JAK inhibitors for the treatment of VEXAS syndrome

Exp Biol Med (Maywood). 2023 May;248(5):394-398. doi: 10.1177/15353702231165030. Epub 2023 May 26.

Abstract

Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a novel described autoinflammatory entity for which the diagnosis is defined by somatic mutations of the UBA1 X-linked gene in hematopoietic progenitor cells. The clinical manifestations are heterogeneous since they range from autoinflammatory symptoms to the presence of underlying hematologic disorders such as myelodysplastic syndromes. Response to treatment in VEXAS is very poor and to date, the therapeutic strategies adopted are only partially effective. However, recently described cohorts of subjects with VEXAS treated with Janus kinase inhibitors (JAK-I) proved that these drugs can be effective in the treatment of several manifestations related to the disease. Herein, we carried out a brief literature review that includes cohorts and single cases in which JAK-I were adopted as a promising strategy to manage VEXAS patients. Subsequently, we described our experience with JAK-I in VEXAS, illustrating the first case, to our knowledge, of a 65-year-old man who was successfully treated with the selective JAK-1 inhibitor filgotinib.

Keywords: JAK inhibitors; VEXAS; autoinflammatory syndrome; chondritis; filgotinib; myelodysplastic syndrome.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Aged
  • Genes, X-Linked
  • Hematopoietic Stem Cells
  • Humans
  • Janus Kinase Inhibitors* / therapeutic use
  • Male
  • Mutation
  • Myelodysplastic Syndromes*

Substances

  • Janus Kinase Inhibitors

Supplementary concepts

  • VEXAS syndrome