Dynamics of Modified Cardiovascular Risk Factors in Patients with Rheumatoid Arthritis on the Background of 5-Year Therapy with an Interleukin 6 Receptor Inhibitor.

The effect of an inhibitor of interleukin (IL) 6 receptors on the state of the cardiovascular system in patients with rheumatoid arthritis (RA) remains poorly understood, especially with its long-term use.

The aim: of this work was to study the effect of therapy with the IL-6 receptor inhibitor tocilizumab (TCZ) on the dynamics of modifiable risk factors (RF), total cardiovascular risk (CVR), structural changes in the carotid arteries (CA), and the incidence of cardiovascular complications (CVC) in patients with rheumatoid arthritis during the 260-week follow-up period.

Materials and methods: : The study included 37 patients with active RA (32 women and 5 men) with ineffectiveness and/or intolerance to disease modifying anti-rheumatic drugs (DMARDs); median age was 56 [48; 68] years, disease duration was 92 [49; 158] months; DAS28 (Disease Activity Score 28)-6.2 [5.5; 6.7] points; all patients were seropositive for rheumatoid factor (RF), 86%-for antibodies to cyclic citrullinated peptide (ACCP). Patients received TCZ therapy 8 mg/kg intravenously every 4 weeks; after 192 [176; 210] weeks, 60% of patients switched to subcutaneous administration of the drug at a dose of 162 mg once a week. In 51% of patients with RA, TCZ monotherapy was performed, in 49%-combination therapy of TCZ with DMARDs. Statins were received by 17 (46%) patients, including 7 patients before and 10 after inclusion in the study. All patients underwent an assessment of traditional risk factors, the total cardiovascular risk was calculated using the mSCORE scale, atherosclerotic vascular lesions were assessed by the detection of atherosclerotic plaques (ASP) of CA. The observation period was 260.4 [251.5; 283.4] weeks.

Results: : After 260 weeks of TCZ therapy, RA remission was observed in 32 (86%) patients, low activity-in 5 (14%) patients. During the observation period, the frequency of modified RF and the total CVR did not change significantly, an increase in body mass index (BMI) by 11% was recorded, the number of patients with hypercholesterolemia and a reduced level of HDL cholesterol (C) decreased. In patients without statin therapy, there were no significant changes in the blood lipid spectrum. In the group of patients receiving statins, there was an increase in HDL-CH by 43%, a decrease in cholesterol levels by 15%, atherogenic index (AI) by 56% (p < 0.01 in all cases) and associations between the dynamics of ∆cholesterol and ∆CRP (r = 0.35; p = 0.04), ∆LDL-CH and ∆CRP (r = 0.41; p = 0.03). Significant structural changes in CA in RA patients by the end of  260 weeks of TCZ therapy were not identified. Initially, intima-media thickness (IMT) CA positively moderately correlated with age (r = 0.7; p < 0.01), BMI (r = 0.37; p < 0.01), systolic blood pressure (SBP) (r = 0.62; p < 0.01) and weakly with lipid spectrum parameters-cholesterol (r = 0.29; p < 0.01), LDL-CH (r = 0.36; p < 0.01). No new associations of IMT CA by the end of the observation, as well as the relationship of the IMT CA value with the indicators of RA activity and the ongoing therapy, were identified. By the end of the study, the distribution of patients by mSCORE value and CVR level did not change significantly. The incidence of CVC was 0.54 per 100 patient-years over a 260-week period of TCZ use.

Conclusions: : Against the background of long-term TCZ therapy in RA patients, there was no increase in CVR and significant structural changes in CA. It is necessary to dynamically monitor the blood lipid profile and CVR in RA patients receiving TCZ therapy. Statin therapy can successfully control dyslipidemia in RA patients who receive long-term TCZ.