Background Subclinical atherosclerosis and an increased incidence of cardiovascular diseases have been observed in rheumatoid arthritis (RA). Inflammation and traditional risk factors could be involved in the pathogenesis. Tocilizumab, an inhibitor of the IL6 pathway, decreases inflammation and could thus improve cardiovascular risk. However, this positive effect can be counterbalanced by tocilizumab-induced dyslipidemia.
Objectives To investigate the effects of tocilizumab on markers of subclinical atherosclerosis in active RA.
Methods Subclinical atherosclerosis was assessed by flow mediated dilatation (FMD) and arterial stiffness (i.e. augmentation index AIx and pulse wave velocity PWV), 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. 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 inhibitor treatment, 2 (9%) to rituximab, and 4 (18%) to abatacept, 14 patients received glucocorticoids (7.8 ± 6.4 mg/day). No changes in FMD (N=9 patients) (6.63±4.68 at 6 months 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. DAS28ESR and DAS28CRP 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) and only 12 patients still received glucocorticoids (7.2 ± 4.2 mg/day; p=0.5 vs baseline). 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/hr, 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 a significant increase in hip circumference (99.43±13.14 vs. 96.68±13.99 cm; p=0.02).
Conclusions Our results are consistent with those of McInnes1 who did not find any improvement in arterial compliance after 24 weeks of tocilizumab therapy, but our findings disagree with data reported by Protegorou2 and Kume3 describing an improvement in endothelial function and arterial compliance
Ann Rheum Dis 2013, doi:10.1136annrheumdis-2013-204345
J Rheumatol. 2011;38:2169-71.
Acknowledgements This study was conducted with a grant from the French National Clinical Research Program (PHRC) and and a grant from Roche Ltd France.
Disclosure of Interest None declared