Background Immune dysregulation and systemic inflammation are integral to the development of accelerated atheromatosis in rheumatoid arthritis (RA), mediated by various cytokines. Imbalance of haemostasis, as evidenced by increased levels of the fibrinolysis inhibitor plasminogen activator inhibitor-1 (PAI-1) contributes to future risk of cardiovascular diseases. IL-6 is implicated in the pathogenesis of RA, and tocilizumab (TCZ), a humanized monoclonal anti-IL-6 receptor antibody is being used for the treatment of RA. Its metabolic effects on serum adipokine levels, fibrinolysis and insulin sensitivity have not been investigated in detail so far.
Objectives To investigate the metabolic effects of 6-months TCZ treatment of RA patients on serum adipokines and insulin sensitivity.
Methods A total of 19 consecutive patients with RA (18 females, 1 male), aged 48.6±10.9 years (mean±SD, range 25-62), disease duration 10.5±9.3 years (range 2-23) who received 6 infusions of TCZ (8 mg/kg each) monthly for moderate or severe RA (DAS28-ESR>3.2) participated in this study. All medications used before enrolment remained unchanged. Serum levels of IL-6, IL-1b, TNF-α, adiponectin, leptin, resistin, visfatin, and PAI-1, as well as glucose, insulin and cortisone were measured at baseline and 1, 3 and 6 months after treatment. Insulin resistance and sensitivity were assessed by calculation of HOMA-IR and QUICKI index, respectively.
Results As expected, CRP (mean±SD, 17.6±20.3 vs. 2.6±1.5 mg/L) and ESR (50.4±25.4 vs. 11.8±2.2) levels, as well as disease activity index (DAS28-ESR 5.5±1.2 vs. 2.5±1.0) decreased after 6 months of TCZ treatment. Insulin resistance and insulin sensitivity index did not change, despite the fact that body mass index (27.3±7.8 vs. 28.4±8.2 kg/m2) and waist circumference (95.0±17.9 vs. 98.1±18.3 cm) increased significantly. PAI-1 levels significantly decreased from baseline to 6 months (72.5±27.3 vs. 51.0±27.7 pg/ml, p<0.001). There was no difference in PAI-1 decrease between complete responders (DAS28<2.6 at 6 months [n=10 patients]) and the remaining patients. Baseline individual PAI-1 levels were correlated with baseline CRP levels (r=0.6, p=0.08), CRP decline at 6 months (r=0.58, p=0.012) and IL-6 change at 6 months (r=0.48, p=0.04). The other adipokines measured did not demonstrate sustained or statistically significant changes during TCZ treatment.
Conclusions TCZ treatment in patients with RA does not adversely affect insulin sensitivity despite increasing adiposity, but favorably alters PAI-1 levels, thus possibly decreasing cardiovascular risk in these patients.
Disclosure of Interest None Declared