Inhibición Preferencial de JAK1 en Relación a JAK 3 por Upadacitinib: Análisis de la Exposición-Respuesta de Datos Ex Vivo en 2 Ensayos Clínicos Fase 1 y Comparación con Tofacitinib
Pharmacodynamics. 2020
Ex vivo pharmacodynamic assay results demonstrated a greater selectivity of UPA on JAK1 versus JAK3 compared to TOF. This analysis conducted ex vivo stimulation of STAT3 phosphorylation by IL-6 as a measure of JAK1 activity and STAT5 phosphorylation by IL-7 as a measure of JAK1/JAK3 activity. Change in pSTAT3 and pSTAT5 were calculated at 1, 6 and 12 hours following drug administration using samples collected from healthy subjects and subjects with RA, from 2 phase 1 studies. Exposure-response m...