Targeting inflammation: the emerging role of JAK inhibitors in dermatologic and rheumatologic pharmacotherapy

Background Janus kinase (JAK) inhibitors have changed the treatment of immune-mediated dermatologic and rheumatologic disease by targeting intracellular cytokine signaling. The ORAL Surveillance trial and the regulatory actions that followed made safety a primary determinant of clinical positioning. Interpretation depends on separating what has been shown for a given molecule in a given population from what has been extrapolated across a heterogeneous class. Methods We performed a narrative review of PubMed and MEDLINE through 31 July 2026, supplemented by reference lists and by United States Food and Drug Administration (FDA) and European Medicines Agency (EMA) documents. Available studies were eligible if they informed the pharmacology, efficacy, safety, or regulatory status of JAK-pathway inhibitors. Evidentiary weight was assigned hierarchically by study design. Results Efficacy is established in rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, juvenile idiopathic arthritis, giant cell arteritis, atopic dermatitis, alopecia areata, plaque psoriasis, vitiligo, and chronic hand eczema. Filgotinib, a JAK1-preferential inhibitor authorized in Europe and Japan but not the United States, is reviewed alongside FDA-approved agents. ORAL Surveillance found higher rates of major adverse cardiovascular events (3.4% versus 2.5%) and malignancy (4.2% versus 2.9%) with tofacitinib than with tumor necrosis factor inhibitors among patients with rheumatoid arthritis aged 50 years or older with at least one cardiovascular risk factor. Regulators then extended warnings across systemic agents, whereas direct evidence for other molecules, routes, and indications remains uneven. Selectivity has not been shown to confer safety superiority. Conclusion These agents are pharmacologically diverse rather than uniform. Selection should follow indication, treatment history, route, and baseline cardiovascular, malignancy, thromboembolic, infectious, and reproductive risk, with structured screening and monitoring. Long-term comparative safety data remain incomplete.