Topical Ruxolitinib and Delgocitinib Versus Systemic JAK Inhibitors: A Comparative Safety Review

Janus Kinase Inhibitors (JAKi) represent a novel class of drugs for the treatment of chronic inflammatory skin diseases. Topical JAKi (t-JAKi) offer targeted therapy at potentially reduced systemic side effects and improved long-term safety compared to systemic JAKi (s-JAKi). This narrative review assesses the pharmacokinetics and safety profile of currently available t-JAKi, ruxolitinib and delgocitinib, with a comparative analysis to s-JAKi. Pharmacokinetic data show that topical ruxolitinib achieves effective dermal concentrations, with minimal systemic exposure. Clinical trials consistently report low rates of adverse events, primarily application-site reactions, while systemic events such as upper respiratory tract infections occur at rates comparable to placebo. Data on delgocitinib similarly indicate negligible systemic absorption and a favorable safety profile. Taken together, these findings suggest that t-JAKi may represent safer alternatives to s-JAKi for selected patients with localized inflammatory skin diseases, particularly those with comorbidities or heightened systemic risk. Long-term studies and real-world evidence are needed to confirm sustained safety and guide their optimal integration into clinical practice.