D2.266 - Comparative Efficacy of Dupilumab, Janus Kinase Inhibitors, and Conventional Immunosuppressants on Neuropsychiatric Outcomes in Patients with Atopic Dermatitis: A Retrospective Cohort Study

Atopic dermatitis is associated with substantial neuropsychiatric comorbidity. Comparative data on psychiatric outcomes among patients treated with dupilumab, Janus kinase inhibitors, and conventional systemic immunosuppressants are lacking. Thus we aimed to compare neuropsychiatric disorder incidence in patients with atopic dermatitis receiving dupilumab, Janus kinase inhibitors, or conventional immunosuppressants.

This retrospective cohort study utilized the TriNetX global health research network. Three propensity score-matched cohorts were established: Janus kinase inhibitors versus dupilumab (n=608 per group), conventional immunosuppressants versus Janus kinase inhibitors (n=502 per group), and conventional immunosuppressants versus dupilumab (n=2,322 per group). The primary outcome was incident psychiatric disorder diagnosis within 2 years.

Janus kinase inhibitors (hazard ratio 0.51, 95% confidence interval 0.30-0.87) and dupilumab (hazard ratio 0.79, 95% confidence interval 0.63-0.99) were each associated with significantly lower psychiatric disorder risk compared with conventional immunosuppressants. Janus kinase inhibitors demonstrated 38% relative risk reduction compared with dupilumab (hazard ratio 0.62, 95% confidence interval 0.37-1.03). Janus kinase inhibitors reduced anxiety disorder risk by 50% compared with conventional therapy (hazard ratio 0.50, 95% confidence interval 0.28-0.89), whereas dupilumab did not achieve statistical significance. Dupilumab was associated with 80% lower autistic disorder risk compared with conventional therapy (hazard ratio 4.84, 95% confidence interval 1.04-22.44).

Janus kinase inhibitors and dupilumab each demonstrate superior neuropsychiatric safety profiles compared with conventional immunosuppressants in patients with atopic dermatitis, with Janus kinase inhibitors showing the most favorable outcomes.