Dupilumab and Psoriasis Risk in Patients With Atopic Dermatitis: A Multicenter Cohort Study

Dupilumab treatment for atopic dermatitis (AD) has been linked to incident psoriasis, possibly reflecting a T helper 2 (Th2) to Th17 immune shift, but its risk relative to alternative contemporary AD-directed therapies is unclear. To address this question, we performed parallel retrospective cohort studies using the TriNetX Global Collaborative Network and Epic Cosmos. In TriNetX, propensity score-matched dupilumab cohorts were compared with topical corticosteroids (TCS), alternative anti-Th2 biologics (nemolizumab, lebrikizumab, tralokinumab) or Janus kinase (JAK) inhibitors (abrocitinib, upadacitinib), with two-year incident psoriasis assessed via Cox hazard ratios (HRs). Cosmos' larger patient pool permitted an exploratory analysis with agent-level comparisons, evaluating relative risk (RR) of incident psoriasis within a 17-month span. Dupilumab was not associated with increased two-year psoriasis risk versus TCS (HR 0.91, 95% CI 0.77-1.08), alternative anti-Th2 biologics (HR 1.03, 0.49-2.14) or JAK inhibitors (HR 0.86, 0.48-1.51). The data from Cosmos were in line with these findings, with equivalent or lower incidence with dupilumab relative to alternative agents. These data do not support a dupilumab-specific risk of incident psoriasis and may instead reflect diagnostic ambiguity and/or genetic susceptibility to systemic immune shifts; nevertheless, these proposed explanations require confirmation in prospective studies incorporating clinical, histopathologic and genetic data.