Dynamics of traditional modifiable risk factors, total cardiovascular risk, and structural changes of carotid arteries in patients with rheumatoid arthritis on long-term interleukin-6 receptor antagonist treatment

Abstract

The effect of an inhibitor of interleukin-6 (IL-6) receptors on the state of the cardiovascular system in patients with rheumatoid arthritis remains poorly understood.Objective: to study the effect of therapy with an inhibitor of IL-6 receptors, tocilizumab (TCZ), on the dynamics of modifiable risk factors, total cardiovascular risk, and structural changes in the carotid arteries in patients with rheumatoid arthritis during a 12-month follow-up period.Material and methods. The study included 40 patients with active rheumatoid arthritis (33 women and 7 men) with ineffectiveness and/or intolerance to basic anti-inflammatory drugs (DMARDs); the median age was 55 (49; 64) years, the duration of the disease – 102 (48; 162) months; DAS28 – 6.2 (5.5; 6.7) points; all patients were seropositive for rheumatoid factor, 80% – for antibodies to cyclic citrullinated peptide. Patients received TCZ 8 mg/kg therapy every 4 weeks: 52% received TCZ monotherapy, 48% received combined TCZ therapy with DMARDs. All patients underwent an assessment of traditional risk factors, the total cardiovascular risk was calculated using the mSCORE, and atherosclerotic vascular damage was assessed by the detection of atherosclerotic plaques.Results. After 12 months of TCZ therapy, a decrease in disease activity was noted: remission was observed in 25 patients (64%) with rheumatoid arthritis, low disease activity – in 12 (31%); DAS28, HAQ, CRP and ESR concentrations decreased significantly. А high frequency of traditional risk factors was found in rheumatoid arthritis patients: dyslipidemia – 67%, arterial hypertension – 65%, overweight – 55%, burdened heredity for cardiovascular diseases (CVD) – 35%, smoking – 15%. Every third patient had a combination of three or more traditional risk factors. After 12 months of TCZ therapy, the frequency of traditional risk factors did not significantly change, there was an increase in BMI by 2%, an increase in the concentration of HDL-C in serum by 27%, a decrease in the atherogenic index by 28% (p<0.01). Moreover, an increase in the level of HDL-C by the finish was found in patients regardless of statin therapy. Changes in the concentration of other lipids during the observation, including during therapy with statins, were not observed. A negative correlation the dynamics of the levels of ∆HS and ∆CRP (R=−0.37; p<0.05), ∆HS of LDL and ∆CRP (R=−0.42; p<0.01) was found. A very high cardiovascular risk according to the SCORE scale was determined in 78% of patients, moderate – in 2%, and low – in 20% of patients. The distribution of patients by mSCORE value and level of cardiovascular risk were not documented after 12 months of TCZ therapy. No significant structural changes in carotid arteries in rheumatoid arthritis patients were revealed by the end of 12 months of TCZ therapy.Conclusion. After 12 months of TCZ therapy resulted in decreased rheumatoid arthritis activity, increased the level of HDL-C, atherogenic index, BMI; the frequency of traditional risk factors and the total cardiovascular risk did not change. Despite the very high risk of developing CVD associated with the inflammatory activity of rheumatoid arthritis, the accumulation of traditional risk factors and their combination, subclinical atherosclerotic vascular lesions, no significant structural changes in the carotid arteries were found in rheumatoid arthritis patients on TCZ therapy. Insufficient effectiveness of statin therapy was revealed.

Keywords

• interleukin-6 receptor inhibitor
• tocilizumab
• traditional risk factors
• dyslipidemia
• total cardiovascular risk
• score
• atherosclerotic vascular disease