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

Xiaoyan Xing1,2, Qinghong Liu1,2, Naidi Wang1,2

  • 1Department of Rheumatology and Immunology and Beijing Key Laboratory for Rheumatism and Immune Diagnosis (BZ0135), Peking University People's Hospital, Beijing, China.

Rheumatology (Oxford, England)
|January 28, 2025
PubMed
Abstract

Insights

Tofacitinib effectively treated dermatomyositis and anti-synthetase syndrome by reducing key immune cells like T follicular helper cells. This treatment showed significant clinical improvements and was well-tolerated, offering a new option for patients.

Area of Science:

  • Immunology
  • Rheumatology
  • Pharmacology

Background:

  • Dermatomyositis (DM) and anti-synthetase syndrome (ASS) are autoimmune conditions characterized by inflammation and immune system dysregulation.
  • Conventional treatments for DM and ASS often have limited efficacy or significant side effects.
  • Targeting specific immune pathways, such as those involving T cells, may offer a more effective therapeutic approach.

Purpose of the Study:

  • To evaluate the efficacy and safety of tofacitinib in patients with active DM and ASS who had an inadequate response to standard therapies.
  • To assess the impact of tofacitinib on key immune cell populations, including T follicular helper (Tfh) cells and Th17 cells.
  • To investigate the molecular mechanisms underlying tofacitinib's therapeutic effects through RNA sequencing.

Main Methods:

  • A clinical trial involving 26 patients with active DM or ASS who received tofacitinib 5 mg twice daily.
  • Primary endpoint: reduction in peripheral blood Tfh cells at week 24.
  • Secondary endpoints: clinical disease activity scores, immunological profiling, and RNA sequencing of peripheral blood mononuclear cells (PBMCs).

Main Results:

  • Significant reduction in Tfh cells (81% of patients) and Th17 cells in peripheral blood.
  • In vitro studies showed inhibition of Tfh, Th17, Treg, and Tfh17 cells.
  • Clinical improvements observed, with enhanced Myositis Disease Activity Assessment Tool (MDAAT) scores and achievement of the International Myositis Assessment and Clinical Studies (IMACS) definition of improvement (DOI) in a majority of patients.
  • RNA sequencing revealed downregulation of genes related to 'herpes simplex virus 1 infection' and 'IL-17 signalling' pathways.
  • Tofacitinib was well-tolerated, with no severe adverse events requiring treatment discontinuation.

Conclusions:

  • Tofacitinib demonstrated significant immunologic and clinical effectiveness in treating active DM and ASS.
  • The drug effectively reduced specific pathogenic immune cell populations and modulated immune activation pathways.
  • Tofacitinib represents a promising therapeutic option for patients with DM and ASS refractory to conventional treatments.
Keywords:
anti-synthetase syndromeclinical responsedermatomyositisimmune cell subsetstofacitinib

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