JAK Inhibitors for Alopecia Areata: Approved Therapies, Efficacy, and Unanswered Questions.

Alopecia areata (AA) is a common autoimmune disorder characterized by non-scarring hair loss. While traditionally viewed as a T-cell-mediated disease, recent advances have elucidated the central role of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway in its pathogenesis, establishing a self-sustaining inflammatory loop. The identification of this pathway has transformed AA from a condition with limited therapeutic options to one with targeted biological interventions. Over the past five years, multiple JAK inhibitors have received regulatory approval or shown promising results in clinical trials. Baricitinib, a selective JAK1/JAK2 inhibitor, became the first FDA-approved systemic treatment for severe AA, followed by ritlecitinib, which targets JAK3 and TEC family kinases and deuruxolitinib targeting the JAK1/2. Other agents, including ivarmacitinib, and the topical agent delgocitinib, are under active investigation, offering varying selectivity profiles and routes of administration. Compared with conventional therapies, JAK inhibitors such as baricitinib and ritlecitinib demonstrated therapeutic efficacy rates of 40-50% in Phase III clinical trials. Because head-to-head trials among JAK inhibitors in AA remain lacking, the comparative efficacy discussed in this review is derived primarily from indirect, cross-trial comparisons and network meta-analyses. Despite these remarkable advances, the field currently faces several significant challenges, including variable treatment responses, incomplete hair regrowth in patients with severe AA, potential long-term safety risks, and the absence of validated biomarkers to guide patient selection or predict therapeutic outcomes. Comparative efficacy, treatment challenges, and future directions including combination strategies and biomarker-guided therapy are also discussed to support informed clinical decision-making and highlight unmet needs in AA treatment.