Question：
Is dupilumab treatment associated with increased psoriasis risk in patients with atopic dermatitis？
Findings：
In this cohort study of 19720 patients with atopic dermatitis, those who received dupilumab (n = 9860) experienced a 58% higher risk of developing psoriasis compared with matched patients with atopic dermatitis who were receiving other systemic agents, with a number needed to harm of 94.
Meaning：
The study results suggest that dupilumab use in atopic dermatitis was associated with increased psoriasis risk, suggesting that T helpler 2 antagonism may skew the immune response toward T helper 17.
Importance：
Patients with atopic dermatitis (AD) have been reported to develop psoriasis during dupilumab treatment. Whether this represents a true association or an incidental event remains unclear.
Objective：
To compare psoriasis risk in patients with AD who are prescribed dupilumab vs other systemic agents.
Design, Setting, and Participants：
This population-based retrospective cohort study with 3-year follow-up, with analyses completed on October 19, 2024, included 214 430 adult patients with AD from the TriNetX Global Collaborative Network. Individuals newly prescribed dupilumab (dupilumab cohort) and those newly prescribed the other systemic agents without dupilumab exposure (control cohort) were included. Propensity score matching at a 1:1 ratio based on age, sex, race, comorbidities, laboratory measurements, and prior medications was conducted.
Exposures：
Dupilumab vs the other systemic agents (corticosteroids, methotrexate, cyclosporine, azathioprine, or mycophenolate mofetil).
Main Outcomes and Measures：
The primary outcome was incident psoriasis. Cumulative incidence was assessed using Kaplan-Meier plots and risks via Cox regression.
Results：
After matching, each cohort comprised 9860 patients, with 10 891 female individuals (55.2%), a mean (SD) age of 44.8 (20.3) years, 3582 African American or Black individuals (18.2%), 2004 Asian individuals (10.2%), and 9901 White individuals (50.2%). The 3-year cumulative psoriasis incidence was higher in the dupilumab cohort than the control cohort (2.86% vs 1.79%; P < .001). The number needed to harm for psoriasis was 94 for dupilumab vs the other systemic agents. The dupilumab cohort showed an increased risk for psoriasis (hazard ratio [HR], 1.58; 95% CI, 1.25-1.99), although the risk for psoriatic arthritis was not significant (HR, 1.97; 95% CI, 0.75-5.18). This increased risk was also observed in various AD subgroups, including those without atopic comorbidities (HR, 1.42; 95% CI, 1.06-1.89) or with pretreatment immunoglobulin E levels less than 0.048 mg/dL (to convert to mg/L, multiply by 10; HR, 1.59; 95% CI, 1.26-2.01). The association between dupilumab and psoriasis was further supported by validation in patients with asthma without AD (HR, 2.13; 95% CI, 1.38-3.31).
Conclusions and Relevance：
The results of this cohort study suggest that patients with AD who were prescribed dupilumab exhibited a higher relative risk of developing psoriasis compared with those receiving other systemic agents. Given an estimated number needed to harm of 94, the absolute risk may have limited clinical relevance and should be weighed against dupilumab’s established efficacy in treating AD.
