Alopecia Areata Lesions Show Significant Changes In Immune And Keratin Biomarkers That Correlate With Clinical Improvement With Oral Janus Kinase Inhibitors PF-06651600 (JAK3) And PF-06700841 (TYK2/JAK1)

The study demonstrated that oral JAK3 (PF-06651600) and TYK2/JAK1 (PF-06700841) inhibitors were effective and well-tolerated in patients with moderate to severe alopecia areata, showing significant clinical improvements. In a Phase 2 trial involving 46 patients, significant changes in lesional scalp biomarkers were observed after 12 and 24 weeks of treatment. Specifically, there was a notable downregulation of T-cell activation, Th1, Th2, and IL12/23 pathways, and an upregulation of hair keratins, which correlated with clinical improvements measured by the Severity of Alopecia Tool score. These changes were not observed in the placebo group. The study found that patients with a shorter duration of alopecia areata (<3.5 years) experienced greater improvements, highlighting the potential of these inhibitors in treating alopecia areata by modulating immune responses and enhancing hair keratin expression.