Background/Purpose:  Increased incidence of cardiovascular diseases and sub-clinical atherosclerosis have been observed in rheumatoid arthritis (RA). Inflammation and  traditional risk factors could be involved in the pathogenesis. As Tocilizumab inhibits the IL6 pathway, it decreases inflammation and then could improved the  cardiovascular risk. However, this positive effect could be counterbalanced by the induced dyslipidemia. Objectives: To investigate the effects of Tocilizumab treatment on flow mediated dilatation (FMD) and arterial stiffness (i.e augmentation index AIx and pulse wave velocity PWV), two markers of sub-clinical atherosclerosis in active RA.

Methods:  Sub-clinical atherosclerosis was assessed in 22 RA patients at baseline and after 24 weeks of Tocilizumab therapy.

Results:  22 RA patients, including 18 women (81%) with a mean age of 58.2 ± 11.6 years were included. Of these 22 patients, 18 (81%) had positive rheumatoid factors, 16 (72%) had positive anti-CCP antibodies, 20 (90%) were erosive. 18 patients (81%) were refractory to TNF alpha inhibitors treatments, 2 (9%) to rituximab treatment, 4 (18%) to abatacept treatment. No changes in FMD (N = 9 patients) (6,63±4,68 at 6 month vs. 5,21±2,54 at baseline, p=0,59) or arterial stiffness (N = 22) (PWV: 7,95±3,59 vs. 7,96±2,98, p=0,93; AlX: 29,57±11,7 vs. 29,89±12,83, p=0,92) were detected after 6 months of treatment with Tocilizumab. DAS28 ESR and DAS28 CRP were significantly improved (2,67±1,1 vs. 5,03±0,84, p<0,001 and 3,11±0,95 vs. 4,78±0,66, p<0,001, respectively). Among the DAS28 parameters, a significant improvement in patient global score (41,33±25,88 vs. 64,18±15,29, p=0,003), and number of tender and swollen joints (respectively 4,54±6,42 vs. 7,63±5,63, p=0,01 and 2,5±2,61 vs. 6,63±4,47, p<0,001) was observed. After 6 months of Tocilizumab therapy, CRP (4,28±8,98 vs. 23,93±32,20 mg/l, p=0,015)  and ESR (4,19±3,02 vs. 29,19±24,12 mm/h, p<0.001) significantly decreased. There was no change in systolic and diastolic blood pressure (SBP: 130.79±17.21 vs 131.32±22.96 mm Hg; p=0.87 / DBP: 78.47±11.58 vs 74±12.29 mm Hg; p=0.16). Total cholesterol (2,26±0,45 vs. 1,97±0,48 g/l, p<0,001), LDL cholesterol (1,66±0,4 vs. 1,13±0,30 g/l, p=0,004), atherogenic index (3,62±1,18 vs. 3,07±1,11, p=0,026) and triglycerides (1,22±0,61 vs 1,04±0,48 g/l, p = 0,047) were significantly increased whereas no significant modification in HDL cholesterol (0,66±0,19 vs. 0,71±0,26 g/l, p=0,40) was detected. There was significant increase in hip circumference (99,43±13.14 vs. 96,68±13,99 cm ; p=0,02).

Conclusion:  Unlike Protogerou¹ and Kume², our results suggest that sub-clinical atherosclerosis observed in RA, was not improved after 6 months of Tocilizumab therapy. This lack of improvement might be due to the induced proatherogenic lipid profile. Further studies are needed.

1. Protogerou AD, et al. Atherosclerosis. 2011;219:734-6.
2. Kume K et al. J Rheumatol. 2011;38:2169-71.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/assessment-of-subclinical-atherosclerosis-flow-mediated-dilatation-and-arterial-stiffness-after-24-weeks-of-a-tocilizumab-therapy-in-22-patients-with-rheumatoid-arthritis/