Systemic risk profiles of topical ruxolitinib and oral Janus kinase inhibitors in patients with atopic dermatitis: A retrospective cohort study from the TriNetX network

Background Topical ruxolitinib is a Janus-activated kinase (JAK) inhibitor used to treat atopic dermatitis. The U.S. Food and Drug Administration issued a boxed warning for topical ruxolitinib, assuming it carries similar risks to oral JAK inhibitors. Objective To compare the incidence of adverse events in patients with atopic dermatitis treated with topical ruxolitinib, oral JAK inhibitors, or conventional topical therapies (corticosteroids and calcineurin inhibitors). Methods We conducted a retrospective cohort study using TriNetX. Patients treated with topical ruxolitinib, oral JAK inhibitors, or conventional topical therapies were included. Propensity score matching accounted for demographics and thromboembolic risk factors. Adverse events were compared using t tests with Benjamini-Hochberg correction. Results Topical ruxolitinib users had significantly lower incidences of arterial thrombosis and tuberculosis compared to oral JAK inhibitor users. Compared to controls, topical ruxolitinib users had decreased risk of all-cause mortality, cerebrovascular accidents, and venous thromboembolism. Oral JAK inhibitor users had a higher incidence of herpes zoster compared to controls. Notably, there were low rates of adverse events across all groups. Limitations The study lacks survival analysis and had longer follow-up in control groups, which may influence event detection. Conclusion Topical ruxolitinib demonstrates a favorable systemic safety profile and may warrant reconsideration of its boxed warning.