Background Inflammation plays a crucial role in rheumatoid arthritis (RA) pathogenesis. Tocilizumab (TCZ) is effective therapy in RA. One of the leading causes of death in RA is cardiovascular events (CVE). Impact of TCZ on the development of CVE remains unclear. Heart rate variability (HRV) (as indicator of cardiac autonomic neuropathy (CAN)) and blood lipids are recognized as important and independent risk factors for CVE.
Objectives to analyze HRV parameters, blood lipid levels initially and after 6 months of TCZ therapy in RA pts.
Methods 40 RA pts (9 men, 31 women; mean age 49,1±1,8 years old; disease duration 68±9,2 months; mean DAS28 6,69±0,1; IgM RF+ and Anti-CCP+ 85%) were included in the study. Cardiovascular disease has 23/40 RA pts: arterial hypertension 21 (52%), ischemic heart disease 4 (10%) pts. All pts received TCZ 8 mg/kg IV every 4 weeks with moderate/good effect (EULAR). Serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), atherogenic index (AI): (TC-HDL-C)/HDL-C, body mass index (BMI), disease activity score (DAS28), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), IgM RF, Anti-CCP, IL-6, HAQ, pain score (visual analog scale, VAS) were examined. Signs of CAN assessed by time-domain and spectral HRV parameters from 24-hour ECG. All above parameters were examined at baseline and after 24 weeks of TCZ therapy.
Results The higher VAS and level of IgM RF were associated with lower parasympathetic parameters (rMSSD, pNN50, HF) and higher LF/HF at baseline. TCZ therapy resulted in significant increase in levels of all time-domain and spectral HRV parameters (p<0,01). There are also significant increasing of BMI, TC, HDL-C, decreasing of AI (p<0,01) and tendency to decrease of TG levels after TCZ treatment. The levels of CRP, ESR, IgM RF, IL-6 and DAS28, HAQ, VAS have dramatically decreased after TCZ therapy (p<0,01). The rise in parasympathetic (ΔrMSSD, ΔpNN50) and other parameters (ΔMean NN) of HRV was higher in pts with higher VAS at baseline. The rise in ΔpNN50 was also prominent than lower VAS was achieved after TCZ therapy. The rise in parasympathetic (ΔrMSSD, ΔpNN50, ΔHF) and total HRV (ΔSDNN, ΔTP) became lesser as a Rg-stage progressed.
Conclusions Pain intensity negative affects parasympathetic activity, and this action is reversible. Severity of RA (Rg-stage) irreversibly impairs cardiac autonomic neuroregulation. In general, TCZ therapy resulted in significantly increased HRV, improved lipid profile and decrease in RA activity. These changes may suggest that TCZ reduces cardiovascular risk. However, BMI have increased on TCZ therapy. An investigation of long-term effect of TCZ on cardiovascular outcomes is required.
Disclosure of Interest None Declared