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

ABSTRACT

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.