Clinical efficacy and endotype changes in Chinese atopic dermatitis patients after abrocitinib treatment

Summary: Abstract Body: Phase 3 trials have demonstrated the efficacy and safety of abrocitinib for atopic dermatitis (AD), but real-world evidence remains limited. This prospective study enrolled 117 moderate-to-severe AD patients, and physician- and patient-reported outcomes were evaluated at multiple time points. Blood eosinophil counts, serum IgE, 24 cytokines/chemokines, and blood cell mRNA sequencing were measured. Abrocitinib treatment led to rapid and potent improvements in disease severity. At week 12, 74.3% and 50.5% of AD patients achieved at least 75% and 90% improvement in the eczema area and severity index (EASI), respectively. Compared to dupilumab, abrocitinib showed greater improvement in Itch-NRS at week 2 and a higher proportion of EASI-75 at week 4. Adverse events occurred in 42.7% of AD patients, with gastrointestinal symptoms being the most common (17.1%). No tuberculosis (TB) reactivation was observed in patients who screened positive for TB and received isoniazid prophylaxis during the study period. Lower body mass index (BMI < 24; adjusted OR: 4.01, 95%CI: 1.36–11.73) and no prior dupilumab use (adjusted OR: 5.81, 95%CI: 1.8–18.7) were identified as predictors of a good response. By week 4, blood eosinophil counts and serum IgE significantly decreased. Reductions in Th2-, Th1-, and Treg-related cytokines/chemokines after 4 weeks of abrocitinib treatment, including IL-5, CCL17, CCL18, TNF-α, IL-6, IL-10, and CD25/IL-2Rα, were more pronounced in good responders. Correspondingly, blood transcriptome normalization, including downregulation of Th2, Th1, eosinophil, and an increase in Tr1 cell abundance, rapidly occurred by week 4, with slight rebound by week 12. WGCNA identified an efficacy-related gene module, leading to a five-gene (PLN2, CAT, CLC, RAB44, SMPD3) efficacy-predictive model. In conclusion, Abrocitinib demonstrated robust efficacy and a well-tolerated safety profile in Chinese patients with moderate-to-severe AD in routine clinical practice, accompanied by normalization of elevated blood biomarkers and dysregulated blood transcripts. Zheng Li¹, Yuemeng Wu¹, Yu Wang¹, Chaoying Gu¹, Wei Li¹ 1. Huashan Hospital Fudan University, Shanghai, Shanghai, China. Clinical Research: Epidemiology and Observational Research