Use of oral Janus kinase inhibitors for the treatment of severe alopecia areata: narrative review and real-world experience

Alopecia areata (AA) is a common autoimmune, non-scarring hair loss disease in which anagen hair follicles are predominantly affected. Typically, from a single to multiple and round to oval patchy hair loss is observed in AA with a tendency for spontaneous regression; however, total scalp or whole-body hair loss can be seen in severe cases. 'IFN-γ-IL-15 cytokine loop' existing between autoreactive cytotoxic T cells and hair follicle epithelial cells underlies AA intractability, leading to the development of Janus kinase inhibitors (JAKis) inhibiting the downstream signaling pathways as remedies for severe AA. JAKis were shown to be effective and tolerable in clinical studies and now, baricitinib and ritlecitinib have been used for severe AA in Japan. Despite the fact that these medications can achieve clinically meaningful hair regrowth in around 30%-40% of treated patients, nearly 30% of patients have been found to be non-responders both in post-hoc analyses and real-world experience including ours. In addition, relapse can be seen not only in those who are downtitrated or discontinued medication but also in patients under treatment, leaving room for further improvement/development. New medications and/or dosing regimens tested in currently ongoing/planned clinical trials have potential to address JAKi-associated unmet needs in severe AA.