochrane Database Syst Rev. 2010(1): CD007893.
    CrossRefPubMed
  69. Roubille C, Martel-Pelletier J, Haraoui B, et al. Biologics and the cardiovascular system: a double-edged sword. Antiinflamm Antiallergy Agents Med Chem. 2013; 12(1): 68–82.
    CrossRefPubMed
  70. Ross R. Atherosclerosis — an inflammatory disease. N Engl J Med. 1999; 340(2): 115–126.
    CrossRefPubMed
  71. Grisar J, Aletaha D, Steiner CW, et al. Endothelial progenitor cells in active rheumatoid arthritis: effects of tumour necrosis factor and glucocorticoid therapy. Ann Rheum Dis. 2007; 66(10): 1284–1288.
    CrossRefPubMed
  72. Manfredi AA, Baldini M, Camera M, et al. Anti-TNFα agents curb platelet activation in patients with rheumatoid arthritis. Ann Rheum Dis. 2016; 75(8): 1511–1520.
    CrossRefPubMed
  73. Jacobsson LTH, Turesson C, Gülfe A, et al. Treatment with tumor necrosis factor blockers is associated with a lower incidence of first cardiovascular events in patients with rheumatoid arthritis. J Rheumatol. 2005; 32(7): 1213–1218.
    PubMed
  74. 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; 50(3): 518–531.
    CrossRefPubMed
  75. Dixon WG, Watson KD, Lunt M, et al. Reduction in the incidence of myocardial infarction in patients with rheumatoid arthritis who respond to anti-tumor necrosis factor alpha therapy: results from the British Society for Rheumatology Biologics Register. Arthritis Rheum. 2007; 56(9): 2905–2912.
    CrossRefPubMed
  76. Greenberg JD, Furer V, Farkouh ME. Cardiovascular safety of biologic therapies for the treatment of RA. Nat Rev Rheumatol. 2011; 8(1): 13–21.
    CrossRefPubMed
  77. Barnabe C, Martin BJ, Ghali WA. Systematic review and meta-analysis: anti-tumor necrosis factor α therapy and cardiovascular events in rheumatoid arthritis. Arthritis Care Res (Hoboken). 2011; 63(4): 522–529.
    CrossRefPubMed
  78. Ljung L, Askling J, Rantapää-Dahlqvist S, et al. The risk of acute coronary syndrome in rheumatoid arthritis in relation to tumour necrosis factor inhibitors and the risk in the general population: a national cohort study. Arthritis Res Ther. 2014; 16(3): R127.
    CrossRefPubMed
  79. Giles JT, Sattar N, Gabriel S, et al. Cardiovascular safety of tocilizumab versus etanercept in rheumatoid arthritis: a randomized controlled trial. Arthritis Rheumatol. 2020; 72(1): 31–40.
    CrossRefPubMed
  80. Ytterberg SR, Bhatt DL, Mikuls TR, et al. Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis. N Engl J Med. 2022; 386(4): 316–326.
    CrossRefPubMed
  81. Sarzi-Puttini P, Atzeni F, Shoenfeld Y, et al. TNF-alpha, rheumatoid arthritis, and heart failure: a rheumatological dilemma. Autoimmun Rev. 2005; 4(3): 153–161.
    CrossRefPubMed
  82. Ridker PM. High-sensitivity C-reactive protein, inflammation, and cardiovascular risk: from concept to clinical practice to clinical benefit. Am Heart J. 2004; 148(Suppl 1): S19–S26.
    CrossRefPubMed
  83. Kerekes G, Szekanecz Z, Der H, et al. Endothelial dysfunction and atherosclerosis in rheumatoid arthritis: a multiparametric analysis using imaging techniques and laboratory markers of inflammation and autoimmunity. J Rheumatol. 2008; 35(3): 398–406.
  84. Robertson J, Porter D, Sattar N, et al. Interleukin-6 blockade raises LDL via reduced catabolism rather than via increased synthesis: a cytokine-specific mechanism for cholesterol changes in rheumatoid arthritis. Ann Rheum Dis. 2017; 76(11): 1949–1952.
    CrossRefPubMed
  85. Protogerou AD, Zampeli E, Fragiadaki K, et al. A pilot study of endothelial dysfunction and aortic stiffness after interleukin-6 receptor inhibition in rheumatoid arthritis. Atherosclerosis. 2011; 219(2): 734–736.
    CrossRefPubMed
  86. Rao VU, Pavlov A, Klearman M, et al. An evaluation of risk factors for major adverse cardiovascular events during tocilizumab therapy. Arthritis Rheumatol. 2015; 67(2): 372–380.
    CrossRefPubMed
  87. Singh S, Fumery M, Singh AG, et al. Comparative risk of cardiovascular events with biologic and synthetic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis: a systematic review and meta-analysis. Arthritis Care Res (Hoboken). 2020; 72(4): 561–576.
    CrossRefPubMed
  88. Szekanecz Z, Koch AE, Kunkel SL, et al. Cytokines in rheumatoid arthritis. Potential targets for pharmacological intervention. Drugs Aging. 1998; 12(5): 377–390.
    CrossRefPubMed
  89. Ikonomidis I, Tzortzis S, Andreadou I, et al. Increased benefit of interleukin-1 inhibition on vascular function, myocardial deformation, and twisting in patients with coronary artery disease and coexisting rheumatoid arthritis. Circ Cardiovasc Imaging. 2014; 7(4): 619–628.
    CrossRefPubMed
  90. Ikonomidis I, Lekakis JP, Nikolaou M, et al. Inhibition of interleukin-1 by anakinra improves vascular and left ventricular function in patients with rheumatoid arthritis. Circulation. 2008; 117(20): 2662–2669.
    CrossRefPubMed
  91. Ridker PM, Howard CP, Walter V, et al. Effects of interleukin-1β inhibition with canakinumab on hemoglobin A1c, lipids, C-reactive protein, interleukin-6, and fibrinogen: a phase IIb randomized, placebo-controlled trial. Circulation. 2012; 126(23): 2739–2748.
    CrossRefPubMed
  92. Schlesinger N, Alten RE, Bardin T, et al. Canakinumab for acute gouty arthritis in patients with limited treatment options: results from two randomised, multicentre, active-controlled, double-blind trials and their initial extensions. Ann Rheum Dis. 2012; 71(11): 1839–1848.
    CrossRefPubMed
  93. Brogan PA, Hofer M, Kuemmerle-Deschner JB, et al. Use of canakinumab in the cryopyrin-associated periodic syndrome. N Engl J Med. 2009; 360(23): 2416–2425.
    CrossRefPubMed
  94. Howard C, Noe A, Skerjanec A, et al. Safety and tolerability of canakinumab, an IL-1β inhibitor, in type 2 diabetes mellitus patients: a pooled analysis of three randomised double-blind studies. Cardiovasc Diabetol. 2014; 13: 94.
    CrossRefPubMed
  95. Ridker PM, Everett BM, Thuren T, et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med. 2017; 377(12): 1119–1131.
    CrossRefPubMed
  96. Ridker PM, MacFadyen JG, Everett BM, et al. Relationship of C-reactive protein reduction to cardiovascular event reduction following treatment with canakinumab: a secondary analysis from the CANTOS randomised controlled trial. Lancet. 2018; 391(10118): 319–328.
    CrossRefPubMed
  97. Gravallese EM, Schett G. Effects of the IL-23-IL-17 pathway on bone in spondyloarthritis. Nat Rev Rheumatol. 2018; 14(11): 631–640.
    CrossRefPubMed
  98. Kerschbaumer A, Smolen JS, Dougados M, et al. Pharmacological treatment of psoriatic arthritis: a systematic literature research for the 2019 update of the EULAR recommendations for the management of psoriatic arthritis. Ann Rheum Dis. 2020; 79(6): 778–786.
    CrossRefPubMed
  99. Ramiro S, Nikiphorou E, Sepriano A, et al. ASAS-EULAR recommendations for the management of axial spondyloarthritis: 2022 update. Ann Rheum Dis. 2022; 82(1): 19–34.
    CrossRefPubMed
  100. Gossec L, Baraliakos X, Kerschbaumer A, et al. EULAR recommendations for the management of psoriatic arthritis with pharmacological therapies: 2019 update. Ann Rheum Dis. 2020; 79(6): 700–712.
    CrossRefPubMed
  101. Kerekes G, Soltész P, Dér H, et al. Effects of rituximab treatment on endothelial dysfunction, carotid atherosclerosis, and lipid profile in rheumatoid arthritis. Clin Rheumatol. 2009; 28(6): 705–710.
    CrossRefPubMed
  102. Gonzalez-Juanatey C, Llorca J, Vazquez-Rodriguez TR, et al. Short-term improvement of endothelial function in rituximab-treated rheumatoid arthritis patients refractory to tumor necrosis factor alpha blocker therapy. Arthritis Rheum. 2008; 59(12): 1821–1824.
    CrossRefPubMed
  103. Hsue PY, Scherzer R, Grunfeld C, et al. Depletion of B-cells with rituximab improves endothelial function and reduces inflammation among individuals with rheumatoid arthritis. J Am Heart Assoc. 2014; 3(5): e001267.
    CrossRefPubMed
  104. Kerekes G, Soltész P, Dér H, et al. Effects of rituximab treatment on endothelial dysfunction, carotid atherosclerosis, and lipid profile in rheumatoid arthritis. Clin Rheumatol. 2009; 28(6): 705–710.
    CrossRefPubMed
  105. Gürcan HM, Keskin DB, Stern JNH, et al. A review of the current use of rituximab in autoimmune diseases. Int Immunopharmacol. 2009; 9(1): 10–25.
    CrossRefPubMed
  106. Harrold LR, Reed GW, Magner R, et al. Comparative effectiveness and safety of rituximab versus subsequent anti-tumor necrosis factor therapy in patients with rheumatoid arthritis with prior exposure to anti-tumor necrosis factor therapies in the United States Corrona registry. Arthritis Res Ther. 2015; 17(1): 256.
    CrossRefPubMed
  107. Nurmohamed M, Choy E, Lula S, et al. The impact of biologics and tofacitinib on cardiovascular risk factors and outcomes in patients with rheumatic disease: a systematic literature review. Drug Saf. 2018; 41(5): 473–488.
    CrossRefPubMed
  108. Gottenberg JE, Morel J, Perrodeau E, et al. Comparative effectiveness of rituximab, abatacept, and tocilizumab in adults with rheumatoid arthritis and inadequate response to TNF inhibitors: prospective cohort study. BMJ. 2019; 364: l67.
    CrossRefPubMed
  109. Winthrop KL, Saag K, Cascino MD, et al. Long-term safety of rituximab in rheumatoid arthritis: analysis from the SUNSTONE registry. Arthritis Care Res (Hoboken. 2018; 71(8): 993–1003.
    CrossRefPubMed
  110. Sharif K, Watad A, Bragazzi NL, et al. Anterior ST-elevation myocardial infarction induced by rituximab infusion: A case report and review of the literature. J Clin Pharm Ther. 2017; 42(3): 356–362.
    CrossRefPubMed
  111. Sherer Y, Shoenfeld Y. Mechanisms of disease: atherosclerosis in autoimmune diseases. Nat Clin Pract Rheumatol. 2006; 2(2): 99–106.
    CrossRefPubMed
  112. Kobezda T, Ghassemi-Nejad S, Mikecz K, et al. Of mice and men: how animal models advance our understanding of T-cell function in RA. Nat Rev Rheumatol. 2014; 10(3): 160–170.
    CrossRefPubMed
  113. Maxwell L, Singh JA. Abatacept for rheumatoid arthritis. Cochrane Database Syst Rev. 2009; 2009(4): CD007277.
    CrossRefPubMed
  114. Zhang J, Xie F, Yun H, et al. Comparative effects of biologics on cardiovascular risk among older patients with rheumatoid arthritis. Ann Rheum Dis. 2016; 75(10): 1813–1818.
    CrossRefPubMed
  115. Jin Y, Kang EHa, Brill G, et al. Cardiovascular (CV) risk after initiation of abatacept versus TNF inhibitors in rheumatoid arthritis patients with and without baseline CV disease. J Rheumatol. 2018; 45(9): 1240–1248.
    CrossRefPubMed
  116. Kang EH, Jin Y, Brill G, et al. Comparative cardiovascular risk of abatacept and tumor necrosis factor inhibitors in patients with rheumatoid arthritis with and without diabetes mellitus: a multidatabase cohort study. J Am Heart Assoc. 2018; 7(3): e007393.
    CrossRefPubMed
  117. Vyas D, O'Dell KM, Bandy JL, et al. Tofacitinib: the first Janus kinase (JAK) inhibitor for the treatment of rheumatoid arthritis. Ann Pharmacother. 2013; 47(11): 1524–1531.
    CrossRefPubMed
  118. Yamaoka K, Tanaka Y. Targeting the Janus kinases in rheumatoid arthritis: focus on tofacitinib. Expert Opin Pharmacother. 2014; 15(1): 103–113.
    CrossRefPubMed
  119. Oh YB, Ahn M, Lee SM, et al. Inhibition of Janus activated kinase-3 protects against myocardial ischemia and reperfusion injury in mice. Exp Mol Med. 2013; 45(5): e23.
    CrossRefPubMed
  120. Soós B, Hamar A, Pusztai A, et al. Effects of tofacitinib therapy on arginine and methionine metabolites in association with vascular pathophysiology in rheumatoid arthritis: A metabolomic approach. Front Med (Lausanne). 2022; 9: 1011734.
    CrossRefPubMed
  121. Nash P, Kerschbaumer A, Dörner T, et al. Points to consider for the treatment of immune-mediated inflammatory diseases with Janus kinase inhibitors: a consensus statement. Ann Rheum Dis. 2021; 80(1): 71–87.
    CrossRefPubMed
  122. van Vollenhoven RF, Fleischmann R, Cohen S, et al. Tofacitinib or adalimumab versus placebo in rheumatoid arthritis. N Engl J Med. 2012; 367(6): 508–519.
    CrossRefPubMed
  123. Souto A, Salgado E, Maneiro JR, et al. Lipid profile changes in patients with chronic inflammatory arthritis treated with biologic agents and tofacitinib in randomized clinical trials: a systematic review and meta-analysis. Arthritis Rheumatol. 2015; 67(1): 117–127.
    CrossRefPubMed
  124. Winthrop KL. The emerging safety profile of JAK inhibitors in rheumatic disease. Nat Rev Rheumatol. 2017; 13(4): 234–243.
    CrossRefPubMed
  125. Mease P, Charles-Schoeman C, Cohen S, et al. Incidence of venous and arterial thromboembolic events reported in the tofacitinib rheumatoid arthritis, psoriasis and psoriatic arthritis development programmes and from real-world data. Ann Rheum Dis. 2020; 79(11): 1400–1413.
    CrossRefPubMed
  126. Szekanecz Z, Hamar A, Soós B. Safety issues of JAK inhibitors in rheumatoid arthritis (Hungarian). Immunol Quarterly (Budapest). 2021; 13(1): 5–20.
  127. Szekanecz Z. Pro-inflammatory cytokines in atherosclerosis. Isr Med Assoc J. 2008; 10(7): 529–530.
    PubMed
  128. Hamar A, Hascsi Z, Pusztai A, et al. Prospective, simultaneous assessment of joint and vascular inflammation by PET/CT in tofacitinib-treated patients with rheumatoid arthritis: associations with vascular and bone status. RMD Open. 2021; 7(3).
    CrossRefPubMed
  129. Charles-Schoeman C, Buch MH, Dougados M, et al. Risk of major adverse cardiovascular events with tofacitinib versus tumour necrosis factor inhibitors in patients with rheumatoid arthritis with or without a history of atherosclerotic cardiovascular disease: a post hoc analysis from ORAL Surveillance. Ann Rheum Dis. 2023; 82(1): 119–129.
    CrossRefPubMed
  130. Cohen SB, Tanaka Y, Mariette X, et al. Long-term safety of tofacitinib for the treatment of rheumatoid arthritis up to 8.5 years: integrated analysis of data from the global clinical trials. Ann Rheum Dis. 2017; 76(7): 1253–1262.
    CrossRefPubMed
  131. Cohen SB, van Vollenhoven RF, Winthrop KL, et al. Safety profile of upadacitinib in rheumatoid arthritis: integrated analysis from the SELECT phase III clinical programme. Ann Rheum Dis. 2021; 80(3): 304–311.
    CrossRefPubMed
  132. Genovese MC, Winthrop K, Tanaka Y, et al. THU0202 integrated safety analysis of filgotinib treatment for rheumatoid arthritis from 7 clinical trials. Ann Rheum Dis. 2020; 79(Suppl 1): 324–325.
    CrossRef
  133. Genovese M, Smolen JS, Takeuchi T, et al. Safety profile of baricitinib for the treatment of rheumatoid arthritis up to 8.4 years: an updated integrated safety analysis. Ann Rheum Dis. 2020; 79(Suppl 1): 638.
  134. Xie W, Huang Y, Xiao S, et al. Impact of Janus kinase inhibitors on risk of cardiovascular events in patients with rheumatoid arthritis: systematic review and meta-analysis of randomised controlled trials. Ann Rheum Dis. 2019; 78(8): 1048–1054.
    CrossRefPubMed
  135. EMA confirms measures to minimise risk of serious side effects with Janus kinase inhibitors for chronic inflammatory disorders. https://wwwemaeuropaeu/en/news/ema-confirms-measures-minimise-risk-serious-side-effects-janus-kinase-inhibitors-chronic (2022).

Regulations

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

By VM Media Group sp. z o.o., Świętokrzyska 73, 80–180 Gdańsk, Poland
tel.:+48 58 320 94 94, fax:+48 58 320 94 60, e-mail: viamedica@viamedica.pl