Apremilast and Tofacitinib Exert Differential Effects in the Humanized Mouse Model of Alopecia Areata

The study compared the therapeutic effects of apremilast, a PDE4 inhibitor, and tofacitinib, a JAK inhibitor, in a humanized mouse model of alopecia areata (AA). Scalp skin xenotransplants from three healthy male volunteers were grafted onto mice, which were then divided into three groups for treatment with methylcellulose (vehicle), apremilast, or tofacitinib. The clinical efficacy was analyzed, and histology and immunohistochemistry were performed to assess the treatments' effects. The results showed that tofacitinib-treated mice had a higher response rate (53%) and mean hair number per responder graft (4.6) compared to apremilast (25% response rate, 1.9 mean hair number) and vehicle (8% response rate, 1.2 mean hair number). Apremilast did not significantly restore hair follicle immune privilege, reduce hair follicle dystrophy, or decrease perifollicular CD8+ T-cell infiltrates. In contrast, tofacitinib had a strong therapeutic effect. The study concluded that the humanized mouse model of AA is suitable for pre-clinical drug screening and that tofacitinib is a promising pharmacological intervention for AA management, despite potential long-term risks associated with systemic use.