Biologic and Small Molecule Therapy for Treating Moderate to Severe Atopic Dermatitis: Mechanistic Considerations

Atopic dermatitis (AD) is a complex and heterogeneous skin disease where achieving complete clinical clearance for most patients has proven challenging through single cytokine inhibition. Current studies integrate biomarkers and evaluate their role in AD, aiming to advance our understanding of the diverse molecular profiles implicated. While traditionally characterized as a Th2-driven disease, extensive research has recently revealed the involvement of Th1, Th17, and Th22 immune pathways, as well as the interplay of pivotal immune molecules, such as OX40, OX40 ligand (OX40L), thymic stromal lymphopoietin (TSLP), and IL-33. This review will explore the mechanistic effect of treatments for AD, focusing on monoclonal antibodies and JAK inhibitors. It will describe how these treatments modulate immune pathways, and examine their impact on key inflammatory and barrier biomarkers.