Ritlecitinib, a JAK3/TEC family kinase inhibitor, stabilizes active lesions and repigments stable lesions in vitiligo

Arch Dermatol Res. 2024 Jul 18;316(7):478. doi: 10.1007/s00403-024-03182-y.

Abstract

The efficacy of ritlecitinib, an oral JAK3/TEC family kinase inhibitor, on active and stable lesions was evaluated in patients with active non-segmental vitiligo in a phase 2b trial (NCT03715829). Patients were randomized to placebo or daily ritlecitinib 50 mg (with or without 4-week 100-mg or 200-mg loading dose), 30 mg, or 10 mg for 24 weeks. Active lesions showed greater baseline expression of inflammatory/immune markers IFNG and CCL5, levels of CD103, and T-cell infiltrates than stable lesions. Patients with more active than stable vitiligo lesions showed higher baseline serum levels of CXCL9 and PD-L1, while patients with more stable than active lesions showed higher baseline serum levels of HO-1. At Week 24, ritlecitinib 50 mg significantly stabilized mean percent change from baseline in depigmentation extent in both active lesions and stable lesions vs. placebo-response, with stable lesions showing greater repigmentation. After 24 weeks of treatment, ritlecitinib 50 mg increased expression of melanocyte markers in stable lesions, while Th1/Th2-related and co-stimulatory molecules decreased significantly in both stable and active lesions. Serum from patients with more active than stable lesions showed decreased levels of ICOS and NK cell activation markers. These data, confirmed at transcription/protein levels, indicate that stable lesion repigmentation occurs early with ritlecitinib, while active lesions require stabilization of inflammation first. ClinicalTrials.gov: NCT03715829.

Keywords: Biomarkers; JAK inhibitor; Non-segmental vitiligo; Ritlecitinib; Vitiligo.

Publication types

  • Randomized Controlled Trial
  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Administration, Oral
  • Adult
  • B7-H1 Antigen / antagonists & inhibitors
  • B7-H1 Antigen / blood
  • B7-H1 Antigen / metabolism
  • Chemokine CCL5 / blood
  • Chemokine CXCL9 / blood
  • Double-Blind Method
  • Female
  • Humans
  • Interferon-gamma
  • Janus Kinase 3* / antagonists & inhibitors
  • Male
  • Melanocytes / drug effects
  • Middle Aged
  • Protein Kinase Inhibitors* / administration & dosage
  • Protein Kinase Inhibitors* / therapeutic use
  • Skin Pigmentation / drug effects
  • Treatment Outcome
  • Vitiligo* / diagnosis
  • Vitiligo* / drug therapy
  • Vitiligo* / immunology
  • Young Adult

Substances

  • Janus Kinase 3
  • Protein Kinase Inhibitors
  • CXCL9 protein, human
  • JAK3 protein, human
  • Chemokine CXCL9
  • CCL5 protein, human
  • Chemokine CCL5
  • IFNG protein, human
  • B7-H1 Antigen
  • Interferon-gamma

Associated data

  • ClinicalTrials.gov/NCT03715829