Evaluating the therapeutic potential of tofacitinib in Sjögren's disease: A comprehensive clinical and immunological assessment

Objective To evaluate the efficacy, safety and immunological effects of tofacitinib in patients with Sjögren's disease (SjD), focusing on its impact on disease activity and immune cell modulation. Methods Two independent cohort studies, one retrospective (Cohort I) and one prospective (Cohort II), were conducted to investigate the efficacy of oral tofacitinib treatment in patients diagnosed with SjD. All participants were evaluated for changes in disease activity and lab parameters. Circulating T cells were analysed, focusing on follicular helper T (Tfh) cells and peripheral helper T (Tph) cells. Results In cohort I, 112 patients treated with tofacitinib showed a significant improvement in the ESSDAI score [median (IQR), 8.00 (4.25, 15.75) vs 6.50 (2.25, 12.75), P < 0.001]. In cohort II, ten patients completed the 12-month treatment period. There was a significant reduction in ESSDAI scores at the sixth month compared with baseline (P = 0.001). In total, 80% (8/10) of patients achieved a decrease of at least one point or 15% in ESSPRI scores. A significant reduction in the proportion of Th17 cells was observed (mean ± SD, 14.84 ± 7.70 vs 7.74 ± 4.24, P = 0.008). A decrease in Tfh and Tph cells was also observed, along with decreased pSTAT-3 levels in CD4+ T cells and disease activity scores. No serious adverse events were observed in the two cohorts. Conclusions Tofacitinib effectively improves disease activity and immune regulation in SjD, and it is associated with suppressing Tfh and Tph cells, suggesting its potential as a treatment option. Trial registration ClinicalTrials.gov Identifier: NCT05087589.