TYK2 Inhibition with Deucravacitinib Improves Clinical Outcomes and Resolves Interferon-Driven Inflammation in Lichen Planopilaris

In a clinical trial involving 10 patients with Lichen Planopilaris (LPP), treatment with deucravacitinib, a TYK2 inhibitor, at 6 mg BID for 24 weeks resulted in significant clinical improvements, as evidenced by enhanced PGA (88.9%, p=0.008), LPPAI (-2.3 points, SD 1.1, p=0.002), and Skindex-16 (-21.0 points, SD 22.1, p=0.014) scores. Transcriptomic analyses revealed that untreated LPP was associated with upregulated type I Interferon-stimulated genes and inflammatory pathways, which were downregulated following treatment. Single-cell RNA sequencing showed a reduction in T-cell receptor signaling and antiviral pathways in CD8+GZMK+ T cells, decreased cytokine and interferon signaling in basal keratinocytes, and attenuated CCL19+ fibroblast activity. These findings suggest that deucravacitinib effectively suppresses inflammatory circuits in LPP, offering a promising therapeutic strategy.