Longitudinal Proteomic Signatures of Dupilumab and Tralokinumab Treated Atopic Dermatitis Patients.

BACKGROUND

Atopic dermatitis (AD) is a chronic inflammatory disease driven by Type 2 (Th2) inflammation. Dupilumab (anti-IL-4Rα) and tralokinumab (anti-IL-13) are effective biologic therapies, but a direct comparison of their longitudinal effects on the systemic proteome is lacking. This exploratory study aimed to identify and to differentially analyze the proteomic signatures in AD patients treated with dupilumab versus tralokinumab.

METHODS

In this prospective, observational study, serum samples were collected from patients with moderate-to-severe AD at baseline and after 12 months of treatment with either dupilumab (n = 10) or tralokinumab (n = 10). A cohort of healthy controls (n = 12) was included for baseline comparison. Proteomic profiling was performed using a targeted 440-protein array, and data were analyzed for differential expression and pathway enrichment.

RESULTS

At baseline, AD patients exhibited a distinct proteomic signature compared to healthy controls, characterized by a strong Th2 inflammatory profile and enrichment of the IL-4/IL-13 signaling pathway. After 12 months, both therapies reduced the core Th2 inflammatory signature with downregulation of key markers like CCL17. Dupilumab induced a broader immunomodulation, showing a more pronounced upregulation of Th1 associated proteins compared to tralokinumab. Furthermore, the therapies had opposing effects on tissue repair and metabolic proteins; dupilumab treatment led to a decrease in TNFSF11 and Sclerostin (SOST), while these were increased after tralokinumab treatment.

CONCLUSION

Dupilumab and tralokinumab effectively target the Th2 axis in AD but their longitudinal systemic immune modulation differs in respect to Th1-Th17 and tissue repair markers.