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

Introduction 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.Areas covered 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).Expert opinion 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.