The Use of JAK Inhibitors in AD Affecting Difficult-to-Treat Areas: Lessons from Real-Life

Background: Difficult-to-treat anatomical areas in atopic dermatitis (AD), including the head and neck, hands, genital and intertriginous regions, are frequently associated with therapeutic refractoriness, persistent pruritus, and substantial functional and psychosocial burden. Real-world evidence (RWE) regarding the effectiveness of Janus kinase (JAK) inhibitors in these site-dominant phenotypes remains fragmented. This structured narrative review aimed to synthesize available RWE on abrocitinib, baricitinib, and upadacitinib in AD involving difficult-to-treat areas. Methods: A comprehensive search of PubMed, Ovid MEDLINE, Scopus, Embase, and the Cochrane Library was conducted up to 31 December 2025. Real-world observational studies reporting site-specific outcomes in patients with AD treated with JAK inhibitors were included. Primary randomized controlled trial efficacy analyses were excluded, while relevant post hoc regional analyses were considered. A total of 22 studies met eligibility criteria for qualitative synthesis. Results: Across heterogeneous real-world cohorts, JAK inhibitors demonstrated clinically meaningful improvement in difficult anatomical regions, particularly the head and neck and hands. Rapid pruritus reduction was a consistent and clinically relevant finding. Safety profiles were broadly aligned with clinical trial data. Conclusions: Real-world data support JAK inhibitors as effective options for anatomically complex AD phenotypes, warranting further standardized regional assessment.