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Filgotinib treatment modulates frequency and gene expression of circulating immune cell subsets in ulcerative colitis

Emily R Wendt1, Yan Liang1, Grace Park1

  • 1Gilead Sciences, Inc, Foster City, CA, United States.

Journal of Crohn'S & Colitis
|March 25, 2026
PubMed
Abstract

Insights

Filgotinib treatment for ulcerative colitis (UC) normalized immune cell populations and gene expression in B cells and phagocytic cells. This response was more pronounced in patients who responded well to the Janus kinase (JAK) inhibitor therapy.

Area of Science:

  • Immunology
  • Gastroenterology
  • Pharmacology

Background:

  • Ulcerative colitis (UC) is a chronic inflammatory bowel disease with variable treatment responses.
  • Janus kinase (JAK) inhibitors, like filgotinib, target cytokine signaling pathways involved in inflammation.
  • Understanding filgotinib's effects on peripheral immune cells is crucial for UC treatment optimization.

Purpose of the Study:

  • To investigate the mechanism of action of filgotinib on peripheral immune cells in ulcerative colitis (UC) patients.
  • To characterize changes in immune cell populations and gene expression following filgotinib treatment.
  • To correlate these changes with patient response to therapy.

Main Methods:

  • Peripheral blood mononuclear cells (PBMCs) were collected from UC patients before and after 10 weeks of filgotinib treatment.
  • Flow cytometry and transcriptome sequencing were used to analyze 12 distinct PBMC populations.
  • Data were compared between UC patients (treatment-responsive and non-responsive) and healthy controls.

Main Results:

  • Filgotinib treatment altered the frequency of peripheral B cell populations, particularly memory B cells and plasmablasts, in a treatment-dependent manner.
  • Transcriptomic analysis revealed that filgotinib partially reversed UC-associated gene expression changes in B cells and phagocytic mononuclear cells.
  • These immunomodulatory effects were more significant in patients who showed a positive clinical response to filgotinib.

Conclusions:

  • Filgotinib treatment promotes immune system normalization in UC patients by restoring cellular frequencies and gene expression profiles.
  • The drug's action leads to immune cell profiles in treated UC patients that resemble those of healthy individuals.
  • These findings enhance the understanding of filgotinib's therapeutic mechanism in ulcerative colitis.
Keywords:
basic sciencebiomarkersexperimental modelspathophysiology

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