Tofacitinib therapy improves disease activity and is associated with the restoration of CD4+ regulatory T cell homeostasis in active Takayasu arteritis: a two-year prospective open-label cohort study

To investigate the efficacy of Tofacitinib (TOF) in patients with active Takayasu Arteritis (TAK), and to explore its effect on CD4 + regulatory T cells (Tregs) homeostasis and its relationship with clinical outcomes. This was a prospective, open-label cohort study. Thirty-four patients with active TAK and 28 healthy controls (HCs) matched for comparable sex and age were recruited. All patients were treated with glucocorticoids (GCs) and TOF. Complete response (CR) was assessed at the sixth month of treatment, and any relapse occurring after achievement of CR was recorded. Patients were followed up for 24 months, during which regular clinical assessments were conducted for inflammatory parameters, GC dose, vascular imaging, flow cytometric analysis of the CD4 + CD25 high FOXP3 + Treg frequency, the proportion of FOXP3 + cells in CD4 + CD25 high T cells, the proportions of IFN-γ + and IL-17 A + subsets among CD4 + CD25 high FOXP3 + T cells in peripheral blood .SPSS 22.0 (SPSS Inc., USA) was used for data analysis. A P-value of less than 0.05 was defined as indicating statistical significance. CR was achieved in 26 out of 34 patients (76.5%) at the six-month endpoint. After six months of TOF therapy, both the mean steroid dosage and the levels of acute-phase reactants decreased significantly.In patients with active TAK, the frequency of CD4 + CD25 high FOXP3 + Tregs and the expression level of FOXP3 in CD4 + CD25 high T cells were reduced, while the frequencies of IFN-γ + CD4 + CD25 high FOXP3 + T cells and IL-17 A + CD4 + CD25 high FOXP3 + T cells increased.The frequencies of IFN-γ + CD4 + CD25 high FOXP3 + T cells and IL-17 A + CD4 + CD25 high FOXP3 + T cells were positively correlated with disease activity parameters. After six months of effective TOF therapy, the frequency of CD4 + CD25 high FOXP3 + Tregs and the expression of FOXP3 in CD4 + CD25 high T cells increased in the CR group, while the percentages of IFN-γ + CD4 + CD25 high FOXP3 + T cells and IL-17 A + CD4 + CD25 high FOXP3 + T cells decreased. These changes remained stable throughout the 24-month follow-up period. TOF effectively induces remission in TAK, particularly in refractory cases, while facilitating GCs tapering and reducing relapse rates. Active TAK is characterized by reduced Treg frequencies and functional impairment, TOF therapy improved TAK disease activity and was associated with the restoration of CD4 + Tregs homeostasis.