Predictors of Treatment Failure with JAK Inhibitors in Alopecia Areata: T-Cell Dynamics and Clinical Determinants of Inadequate Response

The Janus kinase (JAK) inhibitors have been the first targeted treatments to be approved for Alopecia areata (AA), an autoimmune disease that affects T cells and results in non-scarring hair loss. Although baricitinib (2022), ritlecitinib (2023), and deuruxolitinib (2024) have been recently approved, there is still an important percentage of patients not achieving enough or any response (30-55% depending on the agent and endpoint). This review analyses in detail immunological and clinical factors that are involved in treatment failure in AA with JAK inhibitors, with a special emphasis on the dynamics of T cells, Treg dysfunction, Th2 skewing, AA phenotype and baseline disease burden. Mechanistic studies, real-world cohorts and phase 3 studies all support a multifactorial model of non-response, in which disease duration, alopecia totalis/alopecia universalis subtype, baseline atopy, high baseline Severity of Alopecia Tool (SALT) scores >75, and low Treg compartment size are all independent risk factors for failure. Single-cell transcriptomic evidence of emerging data indicates hyperactivation of CD8⁺ effector memory T cells and JAK-STAT pathway redundancy as cellular substrates of resistance. The need for clinical translation to a biomarker-stratification framework is pressing. This review summarises the existing data and suggests further research in personalised JAK inhibitor treatment of AA.