A comprehensive analysis of nearly 20,000 patients with atopic dermatitis has revealed that treatment with dupilumab may increase the risk of developing psoriasis, according to new research published in JAMA Dermatology. The study found a 58% higher risk of psoriasis development among patients treated with dupilumab compared to those receiving other systemic therapies.
Study Design and Population
The retrospective cohort study utilized data from the TriNetX Global Collaborative Network, analyzing 19,720 patients matched 1:1 by age, sex, race, comorbidities, laboratory measurements, and prior medications. The study population comprised 9,860 patients receiving dupilumab and 9,860 patients receiving other systemic medications including corticosteroids, methotrexate, cyclosporine, azathioprine, or mycophenolate mofetil.
The study population was predominantly female (55.2%) with a mean age of 44.8 years. White individuals accounted for 50.2% of patients, followed by African American or Black individuals (18.2%) and Asian individuals (10.2%). The most common comorbidities across both groups were asthma, allergic rhinitis, and hypertension.
Key Findings
Over a 3-year follow-up period, the cumulative incidence of psoriasis was significantly higher in the dupilumab group at 2.86% compared to 1.79% in the control group (P < .001). This translated to a hazard ratio of 1.58 (95% CI, 1.25-1.99), representing a 58% increased risk of developing psoriasis.
The researchers calculated a number needed to harm (NNH) of 94, meaning that for every 94 patients treated with dupilumab, one additional case of psoriasis could be expected compared to other systemic therapies. The absolute risk difference over three years was 1.07 percentage points.
Risk Across Subgroups
The elevated psoriasis risk persisted across multiple patient subgroups, including:
- Patients older than 60 years (HR, 1.77; 95% CI, 1.22-2.58)
- Male patients (HR, 1.55; 95% CI, 1.08-2.22)
- Female patients (HR, 1.63; 95% CI, 1.19-2.24)
- White patients (HR, 1.43; 95% CI, 1.05-1.93)
- Patients with atopic comorbidities (HR, 1.56; 95% CI, 1.11-2.19)
- Patients without atopic comorbidities (HR, 1.42; 95% CI, 1.06-1.89)
Notably, the risk remained elevated even in patients who never had blood IgE levels above 0.048 mg/dL (HR, 1.59; 95% CI, 1.03-2.01).
Validation in Asthma Patients
To further validate their findings, researchers examined patients with asthma who did not have atopic dermatitis. This analysis confirmed a similar association, showing a 113% greater risk of psoriasis development (HR, 2.13; 95% CI, 1.38-3.31) in dupilumab-treated patients.
Immunological Mechanisms
The study authors suggest that immune shifts caused by dupilumab could trigger psoriasis, particularly in individuals with an immune profile that includes inflammation primarily driven by Th17 cells. Atopic dermatitis is considered an autoimmune disease, and Th17 cells play key roles in both immunity and inflammation by releasing interleukin-17, a known mediator of inflammation in autoimmune diseases.
Clinical Implications
Despite the observed association, the researchers emphasized that the absolute increased risk remains small and should be carefully weighed against dupilumab's well-established benefits in controlling moderate to severe atopic dermatitis. The findings underscore the importance of clinical monitoring for psoriasis development in patients with atopic dermatitis receiving dupilumab.
The study authors noted that their 58% higher 3-year risk finding echoed a 2022 report from the World Health Organization, which showed a link between dupilumab and higher risk of psoriasis at 48%. They concluded that despite the increased relative risk, the estimated NNH of 94 reflects the limited clinical relevance of the absolute risk, which should be weighed against dupilumab's proven efficacy in treating atopic dermatitis.
