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OBJECTIVE: Tumor necrosis factor (TNF-alpha), a pivotal inflammatory cytokine, is known to induce proatherogenic changes in the lipid profile and may increase the cardiovascular risk of patients with rheumatoid arthritis (RA). We examined the effects of anti-TNF-alpha antibody (infliximab, IFX) compared with methotrexate (MTX) on lipid profiles in patients with RA. METHODS: We selected retrospectively all patients with refractory RA (n = 32) who achieved a successful outcome (DAS-28 score < 2.6) in 6 months with IFX treatment, and control groups of age- and sex-matched patients with active RA treated with MTX and healthy participants. We traced fasting serum levels of total cholesterol (TCHO) and triglyceride (TG) for 6 months and used an online dual enzymatic method for simultaneous quantification of cholesterol (CHO) and TG by high performance liquid chromatography (HPLC). RESULTS: Mean C-reactive protein levels (baseline 4.5) fell to below 1 in 6 months. MTX treatment elevated and normalized TCHO and TG levels. IFX treatment, however, preferentially induced extra-high TG levels. HPLC analyses identified similar CHO profiles between patients treated with IFX or MTX, but IFX selectively induced a huge VLDL-TG peak. Statins successfully controlled these extra-high TG levels. CONCLUSION: In patients successfully treated with IFX or MTX, CHO levels were elevated and normalized, but IFX treatment preferentially induced extra-high levels of VLDL-TG. Thus, there is differential regulation of the lipid profile between IFX and MTX, necessitating careful attention to TG levels with IFX treatment.