In vivo, Filgotinib demonstrates potent disease-modifying activity in a therapeutic rat model of collagen-induced arthritis (CIA), with oral dosing (3, 10, 30 mg/kg) effectively halting disease progression. At a higher dosage (50 mg/kg, orally), it protects against bone and cartilage damage, significantly reduces T-cell and macrophage infiltration in affected tissues, and lowers serum levels of key inflammatory markers and chemokines, such as IL-6, IP-10, XCL1, and MCP-1. Its efficacy is also evident at lower doses (0.1 and 0.3 mg/kg), further highlighting its therapeutic potential^[1][2].

Filgotinib, identified as GLPG0634, selectively inhibits the differentiation of Th2 cells by interfering with IL-4 signaling, which is mediated through JAK1 and JAK3, showcasing dose-dependent efficacy at concentrations of 1 μM or lower. This action also extends to Th1 cell differentiation, indicating its broad immunomodulatory potential^[1].

Remarkably, Filgotinib does not impact JAK2 homodimer-mediated pathways triggered by erythropoietin (EPO) or prolactin (PRL), with its IC50 exceeding 10 μM. This specificity underscores its targeted approach in modulating immune responses without affecting certain critical hematopoietic signals^[2].