Efficacy and Safety of Targeted Systemic Therapies in Head and Neck Atopic Dermatitis: A Systematic Review and Meta‐Analysis

Background A distinctive and difficult phenotype, head and neck atopic dermatitis (AD) is linked to a higher disease burden and inconsistent treatment response. The effectiveness of targeted systemic therapy in this field is currently little understood. Objectives To evaluate both the safety and effectiveness of targeted systemic therapies for individuals’ AD affecting the head and neck, such as tralokinumab, dupilumab, and upadacitinib. Methods A meta‐analysis and systematic review were conducted using PRISMA guidelines. In three databases (PubMed, Web of Science, and EMBASE), we searched for relevant research. The qualifying research included observational studies and randomized controlled trials that reported outcomes among patients with head and neck involvement. The primary findings included the head and neck Eczema Area and Severity Index (H&N EASI‐75) and the percentage change in EASI. The Numerical Rating Scale for pruritus, the Dermatology Life Quality Index for quality of life, and safety outcomes were secondary results. The meta‐analysis was conducted using a random‐effects model. Results Twelve studies were included. The pooled H&N EASI‐75 response rate was 51% (95% CI: 40–62), with a mean percentage reduction in EASI of −72.86% (95% CI: −78.98 to −66.74). Significant improvements were observed in pruritus (mean change −4.38) and quality of life (−9.97). Across indirect, between‐study subgroup comparisons, studies of upadacitinib showed numerically greater effect estimates than studies of dupilumab or tralokinumab; in the absence of head‐to‐head trials, these comparisons are hypothesis‐generating rather than definitive. The overall prevalence of adverse events was 48%, with conjunctivitis (7%) and herpes zoster (2%) reported. Substantial heterogeneity was noted. Conclusions Targeted systemic therapies were associated with clinically meaningful improvements in head and neck AD, although substantial heterogeneity and the indirect nature of the drug‐specific comparisons warrant cautious interpretation. Differences in efficacy and safety profiles across agents highlight the importance of individualized treatment selection, and further head‐to‐head comparative studies are warranted.