Novel Therapeutic Strategies for Atopic Dermatitis: Biomarker Modulation and Clinical Implications. A Systematic Review

Advances in the understanding of atopic dermatitis (AD) pathogenesis have driven the development of innovative systemic therapies targeting key immunologic pathways. This systematic review summarizes current evidence on the impact of biologic agents, Janus kinase (JAK) inhibitors, and other emerging treatments on AD-related biomarkers and their correlation with clinical outcomes. A comprehensive literature search was conducted across PubMed, Embase, Scopus, and Web of Science for studies published between 2014 and 2024. Eighty studies met the inclusion criteria. Dupilumab was the most extensively investigated therapy, followed by tralokinumab, JAK inhibitors, and novel agents such as amlitelimab, stapokibart, and tezepelumab. Across drug classes, consistent reductions in CCL17/TARC, LDH, and total IgE levels were observed, generally paralleling clinical improvement in EASI and SCORAD scores. Transcriptomic and proteomic analyses revealed normalization of Th2/Th22 inflammatory signatures and restoration of barrier-related gene expression, while microbiome studies showed a reduction in Staphylococcus aureus colonization. Despite these advances, the heterogeneity of study designs and analytical techniques limits the comparability of results. CCL17 and LDH currently represent the most reliable biomarkers associated with disease severity and treatment response, although their limited specificity restricts clinical applicability. Future research should aim to validate integrated biomarker panels combining immunologic, transcriptomic, and microbiomic data to enable precision medicine approaches in atopic dermatitis management.