Avaliação da função endotelial em pacientes portadores de Artrite Reumatoide antes e após terapia com Tocilizumabe

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects 0.5 to 1% of the population. It is estimated that the risk of cardiovascular death is doubled in patients with RA compared to individuals of the same age and risk factors for atherosclerotic disease. This association is justified, at least in part, by the nature of both inflammatory conditions. The pro-inflammatory property of interleukin-6 seems to have a central role in atherogenesis. In clinical trials with the interleukin 6 receptor blocker (tocilizumab - TCZ) in patients with RA, there was improvement in clinical and laboratory activity of arthritis, but with increased plasma levels of total cholesterol, triglycerides, low density lipoprotein (LDL ) and high density lipoprotein (HDL), a finding with an uncertain prognosis. The main objectives of this study were to evaluate endothelial function and lipid profile of RA patients with moderate or severe disease activity at the beginning and at 16 weeks of therapy with TCZ. This is a prospective observational cohort study evaluating patients older than 18 years, of both genders, with RA, using TCZ or disease modifying antirheumatic drugs (methotrexate-MTX or leflunomide-LEF) (control group). Exclusion criteria were acute coronary syndrome in the last three months, uncontrolled hypertension (SBP> 160 mmHg or DBP ≥110mmHg). The assessment of endothelial function was conducted by measuring flow-mediated dilatation (FMD). Thirty-one patients were included, 17 of which were given monthly infusions of TCZ (8mg / kg) every four weeks, six MTX (15 to 20 mg / week) and eight LEF (20 mg / day). The variation of FMD before the first infusion of TCZ was 3.12% and the sixteenth week was 6.42% (p = 0.03). In the control group, FMD ranged from 2.54% to 4.79% (p = 0.55). In the sixteenth week was observed also a significant increase in median plasma concentrations of total cholesterol (191 - 240 mg/dl p=0.006), LDL (111 - 149 mg/dl p=0.049), TC/HDL ratio (3.29 - 3.56 p=0.039) and triglycerides (80 - 142 mg/dl p=0.001) in the TCZ group. In that same time period, there was no significant change in the control group lipid profile. In conclusion, at the week 16th of TCZ therapy, there is a significant improvement of endothelial function, however, with worsening of the lipid profile. The cardiovascular prognostic significance of these findings, however, is not established.