Psoriasis Risk with Dupilumab in Atopic Dermatitis: Clinical Relevance and Caution

A large-scale retrospective cohort study published in JAMA Dermatology has identified a statistically significant but clinically modest association between dupilumab use and an elevated risk of psoriasis among adults with atopic dermatitis (AD). This finding, while noteworthy, prompts a nuanced interpretation regarding its practical implications.

Using the TriNetX Global Collaborative Network, researchers evaluated data from over 214,000 adults diagnosed with AD. The study focused on 9,860 matched patients initiating dupilumab versus a control group prescribed other systemic agents, none of whom had prior exposure to dupilumab. Psoriasis incidence was the primary endpoint, analyzed via Kaplan-Meier survival curves and Cox proportional hazards models.

Key outcomes included:

• Cumulative psoriasis incidence: 2.86% in the dupilumab cohort versus 1.79% in controls.
• Hazard ratio (HR): 1.58 (95% CI, 1.25–1.99), indicating a 58% increased relative risk.
• Number needed to harm (NNH): 94, suggesting that for every 94 patients treated with dupilumab, one additional case of psoriasis may be attributable to the drug.

The increased risk held consistent across several subgroups:

• Patients without atopic comorbidities (HR, 1.42).
• Those with low baseline IgE levels (HR, 1.59).

A validation cohort of asthma patients—without comorbid AD—showed an even higher relative risk (HR, 2.13), underscoring the potential drug-specific rather than disease-specific nature of this association. However, the risk of developing psoriatic arthritis did not reach statistical significance.

Despite the robust dataset and the statistically significant hazard ratios, the clinical relevance of these findings remains modest. The NNH of 94 indicates that while the association is real, the absolute risk to individual patients is low. This is a critical point for clinicians considering dupilumab, especially given its well-established efficacy in managing moderate to severe AD.The authors emphasized that this potential risk should not deter use but rather inform shared decision-making. Clinicians are encouraged to monitor for new-onset psoriatic changes, particularly in patients with suggestive symptoms or personal/family history of psoriasis.

Mechanistically, the paradoxical induction of psoriasis by dupilumab—an IL-4/IL-13 pathway inhibitor—may involve a cytokine imbalance, possibly tipping immune response toward a Th1/Th17-dominant profile. While this hypothesis aligns with previous case reports, causality remains speculative.Further prospective studies, ideally with mechanistic endpoints, are needed to clarify:

• Whether dupilumab directly induces psoriasis or unmasks latent disease.
• Biomarkers predictive of susceptibility.
• Differential risk across demographic or genetic profiles.

While dupilumab remains a frontline therapy for AD, this new data adds a layer of complexity to patient management. Awareness of the potential for psoriasis—albeit uncommon—may guide clinicians in vigilant monitoring and timely dermatologic consultation, enhancing patient outcomes without undermining the therapeutic benefits of biologic therapy.