Vasoprotective Effects of Genetically Engineered Biologic Drugs in Patients with Rheumatoid Arthritis

Abstract

The aim of the investigation was to evaluate the impact of genetically engineered biologic drugs (gEBD) -infliximab and rituximab -on endothelium functional state in patients with rheumatoid arthritis (RA) without any concomitant cardiovascular diseases.Materials and Мethods. The study involved 77 patients with RA aged from 18 to 50. The patients matched ACR (1987) or ACR/EuLAR (2010) classification criteria, had no concomitant cardiovascular diseases, and had at least a two-year RA history. Based on the immunological subtype and the type of therapeutic intervention, the patients were divided into 4 groups. We assessed vasomotor endothelial function at micro-and macrocirculatory levels using AngioScan-01 device (AngioScan-Electronics, Russia) before treatment and after 12 months of treatment.Results. RA patients were found to have the signs of endothelial dysfunction in micro-and macrocirculatory vasculature, being more prominent in RF/CCPA-positive (rheumatoid factor/cyclic citrullinated peptide antibodies) disease subtype. Endothelial dysfunction manifestations included the decrease of occlusion index in amplitude and the value of phase shift between the channels after a reactive hyperemia test; the values of these parameters correlating to RA duration, DAS 28 (disease activity score), rheumatoid factor level and CCPA concentration. The use of genetically engineered biologic drugs in RA patients was accompanied by a significant decrease of DAS 28 index, as well as by the reduction of endothelial vasomotor dysfunction signs. Both groups of RF/CCPA-negative patients, regardless of a therapeutic intervention type, were found to have the increase of occlusion index in amplitude up to the control values; as compared with the baseline values, the phase shift between the channels increased on average by 1.5 times (p=0.008) during infliximab use, and during rituximab treatment it grew by 1.6 times (p=0.024). In RF/CCPA-positive RA occlusion index in amplitude increased by 23.5% (p=0.005) after infliximab therapy and by 48.8% (p=0.001) during rituximab treatment; the value of phase shift between the channels increased on average by 1.3 times (p=0.028) in RA patients receiving infliximab, while in a group of patients taking rituximab this value was no different from that in the control group.Conclusion. genetically engineered biologic drug therapy, along with its high anti-inflammatory activity, produces a vasoprotective effect characterized by improved endothelial functional state in the system of small resistive vessels as well as in large muscular arteries. The higher activity of rituximab endothelial protective effect is achieved in RF/CCPA-positive disease subtype, and the use of infliximab has the greater effect on endothelial function in RF/CCPA-negative RA.

The effect of non-TNF-targeted biologics on vascular dysfunction in rheumatoid arthritis: A systematic literature review

“…After 12 months, both groups of patients showed an increase of occlusion index in amplitude up to the control values; as compared with the baseline values, the phase shift between the channels increased on average by 1.6 times (p = 0.0024) during treatment with rituximab. The occlusion index in amplitude increased by 23.5% by 48.8% (p = 0.001) during rituximab treatment [42].…”

“…In the observational study by Meshcherina et al [42], vasomotor endothelial function was evaluated by a proprietary photoplethysmography device (AngioScan-01, AngioScan-Electronics, Russia), before and after 12 months of treatment with rituximab in 77 RA patients of which 39 treated with rituximab. The authors analyzed separately seropositive and seronegative patients: the first group consisted of 22 patients with median age of 40.1 years (36.8-47.3), the second group comprised 17 patients with median age of 34.5 years (28.1-48.5).…”