Tofacitinib treatment for active dermatomyositis and anti-synthetase syndrome: a prospective cohort pilot study.

Abstract

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). 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 in T follicular helper (Tfh) cells at week 24. Key secondary end points included clinical scores. Moreover, we analysed the immunological profiles and conducted RNA sequencing (RNAseq) on peripheral blood samples from four patients. A total of 26 patients were enrolled, with 21 completing the study. Both DM and ASS patients demonstrated significant improvements in disease activity. Among these patients, the percentage of Tfh cells in peripheral blood decreased in 81.0% (17/21) of them (P = 0.003). Significant reductions in Th17 cells were observed in vivo in the peripheral blood mononuclear cells (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. Myositis Disease Activity Assessment Tool (MDAAT) scores improved in 21 out of 24 patients. Fifteen (62.5%) patients met the criteria for International Myositis Assessment and Clinical Studies (IMACS) definition of improvement (DOI). Importantly, no severe adverse events necessitated treatment discontinuation. Tofacitinib demonstrated significant immunologic and clinical effectiveness in DM and ASS patients, reducing key immune cell populations and downregulating immune activation pathways.