<![CDATA[Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with skin barrier dysfunction and immune dysregulation. In moderate-to-severe cases, systemic therapy is often required. Dupilumab has been widely used as a biologic therapy targeting the IL-4 and IL-13 pathways, whereas Janus kinase inhibitors (JAK inhibitors, JAKi) exert broader effects through inhibition of the JAK–STAT signaling pathway. This systematic review aimed to evaluate the efficacy and safety profile of JAK inhibitors compared with dupilumab in patients with moderate-to-severe AD. A systematic literature search was conducted using PubMed, ScienceDirect, and the Cochrane Library in accordance with the PRISMA guidelines. English-language articles published between 2020 and 2026 were independently screened by two authors. Eligible studies included adult and/or adolescent patients with moderate-to-severe atopic dermatitis and evaluated oral Janus kinase inhibitors (JAK inhibitors) and/or compared them with dupilumab. The primary outcome was the achievement of EASI-75, while secondary outcomes included the safety profile of the therapies. Eight studies met the inclusion criteria. JAK inhibitors, particularly upadacitinib and abrocitinib, demonstrated rapid clinical improvement, especially in pruritus reduction and achievement of EASI-75 responses. However, JAK inhibitors were more frequently associated with infections, herpes zoster, eczema herpeticum, acne, nausea, and laboratory abnormalities. In contrast, dupilumab was more commonly associated with conjunctivitis, keratitis, and injection-site reactions. JAK inhibitors demonstrated a faster onset of symptom improvement in several studies, particularly with respect to pruritus relief and early EASI responses. Nevertheless, their use should be carefully balanced against the risks of infections, herpes zoster, acne, and laboratory parameter abnormalities. Dupilumab remains an important biologic treatment option with a relatively stable safety profile, although ocular adverse events, such as conjunctivitis and keratitis, should be anticipated.]]>
