Tofacitinib improves disease activity and immune modulation in Sjogren's syndrome

Tofacitinib (Tofacitinib) is an oral Janus kinase (JAK) inhibitor that has shown good results in the treatment of autoimmune diseases in recent years. Especially in patients with Sjögren's syndrome (SjD), its application potential has gradually received attention. A research summary on the efficacy, safety and immunomodulatory effects of tofacitinib in Sjögren's syndrome was published in March 2025, providing important clinical data and immunological evaluation.

This retrospective and prospective study conducted by the research team is very rigorous in design and aims to comprehensively evaluate the impact of tofacitinib in patients with Sjögren's syndrome. The study is divided into two cohorts: Cohort I is a retrospective study, including 112 patients treated with tofacitinib, and Cohort II is a prospective study, involving 10 patients, to observe changes in disease activity and adjustments in immune parameters during the 12-month treatment process. By assessing the disease activity of all participants, the research team analyzed changes in follicular helper T cells (Tfh) and peripheral helper T cells (Tph) in circulating T cells, providing basic data for understanding the mechanism of action of tofacitinib.

In the results from CohortI, ESSDAI scores improved significantly among 112 patients treated with tofacitinib. Specifically, the median ESSDAI scores before and after treatment were 8.00 (interquartile range [IQR]: 4.25-15.75) and 6.50 (IQR: 2.25-12.75) respectively. Statistical analysis showed that the P value was less than 0.001, indicating that the difference was highly significant. This result demonstrates the effectiveness of tofacitinib in reducing disease activity in patients.

Further analysis of the prospective study results of CohortII showed that after completing 12 months of treatment, the ESSDAI score of 10 patients also decreased significantly at 6 months, with a P value of 0.001, which further supports the positive effect of tofacitinib on Sjögren's syndrome. Of note, 80% (8/10) of these 10 patients had a decrease in ESSPRI score of at least 1 point or 15%, indicating that their subjective symptoms also improved.

From an immunological perspective, the study also found that after treatment with tofacitinib, the number of Th17 cells decreased significantly, with the average value decreasing from 14.84±7.70 to 7.74±4.24, with a P value of 0.008. This change suggests that tofacitinib may inhibitTh17 cell activity to improve the pathological state of Sjögren's syndrome. In addition, the levels of Tfh and Tph cells in CD4+ T cells were also significantly reduced, the expression level of pSTAT-3 was reduced, and the disease activity was subsequently reduced. These results indicate that the effect of tofacitinib is not only reflected in the improvement of clinical symptoms, but also affects the development process of the disease by regulating the activity and number of specific immune cells.

More importantly, no serious adverse events (AE) were reported throughout the study, demonstrating that tofacitinib has a good safety profile in the treatment of Sjogren's syndrome. This result provides strong support for the clinical application of tofacitinib in the treatment of patients with Sjogren's syndrome, because the safety of the drug is one of the important indicators for evaluating its clinical application value.

Based on the above results, the researchers concluded that tofacitinib can effectively improve disease activity in patients with Sjögren's syndrome and exert its effect through immune regulatory mechanisms, especially the inhibition of follicular helper T cells (Tfh) and peripheral helper T cells (Tph). This study provides a scientific basis for the potential of tofacitinib as a new treatment option for Sjögren's syndrome, and is expected to be more widely used in clinical practice in the future.

References:https://www.physiciansweekly.com/tofacitinib-improves-disease-activity-and-immune-regulation-in-sjogrens-disease/