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We read with the great interest the paper by Garces et al. Anti-tumour necrosis factor agents and lipid profile: a class effect?  In this study the investigators showed the different effect on lipid profile between infliximab and etanercept in patient with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA). We would like to present the similar study in RA patients treate...
We read with the great interest the paper by Garces et al. Anti-tumour necrosis factor agents and lipid profile: a class effect?  In this study the investigators showed the different effect on lipid profile between infliximab and etanercept in patient with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA). We would like to present the similar study in RA patients treated with infliximab and etanercept. We recruited 38 women, age matched with active RA to the study. The total plasma cholesterol, HDL, LDL and TG levels were measured before and after 12 months of treatment with both TNF-&[alpha] inhibitors. The results are summarized in table 1.
We did not observe any statistically significant changes in the lipid profile after 12 months of therapy with etanercept, however the TG levels after 12 months of treatment had the tendency to decrease. The patients treated with infliximab had at 12 months of the treatment. the statistically significant lower HDL level (p=0,003) and higher TG level (p=0,03) than at baseline. Reduction of HDL and elevation of TG levels was for the first time observed by Cauza et al  after 6 weeks of therapy with infliximab in patients with RA and PsA, that it is in agreement with results of our study. Popa et al.  showed that the long-term therapy of infliximab can lead to pro-atherogenic pattern of the plasma lipids concentration. Seriolo et al.  observed a group of 22 patients with RA treated with etanercept. After 48 week of the treatment the investigators did not observe any significant changes in lipid levels as compared to the baseline. In our study the final HDL level was lower than in the baseline and the TG level was higher than the baseline respectively. The reason of this changes is not fully elucidated. We may speculate that the changes in cholesterol levels in patients with RA treated with TNF-&[alpha] inhibitors may be caused by the influence of this drugs on cytokines network and the adipocytokines. It is known, that the one of adipocytokines – adiponectin has a stream on insulin resistance and lipids metabolism. Low level of adiponectin correlates negatively with low HDL and positively with high TG level.  Recently we published the brief report on increased adiponectin levels in patient with RA treated with etanercept.  The serum HDL and TG levels remained unchanged during the 3 month study. That may suggest differences in lipid influence between infliximab and etanercept. In the recently published study of Gonzalez-Gay et al.  the investigators didn't observed changes in adiponectin levels upon infliximab therapy. The adiponectin concentration partially negatively correlated with TG/HDL ratio, TC/HDL ratio and high fasting plasma glucose levels, and was independent of CRP (C-reactive protein) levels and BMI (body mass index). It is especially important in the light of the results of the study suggesting changes in lipid profile toward pro-atherogenic reduction of HDL after treatment with infliximab. This changes perhaps have no impact on gross cardiovascular risk in patients with RA and effective suppression of inflammation contributes significantly to reduction of cardiovascular risk.
1. Garces SP, Parreira Santos MJ, Vinagre FMR, Roque RM, da Silva JAC: Anti-tumour necrosis factor agents and lipid profile: a class effect? Ann Rheum Dis 2008;67:893-4.
2. Cauza E, Cauza K, Hanusch-Enserer U, Etemad M, Dunky A, Kostner K. Intravenous anti-TNF-alpha therapy leads to elevated triglyceride and reduced HDL-cholesterol levels in patients with rheumatoid arthritis and psoriatic arthritis. Wien Klin Wochenschr 2002;30:1004-7.
3. Popa C, van den Hoogen FHJ, Radstake TRD, Netea MG, Eijsbouts AE, den Heijer M et al. Modulation of lipoprotein plasma concentrations during long-term anti-TNF therapy in patients with active rheumatoid arthritis. Ann Rheum Dis 2007;66:1503-7.
4. Seriolo B, Paolino S, Ferrone C, Cutolo M. Long-term effects of etanercept treatment on lipid profile in patients with rheumatoid arthritis. Ann Rheum Dis 2007 http://ard.bmj.com/cgi/eletters/66/7/958#921:22 Oct 2007.
5. Yamamoto Y, Hirose H, Saito I, Tomita M, Taniyama M, Matsubara K et al. Correlation of the adipocyte-derived protein adiponectin with insulin resistance index and serum high-density lipoprotein-cholesterol, independent of body mass index, in the Japanese population. Clin Sci 2002;103:137-42.
6. Lewicki M, Kotyla P, Kucharz E. Etanercept increases adiponectin level in woman with rheumatoid arthritis. Clin Rheumatol 2008;27:1337-8.
7. Gonzalez-Gay MA, Llorca J, Garcia-Unzueta MT,
Gonzalez-Juanatey C, De Matias JM, Martin J et al. High-grade inflammation, circulatin adiponectin concentrations and cardiovascular risk factors in severe rheumatoid arthritis. Clin Exp Rheumatol 2008;26:596-603.
Table 1 The serum TC (total cholesterol), HDL (high density lipoprotein), LDL (low density lipoprotein) and TG (triglycerides) levels in patients with RA treated with infliximab and etanercept before and after 12 month of therapy