Reduced dementia risk in middle-aged and older atopic dermatitis patients treated with dupilumab: A target trial emulation.

BACKGROUND: Middle-aged and older adults with atopic dermatitis (AD) are at increased risk of dementia, possibly driven by chronic inflammation and involving IL-4 and IL-13 pathways. Whether treatment with dupilumab, an IL-4/IL-13 inhibitor, influences subsequent dementia risk in this population remains unclear. METHODS: This target trial emulation study utilized the TriNetX database. Patients aged ≥ 50 years with AD were identified and divided into two groups: those newly prescribed dupilumab and those newly prescribed conventional systemic agents without dupilumab exposure. Propensity score matching (1:1) was performed based on age, sex, race, and comorbidities. Dementia risk was assessed using Cox regression. RESULTS: After matching, each group included 10,039 patients (∼52% female; mean age, 63 years; 63% White). The 5-year cumulative incidence of dementia was lower among dupilumab users than controls (2.37% vs 3.33%; P = 0.001). Dupilumab use was associated with a reduced risk of all-cause dementia (HR 0.68; 95% CI, 0.54-0.86), with similar reductions observed across dementia subtypes, including secondary (HR 0.69; 95% CI, 0.48-0.99), unspecified (HR 0.70; 95% CI, 0.53-0.93), and Alzheimer's dementia (HR 0.61; 95% CI, 0.40-0.93). Subgroup and sensitivity analyses showed consistent results, with control outcome analyses supporting the robustness of the findings. In a validation analysis of middle-aged and older asthma patients, dupilumab users likewise had a lower dementia risk than omalizumab users (HR 0.68; 95% CI, 0.47-0.98). CONCLUSIONS: Dupilumab use was associated with a reduced risk of dementia in middle-aged and older adults with AD compared with conventional systemic agents.