Beyond clinical improvement: a pilot study on cytokine and ultrasonographic changes following Tofacitinib treatment in Rheumatoid arthritis

Introduction: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation and progressive joint damage. Interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) contribute to its pathogenesis, while musculoskeletal ultrasound provides valuable information about joint inflammatory activity. The aim of the study was to evaluate changes in IL-1β and IL-6 protein and gene expression and their correlations with clinical and ultrasonographic disease activity in RA patients before and after Tofacitinib treatment. Methods: Fourteen patients with RA were evaluated at baseline and after Tofacitinib treatment. Disease activity was assessed using the 28-joint Disease Activity Score (DAS28) and the seven joint Global Ultrasound Score (GUS7). Plasma cytokine concentrations were measured using enzyme-linked immunosorbent assays (ELISA), and gene expression in peripheral blood cells was assessed by qPCR. Results: After six months, median DAS28 decreased from 5.80 to 3.31 (p<0.001), while GUS7 decreased from 20.0 to 11.0 (p=0.002). Plasma IL-6 concentrations decreased significantly from 7.83 to 0.06 pg/mL (p=0.020). No significant changes were observed in plasma IL-1β concentrations (p=0.445) or IL1-β and IL-6 gene expression (p=0.922 and p=1.0, respectively). DAS28 and GUS7 were positively correlated at baseline (ρ=0.890, p<0.001) and after treatment (r=0.689, p=0.006). Conclusion: Tofacitinib treatment was associated with improved clinical and ultrasonographic disease activity and reduced plasma IL-6 concentrations. The absence of significant changes in IL-1β concentrations and cytokine gene expression highlights the complexity of inflammatory regulation in RA. Combined clinical, imaging, and molecular assessments may provide complementary information on treatment response.