SAT0132 DOES JANUS KINASE INHIBITION INDUCED HYPERLIPIDAEMIA ASSOCIATE WITH AN INCREASE OF AORTIC STIFFNESS IN PATIENTS WITH ARTHRITIS? PRELIMINARY RESULTS OF A PROSPECTIVE PILOT STUDY ON CARDIOVASCULAR RISK

Abstract

Background:Treatment with Janus Kinase inhibitors (JAK-i) (Tofacitinib, Baricitinib) can cause an increase of serum lipids such as total cholesterol, low- (LDL) and high- (HDL) density lipoproteins in patients with arthritis (1). On the other hand, JAK-i can reduce systemic inflammation and have therefore a beneficial effect on the cardiovascular system of treated patients. However, the effects of JAK-i on the CV system have not been adequately examined. In particular, we are not aware of any ’’real world’’ data concerning CV risk of patients receiving JAK-i treatment.Stiffness of the aortic vasculature is a modifiable, valid and independent surrogate predictor of CV risk and can be measured by carotid femoral pulse wave velocity (cfPWV). Its predicted value has been shown in a series of epidemiological studies and cfPWV is characterized as the gold standard marker for the assessment of aortic stiffness (2)Objectives:Aim of this study was to evaluate for the first time changes of cfPWV, lipid profile and traditional CV risk factors in patients receiving JAK-i therapy.Methods:Measurements of cfPWV, total cholesterol, LDL, HDL and inflammation markers were performed directly before and 5-12 months (median 6.5 months; 5-7, IQR) after initiation of JAK-i therapy. Additionally, traditional CV risk factors such as nicotine, obesity (Body-Mass-Index), diabetes and arterial hypertension were documented for both time points next to clinical activity markers, such as the Disease Activity Score 28 (DAS28). Differences in lipids, DAS28 and inflammation markers between the two time points were examined by paired t-Test. Given the fact that cfPWV can be confounded by mean arterial pressure (MAP), a mixed linear model, with MAP as a covariate, was used in order to test for differences in adjusted cfPWV values between two measurements.Results:29 patients with rheumatoid arthritis (RA) (72.4%,female) with a median age of61.5(51-75, IQR) years and a median DAS28-CRP of5.27(3.62-6.21, IQR) were recruited before (planed) initiation of JAK-i therapy.30.7%of the patients were smokers,38.5%had arterial hypertension and0.4%diabetes. Median BMI was24kg/m2(22-29, IQR).Mean total cholesterol and LDL values increased significantly under treatment with JAK-i (196.76±38.70vs.220.28±40.41mg/dl;p=0.010and119.12±31.88vs.138.72±37.43mg/dl;p=0.032, respectively). Moreover, MAP increased significantly during the same time period (105± 9.82vs.109.91±11.22mmHg; p=0.005). On the other hand, C-reactive protein (CRP) had decreased significantly between the two measurements [15.27(3.82-38.9, IQR) vs.3.82(1.4-15.9) mg/dl;p=0.05]. No statistical significant difference of cfPWV values could be observed under JAK-i treatment[-0,035 95% CI (-0,615 - 0,545); p=0.903].Conclusion:Our results reveal that JAK-i induced hyperlipidaemia did not associate with an increase of a surrogate marker of CV risk, such as aortic stiffness. More data are needed to conclude whether JAK-i could have a (positive or negative) effect on the CV system.An additional examination of the current patients in 12-18 months from treatment initiation and the recruitment of new RA and psoriatic arthritis patients are currently taking place.