Differential Pharmacodynamic Effects on Psoriatic biomarkers by Guselkumab Versus Secukinumab Correlate With Long-term Efficacy: an ECLIPSE substudy
JID Innovations, 2024
Blauvelt A., Chen Y., Branigan P., Liu X., DePrimo S., Keyes B., Leung M., Fakharzadeh S., Yang Y., Muñoz-Elías E., Krueger J., Langley R.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Immunological & Inflammatory Diseases Dermatological Diseases | Pathophysiology | Serum |  Olink Target 96 |
Abstract
Background
Interleukin (IL)-23, a cytokine produced by myeloid cells that drives T helper 17 (Th17) pathway and plays an essential role in the pathophysiology of plaque psoriasis. IL-23 activation initiates a cascade of cytokines subsequently inducing expression of many psoriasis-related proteins.
Objective
This study aimed to better understand underlying mechanisms driving differences between IL-23 and IL-17A blockade in patients with psoriasis and their implications for durability of clinical responses.
Design
Serum and/or skin biopsies were isolated from patients treated with guselkumab or secukinumab for evaluation of potential biomarkers of (pharmacodynamic) (PD) response to treatment.
Results
Guselkumab treatment led to significantly greater reductions of IL-17F and IL-22 serum levels compared with secukinumab at Weeks 24 and 48, demonstrating sustained regulation of the IL-23/Th17 pathway. Analyses of proteomic and transcriptomic profiles of patient sera and skin biopsies demonstrated differential regulation of proteins involved in chemokine, tumor necrosis factor, and relevant immune signaling pathways to a greater degree with guselkumab versus secukinumab treatment.
Conclusions
These data provide insights into differences between the mechanisms and impact of IL-23 versus IL-17A blockade in psoriasis, with implications for efficacy observations and treatment paradigms.