Abstract
We investigated the effects of anti-IL-6 receptor antibody, tocilizumab (TCZ), on lipid metabolism. Nineteen patients with rheumatoid arthritis (RA), entered in clinical case–control study of SAMURAI trial at Sasebo Chuo Hospital, were examined. Nine patients received TCZ monotherapy at 8 mg/kg intravenously every 4 weeks (TCZ group) and 10 patients received conventional DMARDs (control group). Serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), apolipoprotein (Apo) A-1, Apo A-2 and Apo B as well as disease activity score (DAS), C-reactive protein and serum amyloid A protein were examined at baseline and after 3 months of the treatment. IL-6 inversely was correlated with LDL, Apo A-1 and Apo A-2, and also tended to correlate with Apo B. In TCZ group, serum levels of TC, HDL, LDL, Apo A-1 and Apo A-2 were significantly increased after 3 months treatment with TCZ. There was no significant change in Apo B, the atherogenic index, and TC/HDL by the TCZ treatment. Changes in the DAS28-ESR negatively correlated with those in TC. In one patient, whose serum level of TCZ was not detected after 3 months of the treatment, the absence of the increment in serum levels of Apo A-1 and A-2 in the patient was remarkable. All of the markers did not change during 3 months in control group. These data may raise an important issue to evaluate the impact of these alternations in lipid metabolism for longer periods in RA patients treated with TCZ.
Similar content being viewed by others
Abbreviations
- Apo:
-
Apolipoprotein
- CRP:
-
C-reactive protein
- DAS:
-
Disease activity score
- DMARDs:
-
Disease-modifying anti-rheumatic drugs
- ESR:
-
Erythrocyte sedimentation rate
- HDL:
-
High-density lipoprotein
- IL-6:
-
Interleukin-6
- LDL:
-
Low-density lipoprotein
- RA:
-
Rheumatoid arthritis
- SAA:
-
Serum amyloid A
- TCZ:
-
Tocilizumab
- TC:
-
Total cholesterol
- TG:
-
Triglyceride
- TNF:
-
Tumor necrosis factor
References
Choy EH, Isenberg DA, Garrood T, Farrow S, Ioannou Y, Bird H et al (2002) Therapeutic benefit of blocking interleukin-6 activity with an anti-interleukin-6 receptor monoclonal antibody in rheumatoid arthritis: a randomized, double-blind, placebo-controlled, dose-escalation trial. Arthritis Rheum 46:3143–3150
Papanicolaou DA, Wilder RL, Manolagas SC, Chrousos GP et al (1998) The pathophysiologic roles of interleukin-6 in human disease. Ann Intern Med 128:127–137
Ganter U, Arcone R, Toniatti C, Morrone G, Ciliberto G (1989) Dual control of C-reactive protein gene expression by interleukin-1 and interleukin-6. EMBO J 8:3773–3779
Ettinger WH, Varma VK, Sorci-Thomas M, Parks JS, Sigmon RC, Smith TK et al (1994) Cytokines decrease apolipoprotein accumulation in medium from Hep G2 cells. Arterioscler Thromb 14:8–13
Sun WH, Binkley N, Bidwell DW, Ershler WB (1993) The influence of recombinant human interleukin-6 on blood and immune parameters in middle-aged and old rhesus monkeys. Lymphokine Cytokine Res 12:449–455
Nishimoto N, Yoshizaki K, Maeda K, Kuritani T, Deguchi H, Sato B et al (2003) Toxicity, pharmacokinetics, and dose-finding study of repetitive treatment with the humanized anti-interleukin 6 receptor antibody MRA in rheumatoid arthritis. Phase I/II clinical study. J Rheumatol 30:1426–1435
Wolfe F, Mitchell DM, Sibley JT, Fries JF, Bloch DA, Williams CA et al (1994) The mortality of rheumatoid arthritis. Arthritis Rheum 37:481–494
Aviña-Zubieta JA, Choi HK, Sadatsafavi M, Etminan M, Esdaile JM, Lacaille D (2008) Risk of cardiovascular mortality in patients with rheumatoid arthritis: a meta-analysis of observational studies. Arthritis Rheum 59:1690–1697
Sattar N, McCarey DW, Capell H, McInnes IB (2003) Explaining how “high-grade” systemic inflammation accelerates vascular risk in rheumatoid arthritis. Circulation 108:2957–2963
Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS et al (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315–324
Nishimoto N, Hashimoto J, Miyasaka N, Yamamoto K, Kawai S, Takeuchi T et al (2007) Study of active controlled monotherapy used for rheumatoid arthritis, an IL-6 inhibitor (SAMURAI): evidence of clinical and radiographic benefit from an X-ray reader-blinded randomised controlled trial of tocilizumab. Ann Rheum Dis 66:1162–1167
Choi HK, Seeger JD (2005) Lipid profiles among US elderly with untreated rheumatoid arthritis—the Third National Health and Nutrition Examination Survey. J Rheumatol 32:2311–2316
Mayer P, Geissler K, Valent P, Ceska M, Bettelheim P, Liehl E (1991) Recombinant human interleukin 6 is a potent inducer of the acute phase response and elevates the blood platelets in nonhuman primates. Exp Hematol 19:688–696
Dixon WG, Watson KD, Lunt M, Hyrich KL, Silman AJ, Symmons DP (2007) 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 56:2905–2912
Jacobsson LT, Turesson C, Nilsson JA, Petersson IF, Lindqvist E, Saxne T et al (2007) Treatment with TNF blockers and mortality risk in patients with rheumatoid arthritis. Ann Rheum Dis 66:670–675
Wijbrandts CA, van Leuven SI, Boom HD, Gerlag DM, Stroes ES, Kastelein JJ et al (2008) Sustained changes in lipid profile and macrophage migration inhibitory factor (MIF) levels after anti-TNF therapy in rheumatoid arthritis. Ann Rheum Dis 68:1316–1321
Peters MJ, Vis M, van Halm VP, Wolbink GJ, Voskuyl AE, Lems WF et al (2007) Changes in lipid profile during infliximab and corticosteroid treatment in rheumatoid arthritis. Ann Rheum Dis 66:958–961
Spanakis E, Sidiropoulos P, Papadakis J, Ganotakis E, Katsikas G, Karvounaris S et al (2006) Modest but sustained increase of serum high density lipoprotein cholesterol levels in patients with inflammatory arthritides treated with infliximab. J Rheumatol 33:2440–2446
Seriolo B, Paolino S, Sulli A, Fasciolo D, Cutolo M (2006) Effects of anti-TNF-alpha treatment on lipid profile in patients with active rheumatoid arthritis. Ann N Y Acad Sci 1069:414–419
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (2001) Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 285:2486–2497
Montecucco F (2009) Mach F (2007) Common inflammatory mediators orchestrate pathophysiological processes in rheumatoid arthritis and atherosclerosis. Rheumatology (Oxford) 48:11–22
Szekanecz Z, Kerekes G, Dér H, Sándor Z, Szabó Z, Végvári A et al (2007) Accelerated atherosclerosis in rheumatoid arthritis. Ann N Y Acad Sci 1108:349–358
Dessein PH, Joffe BI, Singh S (2005) Biomarkers of endothelial dysfunction, cardiovascular risk factors and atherosclerosis in rheumatoid arthritis. Arthritis Res Ther 7:R634–R643
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kawashiri, Sy., Kawakami, A., Yamasaki, S. et al. Effects of the anti-interleukin-6 receptor antibody, tocilizumab, on serum lipid levels in patients with rheumatoid arthritis. Rheumatol Int 31, 451–456 (2011). https://doi.org/10.1007/s00296-009-1303-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00296-009-1303-y