Ritlecitinib, a JAK3 /TEC inhibitor, modulates the markers of celiac autoimmunity in alopecia areata and vitiligo patients

Arch Dermatol Res. 2025 Jan 18;317(1):280. doi: 10.1007/s00403-024-03784-6.

Abstract

Background: Celiac disease (CeD) has shown an association with autoimmune disorders including vitiligo and alopecia areata (AA). Ritlecitinib, a JAK3 and TEC kinase family inhibitor, has been approved for treatment of patients with AA and is in late-stage development for vitiligo. Ritlecitinib inhibits cytotoxic T cells, NK cells, and B cells which play a role in the pathogenesis of CeD.

Objective: We aimed to explore the potential effect of ritlecitinib on CeD serology levels before and after ritlecitinib treatment in research participants of clinical trials.

Methods: The effect of ritlecitinib on CeD serology (tTG-IgA, DGP-IgA/IgG) levels was retrospectively evaluated in participants from three phase 2 and one phase 3 ritlecitinib clinical trials including participants with active AA, rheumatoid arthritis (RA) and vitiligo, whose serum samples at baseline and post-treatment were available. All statistical comparisons of the changes between initial and follow-up samples used the Wilcoxon matched pairs exact test.

Results: Of 1146 research participants, 21 individuals had a positive tTG-IgA in their baseline samples (positivity rate, 0.018, 95% CI = 0.011-0.028). Among these 21 individuals, follow-up samples were available in 15 participants from the ritlecitinib group and in 3 from the placebo group. In follow-up samples, the values of tTG-IgA in the 15 participants treated with ritlecitinib significantly decreased from baseline (p < 0.01), while in the placebo group the tTGA-IgA levels remained close to the baseline values.

Conclusion: A decrease in CeD serology levels with ritlecitinib treatment suggests that ritlecitinib may provide beneficial effect in CeD.

Keywords: Alopecia areata; Celiac autoimmunity; Ritlecitinib; Vitiligo.

MeSH terms

  • Adult
  • Aged
  • Alopecia Areata* / blood
  • Alopecia Areata* / drug therapy
  • Alopecia Areata* / immunology
  • Autoimmunity / drug effects
  • Biomarkers / blood
  • Celiac Disease* / drug therapy
  • Celiac Disease* / immunology
  • Female
  • Humans
  • Janus Kinase 3* / antagonists & inhibitors
  • Male
  • Middle Aged
  • Piperidines / therapeutic use
  • Protein Kinase Inhibitors / therapeutic use
  • Pyrimidines
  • Pyrroles
  • Retrospective Studies
  • Vitiligo* / drug therapy
  • Vitiligo* / immunology
  • Young Adult

Substances

  • Janus Kinase 3
  • Protein Kinase Inhibitors
  • JAK3 protein, human
  • PF-06651600
  • Biomarkers
  • Piperidines
  • Pyrimidines
  • Pyrroles