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Current Rheumatology Reports

, 16:459 | Cite as

Cardiovascular Risk and the Use of Biologic Agents in Rheumatoid Arthritis

  • Debbie T. Lim
  • Amy C. Cannella
  • Kaleb D Michaud
  • Ted R. MikulsEmail author
Health Economics and Quality of Life (M Harrison, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Health Economics and Quality of Life

Abstract

Although patients with rheumatoid arthritis (RA) are recognized to be disproportionately impacted by cardiovascular disease (CVD), effective approaches of primary and secondary CVD prevention have not been well defined in this population. Given their robust disease-modifying potential and effects on both pro-inflammatory and pro-atherogenic pathways, there has been substantial speculation that biologic treatments may serve as a means of providing highly effective RA disease control while simultaneously reducing CVD risk in this high risk group. In this review, we examine available evidence relevant to the associations of approved biologic treatments with CVD outcomes in the context of RA.

Keywords

Cardiovascular disease Myocardial infarction Rheumatoid arthritis Tumor necrosis factor Biologic Atherosclerosis 

Notes

Disclaimer

The view(s) expressed herein are those of the author(s) and do not reflect theofficial policy or position of the Veterans’ Affairs Medical Center.

Compliance with Ethics Guidelines

Conflict of Interest

None

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Avina-Zubieta JA, Choi HK, Sadatsafavi M, et al. Risk of cardiovascular mortality in patients with rheumatoid arthritis: A meta-analysis of observational studies. Arthritis Rheum. 2008;59(12):1690–7.PubMedCrossRefGoogle Scholar
  2. 2.
    Levy L, Fautrel B, Barnetche T, et al. Incidence and risk of fatal myocardial infarction and stroke events in rheumatoid arthritis patients. A systematic review of the literature. Clin Exp Rheumatol. 2008;26(4):673–9.PubMedGoogle Scholar
  3. 3.
    Nicola PJ, Maradit-Kremers H, Roger VL, et al. The risk of congestive heart failure in rheumatoid arthritis: A population-based study over 46 years. Arthritis Rheum. 2005;52(2):412–20.PubMedCrossRefGoogle Scholar
  4. 4.
    Solomon DH, Goodson NJ, Katz JN, et al. Patterns of cardiovascular risk in rheumatoid arthritis. Ann Rheum Dis. 2006;65(12):1608–12.PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    del Rincon ID, Williams K, Stern MP, et al. High incidence of cardiovascular events in a rheumatoid arthritis cohort not explained by traditional cardiac risk factors. Arthritis Rheum. 2001;44(12):2737–45.PubMedCrossRefGoogle Scholar
  6. 6.
    Kitas GD, Gabriel SE. Cardiovascular disease in rheumatoid arthritis: State of the art and future perspectives. Ann Rheum Dis. 2011;70(1):8–14.PubMedCrossRefGoogle Scholar
  7. 7.
    Maradit-Kremers H, Crowson CS, Nicola PJ, et al. Increased unrecognized coronary heart disease and sudden deaths in rheumatoid arthritis: A population-based cohort study. Arthritis Rheum. 2005;52(2):402–11.PubMedCrossRefGoogle Scholar
  8. 8.
    Banerjee S, Compton AP, Hooker RS, et al. Cardiovascular outcomes in male veterans with rheumatoid arthritis. Am J Cardiol. 2008;101(8):1201–5.PubMedCrossRefGoogle Scholar
  9. 9.
    Symmons DP, Gabriel SE. Epidemiology of CVD in rheumatic disease, with a focus on RA and SLE. Nat Rev Rheumatol. 2011;7(7):399–408.PubMedCrossRefGoogle Scholar
  10. 10.
    Goodson NJ, Symmons DP, Scott DG, et al. Baseline levels of C-reactive protein and prediction of death from cardiovascular disease in patients with inflammatory polyarthritis: A ten-year followup study of a primary care-based inception cohort. Arthritis Rheum. 2005;52(8):2293–9.PubMedCrossRefGoogle Scholar
  11. 11.
    Maradit-Kremers H, Nicola PJ, Crowson CS, et al. Cardiovascular death in rheumatoid arthritis: A population-based study. Arthritis Rheum. 2005;52(3):722–32.PubMedCrossRefGoogle Scholar
  12. 12.
    Tomasson G, Aspelund T, Jonsson T, et al. Effect of rheumatoid factor on mortality and coronary heart disease. Ann Rheum Dis. 2010;69(9):1649–54.PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Lopez-Longo FJ, Oliver-Minarro D, de la Torre I, et al. Association between anti-cyclic citrullinated peptide antibodies and ischemic heart disease in patients with rheumatoid arthritis. Arthritis Rheum. 2009;61(4):419–24.PubMedCrossRefGoogle Scholar
  14. 14.
    Arnab B, Biswadip G, Arindam P, et al. Anti-CCP antibody in patients with established rheumatoid arthritis: Does it predict adverse cardiovascular profile? J Cardiovasc Dis Res. 2013;4(2):102–6.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Arts EE, Fransen J, den Broeder AA, et al. The effect of disease duration and disease activity on the risk of cardiovascular disease in rheumatoid arthritis patients. Ann Rheum Dis. 2014. doi: 10.1136/2013/204531.Google Scholar
  16. 16.
    Everett BM, Pradhan AD, Solomon DH, et al. Rationale and design of the cardiovascular inflammation reduction trial: A test of the inflammatory hypothesis of atherothrombosis. Am Heart J. 2013;166(2):199–207.e15.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Morris SJ, Wasko MC, Antohe JL, et al. Hydroxychloroquine use associated with improvement in lipid profiles in rheumatoid arthritis patients. Arthritis Care Res (Hoboken). 2011;63(4):530–4.CrossRefGoogle Scholar
  18. 18.
    Mercer E, Rekedal L, Garg R, et al. Hydroxychloroquine improves insulin sensitivity in obese non-diabetic individuals. Arthritis Res Ther. 2012;14(3):R135.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Rozman B, Praprotnik S, Logar D, et al. Leflunomide and hypertension. Ann Rheum Dis. 2002;61(6):567–9.PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    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):1633–44.PubMedCrossRefGoogle Scholar
  21. 21.••
    Greenberg JD, Kremer JM, Curtis JR, et al. Tumour necrosis factor antagonist use and associated risk reduction of cardiovascular events among patients with rheumatoid arthritis. Ann Rheum Dis. 2011;70(4):576–82. An observational cohort study examining composite CV outcomes associated with the use of TNF antagonists in RA, with the provision of relative risks adjusted for other treatment exposures.PubMedCrossRefGoogle Scholar
  22. 22.
    Dessein PH, Joffe BI, Stanwix AE, et al. Glucocorticoids and insulin sensitivity in rheumatoid arthritis. J Rheumatol. 2004;31(5):867–74.PubMedGoogle Scholar
  23. 23.
    Girod JP, Brotman DJ. Does altered glucocorticoid homeostasis increase cardiovascular risk? Cardiovasc Res. 2004;64(2):217–26.PubMedCrossRefGoogle Scholar
  24. 24.
    Libby P. Role of inflammation in atherosclerosis associated with rheumatoid arthritis. Am J Med. 2008;121(10 Suppl 1):S21–31.PubMedCrossRefGoogle Scholar
  25. 25.
    Dixon WG, Symmons DP. What effects might anti-TNFalpha treatment be expected to have on cardiovascular morbidity and mortality in rheumatoid arthritis? A review of the role of TNFalpha in cardiovascular pathophysiology. Ann Rheum Dis. 2007;66(9):1132–6.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    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.PubMedGoogle Scholar
  27. 27.
    Wallberg-Jonsson S, Caidahl K, Klintland N, et al. Increased arterial stiffness and indication of endothelial dysfunction in long-standing rheumatoid arthritis. Scand J Rheumatol. 2008;37(1):1–5.PubMedCrossRefGoogle Scholar
  28. 28.
    Maki-Petaja KM, Hall FC, Booth AD, et al. Rheumatoid arthritis is associated with increased aortic pulse-wave velocity, which is reduced by anti-tumor necrosis factor-alpha therapy. Circulation. 2006;114(11):1185–92.PubMedCrossRefGoogle Scholar
  29. 29.
    Hurlimann D, Forster A, Noll G, et al. Anti-tumor necrosis factor-alpha treatment improves endothelial function in patients with rheumatoid arthritis. Circulation. 2002;106(17):2184–7.PubMedCrossRefGoogle Scholar
  30. 30.
    Bilsborough W, Keen H, Taylor A, et al. Anti-tumour necrosis factor-alpha therapy over conventional therapy improves endothelial function in adults with rheumatoid arthritis. Rheumatol Int. 2006;26(12):1125–31.PubMedCrossRefGoogle Scholar
  31. 31.
    Bosello S, Santoliquido A, Zoli A, et al. TNF-alpha blockade induces a reversible but transient effect on endothelial dysfunction in patients with long-standing severe rheumatoid arthritis. Clin Rheumatol. 2008;27(7):833–9.PubMedCrossRefGoogle Scholar
  32. 32.
    Gonzalez-Juanatey C, Llorca J, Sanchez-Andrade A, et al. Short-term adalimumab therapy improves endothelial function in patients with rheumatoid arthritis refractory to infliximab. Clin Exp Rheumatol. 2006;24(3):309–12.PubMedGoogle Scholar
  33. 33.
    Sidiropoulos PI, Siakka P, Pagonidis K, et al. Sustained improvement of vascular endothelial function during anti-TNFalpha treatment in rheumatoid arthritis patients. Scand J Rheumatol. 2009;38(1):6–10.PubMedCrossRefGoogle Scholar
  34. 34.
    Gonzalez-Juanatey C, Llorca J, Garcia-Porrua C, et al. Effect of anti-tumor necrosis factor alpha therapy on the progression of subclinical atherosclerosis in severe rheumatoid arthritis. Arthritis Rheum. 2006;55(1):150–3.PubMedCrossRefGoogle Scholar
  35. 35.
    Del Porto F, Lagana B, Lai S, et al. Response to anti-tumour necrosis factor alpha blockade is associated with reduction of carotid intima-media thickness in patients with active rheumatoid arthritis. Rheumatology (Oxford). 2007;46(7):1111–5.CrossRefGoogle Scholar
  36. 36.
    Wong M, Oakley SP, Young L, et al. Infliximab improves vascular stiffness in patients with rheumatoid arthritis. Ann Rheum Dis. 2009;68(8):1277–84.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Van Doornum S, McColl G, Wicks IP. Tumour necrosis factor antagonists improve disease activity but not arterial stiffness in rheumatoid arthritis. Rheumatology (Oxford). 2005;44(11):1428–32.CrossRefGoogle Scholar
  38. 38.
    Daien CI, Duny Y, Barnetche T, et al. Effect of TNF inhibitors on lipid profile in rheumatoid arthritis: A systematic review with meta-analysis. Ann Rheum Dis. 2012;71(6):862–8.PubMedCrossRefGoogle Scholar
  39. 39.
    Tam LS, Tomlinson B, Chu TT, et al. Impact of TNF inhibition on insulin resistance and lipids levels in patients with rheumatoid arthritis. Clin Rheumatol. 2007;26(9):1495–8.PubMedCrossRefGoogle Scholar
  40. 40.
    Gonzalez-Gay MA, De Matias JM, Gonzalez-Juanatey C, et al. Anti-tumor necrosis factor-alpha blockade improves insulin resistance in patients with rheumatoid arthritis. Clin Exp Rheumatol. 2006;24(1):83–6.PubMedGoogle Scholar
  41. 41.
    Kiortsis DN, Mavridis AK, Vasakos S, et al. Effects of infliximab treatment on insulin resistance in patients with rheumatoid arthritis and ankylosing spondylitis. Ann Rheum Dis. 2005;64(5):765–6.PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Stagakis I, Bertsias G, Karvounaris S, et al. Anti-tumor necrosis factor therapy improves insulin resistance, beta cell function and insulin signaling in active rheumatoid arthritis patients with high insulin resistance. Arthritis Res Ther. 2012;14(3):R141.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.••
    Barnabe C, Martin BJ, Ghali WA. Systematic review and meta-analysis: Anti-tumor necrosis factor alpha therapy and cardiovascular events in rheumatoid arthritis. Arthritis Care Res (Hoboken). 2011;63(4):522–9. A report of pooled relative risks associated with TNF inhibition in RA for the occurrence of CV outcomes. Although results suggest possible CV protection with anti-TNF in cohort studies, results must be interpreted with caution given evidence of study heterogeneity and possible publication bias.CrossRefGoogle Scholar
  44. 44.
    van de Putte LB, Atkins C, Malaise M, et al. Efficacy and safety of adalimumab as monotherapy in patients with rheumatoid arthritis for whom previous disease modifying antirheumatic drug treatment has failed. Ann Rheum Dis. 2004;63(5):508–16.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    St Clair EW, van der Heijde DM, Smolen JS, et al. Combination of infliximab and methotrexate therapy for early rheumatoid arthritis: A randomized, controlled trial. Arthritis Rheum. 2004;50(11):3432–43.PubMedCrossRefGoogle Scholar
  46. 46.
    Emery P, Breedveld FC, Hall S, et al. Comparison of methotrexate monotherapy with a combination of methotrexate and etanercept in active, early, moderate to severe rheumatoid arthritis (COMET): A randomised, double-blind, parallel treatment trial. Lancet. 2008;372(9636):375–82.PubMedCrossRefGoogle Scholar
  47. 47.•
    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):518–31. A review examining associations of TNF inhibition in RA with the occurrence of CV events.CrossRefGoogle Scholar
  48. 48.
    Weisman MH, Paulus HE, Burch FX, et al. A placebo-controlled, randomized, double-blinded study evaluating the safety of etanercept in patients with rheumatoid arthritis and concomitant comorbid diseases. Rheumatology (Oxford). 2007;46(7):1122–5.CrossRefGoogle Scholar
  49. 49.
    Carmona L, Descalzo MA, Perez-Pampin E, et al. All-cause and cause-specific mortality in rheumatoid arthritis are not greater than expected when treated with tumour necrosis factor antagonists. Ann Rheum Dis. 2007;66(7):880–5.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Jacobsson LT, Turesson C, Gulfe 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):1213–8.PubMedGoogle Scholar
  51. 51.
    Solomon DH, Avorn J, Katz JN, et al. Immunosuppressive medications and hospitalization for cardiovascular events in patients with rheumatoid arthritis. Arthritis Rheum. 2006;54(12):3790–8.PubMedCrossRefGoogle Scholar
  52. 52.
    Nadareishvili Z, Michaud K, Hallenbeck JM, et al. Cardiovascular, rheumatologic, and pharmacologic predictors of stroke in patients with rheumatoid arthritis: A nested, case-control study. Arthritis Rheum. 2008;59(8):1090–6.PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.•
    Bili A, Tang X, Pranesh S, et al. Tumor necrosis factor alpha inhibitor use and decreased risk for incident coronary events in rheumatoid arthritis. Arthritis Care Res (Hoboken). 2014;66(3):355–63. An observational cohort study examining CVD outcomes associated with TNF inhibition in RA compared to CVD outcomes associated with methotrexate and non-methotrexate non-biologic DMARDs.CrossRefGoogle Scholar
  54. 54.
    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):2905–12.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Suissa S, Bernatsky S, Hudson M. Antirheumatic drug use and the risk of acute myocardial infarction. Arthritis Rheum. 2006;55(4):531–6.PubMedCrossRefGoogle Scholar
  56. 56.
    Wolfe F, Michaud K. The risk of myocardial infarction and pharmacologic and nonpharmacologic myocardial infarction predictors in rheumatoid arthritis: A cohort and nested case-control analysis. Arthritis Rheum. 2008;58(9):2612–21.PubMedCrossRefGoogle Scholar
  57. 57.
    Levine B, Kalman J, Mayer L, et al. Elevated circulating levels of tumor necrosis factor in severe chronic heart failure. N Engl J Med. 1990;323(4):236–41.PubMedCrossRefGoogle Scholar
  58. 58.
    Torre-Amione G, Kapadia S, Lee J, et al. Tumor necrosis factor-alpha and tumor necrosis factor receptors in the failing human heart. Circulation. 1996;93(4):704–11.PubMedCrossRefGoogle Scholar
  59. 59.
    Bradham WS, Moe G, Wendt KA, et al. TNF-alpha and myocardial matrix metalloproteinases in heart failure: Relationship to LV remodeling. Am J Physiol Heart Circ Physiol. 2002;282(4):H1288–95.PubMedGoogle Scholar
  60. 60.
    Bradham WS, Bozkurt B, Gunasinghe H, et al. Tumor necrosis factor-alpha and myocardial remodeling in progression of heart failure: A current perspective. Cardiovasc Res. 2002;53(4):822–30.PubMedCrossRefGoogle Scholar
  61. 61.
    Aikawa R, Nitta-Komatsubara Y, Kudoh S, et al. Reactive oxygen species induce cardiomyocyte apoptosis partly through TNF-alpha. Cytokine. 2002;18(4):179–83.PubMedCrossRefGoogle Scholar
  62. 62.
    Kadokami T, Frye C, Lemster B, et al. Anti-tumor necrosis factor-alpha antibody limits heart failure in a transgenic model. Circulation. 2001;104(10):1094–7.PubMedCrossRefGoogle Scholar
  63. 63.
    Kubota T, Bounoutas GS, Miyagishima M, et al. Soluble tumor necrosis factor receptor abrogates myocardial inflammation but not hypertrophy in cytokine-induced cardiomyopathy. Circulation. 2000;101(21):2518–25.PubMedCrossRefGoogle Scholar
  64. 64.
    Bozkurt B, Torre-Amione G, Warren MS, et al. Results of targeted anti-tumor necrosis factor therapy with etanercept (ENBREL) in patients with advanced heart failure. Circulation. 2001;103(8):1044–7.PubMedCrossRefGoogle Scholar
  65. 65.
    Wolfe F, Michaud K. Heart failure in rheumatoid arthritis: Rates, predictors, and the effect of anti-tumor necrosis factor therapy. Am J Med. 2004;116(5):305–11.PubMedCrossRefGoogle Scholar
  66. 66.
    Mann DL, McMurray JJ, Packer M, et al. Targeted anticytokine therapy in patients with chronic heart failure: Results of the randomized etanercept worldwide evaluation (RENEWAL). Circulation. 2004;109(13):1594–602.PubMedCrossRefGoogle Scholar
  67. 67.
    Aderka D, Engelmann H, Maor Y, et al. Stabilization of the bioactivity of tumor necrosis factor by its soluble receptors. J Exp Med. 1992;175(2):323–9.PubMedCrossRefGoogle Scholar
  68. 68.
    Chung ES, Packer M, Lo KH, et al. Anti-TNF therapy against congestive heart failure investigators. randomized, double-blind, placebo-controlled, pilot trial of infliximab, a chimeric monoclonal antibody to tumor necrosis factor-alpha, in patients with moderate-to-severe heart failure: Results of the anti-TNF therapy against congestive heart failure (ATTACH) trial. Circulation. 2003;107(25):3133–40.PubMedCrossRefGoogle Scholar
  69. 69.
    Listing J, Strangfeld A, Kekow J, et al. Does tumor necrosis factor alpha inhibition promote or prevent heart failure in patients with rheumatoid arthritis? Arthritis Rheum. 2008;58(3):667–77.PubMedCrossRefGoogle Scholar
  70. 70.
    Testa M, Yeh M, Lee P, et al. Circulating levels of cytokines and their endogenous modulators in patients with mild to severe congestive heart failure due to coronary artery disease or hypertension. J Am Coll Cardiol. 1996;28(4):964–71.PubMedCrossRefGoogle Scholar
  71. 71.
    Bujak M, Frangogiannis NG. The role of IL-1 in the pathogenesis of heart disease. Arch Immunol Ther Exp (Warsz). 2009;57(3):165–76.CrossRefGoogle Scholar
  72. 72.
    Danesh J, Kaptoge S, Mann AG, et al. Long-term interleukin-6 levels and subsequent risk of coronary heart disease: Two new prospective studies and a systematic review. PLoS Med. 2008;5(4):e78.PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Su D, Li Z, Li X, et al. Association between serum interleukin-6 concentration and mortality in patients with coronary artery disease. Mediat Inflamm. 2013. doi: 10.1155/2013/726178.Google Scholar
  74. 74.
    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):2662–9.PubMedCrossRefGoogle Scholar
  75. 75.
    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):619–28.PubMedCrossRefGoogle Scholar
  76. 76.
    Abbate A, Salloum FN, Vecile E, et al. Anakinra, a recombinant human interleukin-1 receptor antagonist, inhibits apoptosis in experimental acute myocardial infarction. Circulation. 2008;117(20):2670–83.PubMedCrossRefGoogle Scholar
  77. 77.•
    Abbate A, Van Tassell BW, Biondi-Zoccai G, et al. Effects of interleukin-1 blockade with anakinra on adverse cardiac remodeling and heart failure after acute myocardial infarction [from the virginia commonwealth university-anakinra remodeling trial (2) (VCU-ART2) pilot study. Am J Cardiol. 2013;111(10):1394–400. An initial intervention study examining the impact of anakinra on CV outcomes in non-RA patients following myocardial infarction.PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.•
    Van Tassell BW, Arena R, Biondi-Zoccai G, et al. Effects of interleukin-1 blockade with anakinra on aerobic exercise capacity in patients with heart failure and preserved ejection fraction (from the D-HART pilot study). Am J Cardiol. 2014;113(2):321–7. A study on effect of anakinra in heart failure.PubMedCrossRefGoogle Scholar
  79. 79.
    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):734–6.PubMedCrossRefGoogle Scholar
  80. 80.
    McInnes IB, Thompson L, Giles JT, et al. Effect of interleukin-6 receptor blockade on surrogates of vascular risk in rheumatoid arthritis: MEASURE, a randomised, placebo-controlled study. Ann Rheum Dis. 2013. doi: 10.1136/2013/204345.Google Scholar
  81. 81.•
    Schiff MH, Kremer JM, Jahreis A, et al. Integrated safety in tocilizumab clinical trials. Arthritis Res Ther. 2011;13(5):R141. A robust analysis of TCZ safety profile including examinations of CV events.PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    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):1821–4.PubMedCrossRefGoogle Scholar
  83. 83.
    Kerekes G, Soltesz P, Der H, et al. Effects of rituximab treatment on endothelial dysfunction, carotid atherosclerosis, and lipid profile in rheumatoid arthritis. Clin Rheumatol. 2009;28(6):705–10.PubMedCrossRefGoogle Scholar
  84. 84.
    Mathieu S, Pereira B, Dubost JJ, et al. No significant change in arterial stiffness in RA after 6 months and 1 year of rituximab treatment. Rheumatology (Oxford). 2012;51(6):1107–11.CrossRefGoogle Scholar
  85. 85.
    van Vollenhoven RF, Emery P, Bingham 3rd CO, et al. Longterm safety of patients receiving rituximab in rheumatoid arthritis clinical trials. J Rheumatol. 2010;37(3):558–67.PubMedCrossRefGoogle Scholar
  86. 86.
    Passalia C, Minetto P, Arboscello E, et al. Cardiovascular adverse events complicating the administration of rituximab: Report of two cases. Tumori. 2013;99(6):288e–92.PubMedGoogle Scholar
  87. 87.
    Arunprasath P, Gobu P, Dubashi B, et al. Rituximab induced myocardial infarction: A fatal drug reaction. J Cancer Res Ther. 2011;7(3):346–8.PubMedCrossRefGoogle Scholar
  88. 88.
    van Sijl AM, van der Weele W, Nurmohamed MT. Myocardial infarction after rituximab treatment for rheumatoid arthritis: Is there a link? Curr Pharm Des. 2014;20(4):496–9.PubMedCrossRefGoogle Scholar
  89. 89.
    Mathieu S, Couderc M, Glace B, et al. Effects of 6 months of abatacept treatment on aortic stiffness in patients with rheumatoid arthritis. Biol. 2013;7:259–64.Google Scholar
  90. 90.
    Kaur K, Kalra S, Kaushal S. Systematic review of tofacitinib: A new drug for the management of rheumatoid arthritis. Clin Ther. 2014;36(7):1074–86.PubMedCrossRefGoogle Scholar
  91. 91.
    Wolfe F, Michaud K, Li T, et al. Chronic conditions and health problems in rheumatic diseases: comparisons with rheumatoid arthritis, noninflammatory rheumatic disorders, systemic lupus erythematosus, and fibromyalgia. J Rheumatol. 2010;37:305–15.PubMedCrossRefGoogle Scholar
  92. 92.
    Boonen A, Maetzel A, Drummond M, et al. The OMERACT initiative. Towards a reference approach to derive QALY for economic evaluations in rheumatology. J Rheumatol. 2009;36:2045–9.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York (outside the USA) 2014

Authors and Affiliations

  • Debbie T. Lim
    • 1
    • 3
  • Amy C. Cannella
    • 1
    • 3
  • Kaleb D Michaud
    • 1
    • 2
  • Ted R. Mikuls
    • 1
    • 3
    Email author
  1. 1.Division of RheumatologyUniversity of Nebraska Medical CenterOmahaUSA
  2. 2.National Data Bank for Rheumatic DiseasesWichitaUSA
  3. 3.Omaha Veterans Affairs Medical CenterOmahaUSA

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