Update on the treatment of atopic dermatitis: biologics and small molecules

Purpose: The advent of targeted therapies has revolutionized the treatment landscape of atopic dermatitis (AD), particularly through the introduction of biologics and small-molecule agents. This review summarizes current evidence regarding the efficacy, safety, and clinical applications of biologics such as dupilumab, tralokinumab, lebrikizumab, and nemolizumab, as well as small-molecule inhibitors including Janus kinase (JAK) inhibitors, phosphodiesterase-4 (PDE4) inhibitors, and aryl hydrocarbon receptor (AhR) modulators.Current Concepts: AD is a chronic, relapsing inflammatory skin disorder characterized by a complex interplay between skin barrier dysfunction and immune dysregulation. Biologic therapies have targeted key cytokines involved in AD pathogenesis: dupilumab inhibits interleukin (IL)-4 and IL-13; tralokinumab and lebrikizumab selectively target IL-13; and nemolizumab blocks IL-31. In addition, small-molecule JAK inhibitors such as upadacitinib, baricitinib, and abrocitinib are now used for moderate-to-severe AD. Topical JAK inhibitors (e.g., ruxolitinib, delgocitinib), PDE4 inhibitors, and AhR modulators have also shown promise in clinical trials, offering new therapeutic options. Clinical studies have consistently demonstrated marked improvements in disease severity, pruritus, and quality of life, with generally acceptable safety profiles. Nonetheless, questions remain regarding long-term safety, patient selection, cost-effectiveness, and optimal sequencing of these therapies.Discussion and Conclusion: Targeted biologics and small-molecule therapies have significantly improved quality of life and long-term disease control for patients with AD. Ongoing and future studies are essential to refine personalized treatment approaches based on individual disease phenotypes, biomarkers, and patient-specific factors.