Ritlecitinib and brepocitinib demonstrate significant improvement in scalp alopecia areata biomarkers

Emma Guttman-Yassky, Ana B. Pavel, Aisleen Diaz, Ning Zhang, Ester Del Duca, Yeriel Estrada, Brett King, Anindita Banerjee, Christopher Banfield, Lori Ann Cox, Martin E. Dowty, Karen Page, Michael S. Vincent, Weidong Zhang, Linda Zhu, Elena Peeva

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Background: Janus kinase (JAK) inhibitors have shown encouraging results in the treatment of alopecia areata (AA), an autoimmune form of hair loss, in small, uncontrolled studies and case reports. Objective: We conducted a biopsy substudy during the randomized, double-blind, placebo-controlled first 24 weeks of a phase 2a clinical trial that evaluated the efficacy and safety of ritlecitinib, an inhibitor of JAK3 and the tyrosine kinase expressed in hepatocellular carcinoma (TEC) kinase family, and brepocitinib, an inhibitor of tyrosine kinase 2 (TYK2)/JAK1 in the treatment of AA. Methods: Change in biomarkers in lesional scalp biopsy samples between baseline and weeks 12 and 24 was an exploratory end point, and 46 patients participated from the ritlecitinib (n = 18), brepocitinib (n = 16), and placebo (n = 12) groups. Correlations of biomarkers with hair regrowth, measured using the Severity of Alopecia Tool (SALT) score, were also evaluated. Clinical Trial Registration: NCT02974868. Results: At week 24, both ritlecitinib and brepocitinib demonstrated improvement exceeding 100% in the lesional scalp transcriptome toward a nonlesional profile. At week 12, the improvements in scalp tissue were greater with brepocitinib than ritlecitinib; however, at week 24, the improvements were greater with ritlecitinib. Conclusions: For both ritlecitinib and brepocitinib, improvement in the SALT scores was positively associated with expression of TH1 markers and negatively associated with expression of hair keratins. Larger, long-term clinical trials are warranted.

Original languageEnglish
Pages (from-to)1318-1328
Number of pages11
JournalJournal of Allergy and Clinical Immunology
Issue number4
StatePublished - Apr 2022


  • Alopecia areata
  • JAK
  • Janus kinase inhibitors
  • biomarkers
  • cytokines
  • inflammation
  • scalp
  • tyrosine kinase


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