Biologics in alopecia areata: promise, paradox, and the precision medicine frontier

Alopecia areata (AA) is a chronic, immune-mediated non-scarring hair loss affecting approximately 2% of the population. The approval of oral JAK inhibitors has established targeted systemic therapy for moderate-to-severe AA. Incomplete response rates, relapse upon treatment discontinuation, and safety contraindications, however, leave a substantial proportion of patients requiring alternative options.

This review evaluates the immunopathogenic rationale and available clinical evidence for biologic therapies in AA, including inhibitors of tumor necrosis factor (TNF), interleukin-4 receptor α subunit (IL-4 Rα), IL-17, and IL-23. Relevant literature was identified through PubMed and ClinicalTrials.gov (last search: 17 October 2026).

No biologic has demonstrated efficacy in an adequately powered randomized controlled trial in AA. A phase 2a randomized trial of dupilumab showed modest efficacy, most pronounced in patients with elevated baseline IgE. Paradoxically, TNF, IL-17, and IL-23 inhibitors have been implicated in drug-induced AA, a hypothesis-generating observation that warrants cautious interpretation. Given the higher bar set by JAK inhibitors and the risk of paradoxical disease, currently available cytokine-targeting biologics cannot be recommended for AA outside of clinical trials. Endotype-stratified investigation represents the most promising path toward precision immunotherapy in AA.