Tofacitinib Treatment for Active Dermatomyositis and Anti-synthetase Syndrome: A Prospective Cohort Pilot Study

Abstract Objectives The objective of this study was to evaluate the efficacy and safety of tofacitinib in the treatment of active dermatomyositis (DM) and anti-synthetase syndrome (ASS). Methods Tofacitinib was administered at a dose of 5 mg twice daily to patients who exhibited inadequate response to conventional treatments. The primary end point was the reduction of T follicular helper (Tfh) cells at week 24. Key secondary endpoints included clinical scores. Moreover, we analyzed the immunological profiles and conducted RNA sequencing (RNAseq) on peripheral blood samples from four patients. Results A total of twenty-six patients were enrolled, with twenty-one completing the study. Both DM and ASS patients demonstrated significant improvements in disease activity. Among these, the percentage of Tfh cells in peripheral blood decreased by 81.0% (17/21) of patients (p = 0.003). Significant reductions in Th17 cells were observed in vivo in the PBMCs of these patients (p = 0.017). In vitro, Tfh cells (2.88 ± 1.13 vs 2.28 ± 0.92, p < 0.001), Th17 cells (1.42 ± 0.92 vs 1.01 ± 0.74, p = 0.016), Treg cells (2.06 ± 1.26 vs 0.98 ± 0.65, p = 0.019) and Tfh17 cells (33.38 ± 15.14 vs 30.28 ± 4.89, p = 0.014) were inhibited. RNAseq analysis revealed significant downregulation of genes associated with the ‘herpes simplex virus 1 infection’ and ‘IL-17 signalling’ pathway. MDAAT scores improved in 21 out of 24 patients. Fifteen (62.5%) patients met the criteria for IMACS DOI. Importantly, no severe adverse events necessitated treatment discontinuation. Conclusion Tofacitinib demonstrated significant immunologic and clinical effectiveness in DM and ASS patients, reducing key immune cell populations and downregulating immune activation pathways.