Abstract
Increased cardiovascular mortality has been associated with rheumatoid arthritis (RA). There have been reports indicating that tumor necrosis factor blockers may exert favorable but transient effects on lipid profile, flow-mediated vasodilation (FMD) of the brachial artery, and common carotid intima–media thickness (ccIMT) in RA. In this study, we assessed the effects of rituximab on FMD, ccIMT, and lipid profile. Five female RA patients received two infusions of 1000 mg rituximab i.v. High-resolution B-mode ultrasound was used to assess brachial FMD and ccIMT. We also determined plasma total cholesterol (TC), HDL-C, LDL-C, and triglyceride (Tg) levels. Assessments were performed at baseline, as well as at weeks 2, 6, and 16 after the first infusion. Rituximab (RTX) treatment resulted in a rapid and sustained improvement in FMD. The mean improvement was 30%, 22%, and 81% at weeks 2, 6, and 16, respectively. RTX had little effect on atherosclerosis within this short period of time; however, we observed 10%, 9%, and 2% decreases in ccIMT at weeks 2, 6, and 16, respectively. RTX therapy resulted in 3–11% decrease in TC, as well as 14–35% increase in HDL-C levels. Two infusions of RTX exerted early and sustained favorable effects on endothelial dysfunction, as well as plasma TC and HDL-C levels. RTX may also decrease ccIMT; however, longer follow-up is needed to assess the prolonged effects of RTX on vascular function and lipid profile in RA patients.
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Kerekes G, Szekanecz Z, Dér H, Sándor Z, Lakos G, Muszbek L, Csipő I, Sipka S, Seres I, Paragh G, Kappelmayer J, Szomják E, Veres K, Szegedi G, Shoenfeld Y, Soltész P (2008) Endothelial dysfunction and atherosclerosis in rheumatoid arthritis: a multiparametric analysis using imaging techniques and laboratory markers of inflammation and autoimmunity. J Rheumatol 35(3):398–406
Giles JT, Post W, Blumenthal RS, Bathon JM (2006) Therapy insight: managing cardiovascular risk in patients with rheumatoid arthritis. Nature Clin Pract Rheumatol 2:320–329
Shoenfeld Y, Gerli R, Doria A, Matsuura E, Matucci-Cerinic M, Ronda N, Jara LJ, Abu-Shakra M, Meroni PL, Sherer Y (2005) Accelerated atherosclerosis in autoimmune rheumatic diseases. Circulation 112:3337–3347
Szekanecz Z, Kerekes G, Dér H, Sándor Z, Szabó Z, Végvári A, Simkovics E, Soós L, Szentpétery Á, Besenyei T, Szűcs G, Szántó S, Tamási L, Szegedi G, Shoenfeld Y, Soltész P (2007) Accelerated atherosclerosis in rheumatoid arthritis. Ann N Y Acad Sci 1108:349–358
Ross R (1999) Atherosclerosis—an inflammatory disease. N Engl J Med 340:115–126
Bergholm R, Leirisalo-Repo M, Vehkavaara S, Makimattila S, Taskinen MR, Yki-Jarvinen H (2002) Impaired responsiveness to NO in newly diagnosed patients with rheumatoid arthritis. Arterioscler Thromb Vasc Biol 22:1637–1641
Peters MJ, Symmons DPM, McCarey DW, Nurmohamed MT (2008) Cardiovascular risk management in patients with rheumatoid arthritis and other types of inflammatory arthritis: a EULAR task force. Arthritis Rheum 58(9 Suppl):S421
Bilsborough W, Keen H, Taylor A, O’Driscoll GJ, Arnolda L, Green DJ (2006) Anti-tumour necrosis factor-α therapy over conventional therapy improves endothelial function in adults with rheumatoid arthritis. Rheumatol Int 26:1125–1131
Hürlimann D, Forster A, Noll G, Enseleit F, Chenevard R, Distler O, Béchir M, Spieker LE, Neidhert M, Michel BA, Gay RE, Lüscher TF, Gay S, Ruschitzka F (2002) Anti-tumor necrosis factor-α treatment improves endothelial function in patients with rheumatoid arthritis. Circulation 106:2184–2187
Gonzalez-Juanatey C, Testa A, Garcia-Castelo A, Garcia-Porrua C, Llorca J, Gonzalez-Gay MA (2004) Active but transient improvement of endothelial function in rheumatoid arthritis patients undergoing long-term treatment with anti-tumor necrosis factor α antibody. Arthritis Rheum 51:447–450
Bosello S, Santoliquido A, Zoli A, Di Campli C, Flore R, Tondi P, Ferraccioli G (2008) TNF-α blockade induces a reversible but transient effect of endothelial dysfunction in patients with long-standing severe rheumatoid arthritis. Clin Rheumatol 27:833–839
Del Porto F, Lagana B, Lai S, Nofroni I, Tinti F, Vitale M, Podesta E, Mitterhofer AP, D’Amelio R (2007) Response to anti-tumour necrosis factor α blockade is associated with reduction of carotid intima–media thickness in patients with active rheumatoid arthritis. Rheumatology 46:1111–1115
Vis M, Nurmohamed MT, Wolbink G, Voskuyl AE, de Koning M, van de Stadt R, Twisk JW, Dijkmans BA, Lems WF (2005) Short term effects of infliximab on the lipid profile in patients with rheumatoid arthritis. J Rheumatol 32:252–255
Kiortsis DN, Mavridis AK, Filippatos TD, Vasakos S, Nikas SN, Drosos AA (2006) Effects of infliximab treatment on lipoprotein profile in patients with rheumatoid arthritis and ankylosing spondylitis. J Rheumatol 33:921–923
Soubrier M, Jouanel P, Mathieu S, Poujol D, Claus D, Dubost JJ, Ristori JM (2008) Effects of anti-tumor necrosis factor therapy on lipid profile in patients with rheumatoid arthritis. Jt Bone Spine 75:22–24
Oguz FM, Oguz A, Uzunlulu M (2007) The effect of infliximab treatment on insulin resistance in patients with rheumatoid arthritis. Acta Clin Belg 62:218–222
Gonzalez-Juanatey C, Llorca J, Vazquez-Rodriguez TR, Diaz-Varela N, Garcia-Quiroga H, Gonzalez-Gay MA (2008) Short-term improvement of endothelial function in rituximab-treated rheumatoid arthritis patients refractory to tumor necrosis factor α blocker therapy. Arthritis Rheum 59:1821–1824
Rouster-Stevens KA, Gursahaney A, Ngai KL, Daru JA, Pachman LM (2008) Pharmacokinetic study of oral prednisolone compared with intravenous methylprednisolone in patients with juvenile dermatomyositis. Arthritis Rheum 59:222–226
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This work was supported by research grants T 048541 (Z. S.) and a Bolyai Research Grant (P.S.).
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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 28, 705–710 (2009). https://doi.org/10.1007/s10067-009-1095-1
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DOI: https://doi.org/10.1007/s10067-009-1095-1