Proinflammatory cytokines in rheumatoid arthritis: dynamics against therapy with Janus kinase and interleukin 6 inhibitors

Abstract

Increased production of proinflammatory cytokines in serum and synovial fluid plays an important role in the pathogenesis of RA. JAK inhibitors and bDMARD are aimed at suppressing various pathological reactions caused by them.The aim of the study. To determine the effect of therapy with JAK and IL-6 inhibitors on the concentration of proinflammatory cytokines in RA patients in real clinical practice.Materials and methods. The study included 30 patients with a reliable diagnosis of RA, advanced stage of disease, with moderate or high RA activity and ineffectiveness of previous therapy with csDMARD or bDMARD for at least 6 months. 10 patients received TOFA at a dose of 5 mg twice daily 10 received UPA at a dose of 15 mg once daily and 10 were on OKZ therapy at a dose of 64 mg subcutaneously every 4 weeks. Studies were performed before treatment, after 3 and 6 months of therapy. The levels of IL-1β, IL-6, IL-17A, IL-17F, IL-23, IL-31, IL-33, INF-γ, TNF-α in serum were investigated using multiplex xMAR technology on Bio-PlexTM 200 System analyser (BIO-RAD, USA).Results. In all groups of patients after 3 and 6 months from the start of therapy, there was a significant decrease in the RA activity index compared to baseline values. The concentration of IL-1β, IL-17A, IL-17F and IL-23 did not change significantly during treatment with any of the drugs. IL-6 values on TOFA background significantly decreased after 3 and 6 months of follow-up compared to the baseline level. UPA therapy had no effect on IL-6 level during the whole observation period, and against the background of OKZ application its values significantly increased after 3 months, and after 6 months – decreased, remaining higher than the initial values. The concentration of IL-31 after 3 months of TOFA treatment significantly decreased (respectively: 6.95 (3.85; 17.72) pg/ml and 3.00 (1.50; 3.85) pg/ml, p<0.05), and after 6 months – increased, but remained lower than baseline (5.09 (3.85; 6.33) pg/ml, p<0.05). IL-33 level on the background of UPA decreased and after 6 months was significantly lower than baseline (1.11 (0.86; 3.95) pg/ ml; 1.05 (0.37; 3.95) and 0.37 (0.12; 1.23) pg/ml, p<0.05). The concentration of INF-γ after 3 and 6 months of TOFA administration decreased significantly compared to the start of therapy (2.05 (1.48; 3.19) pg/ml; 0.99 (0.49; 2.05) pg/ml and 0.99 (0.49; 2.62) pg/ml, p<0.05). Treatment with OKZ resulted in increased TNF-α levels after 6 months compared to baseline values of 0.79 (0.41; 0.98) pg/ml and 1.23 (0.67; 2.06) pg/ml, p<0.05.Conclusions. The use of TOFA, UPA and OKZ in RA patients has a positive effect on disease activity, but has different effects on the level of proinflammatory cytokines in serum.