P643 Filgotinib decreases systemic and mucosal markers of inflammation that are associated with endoscopic improvement in moderately to severely active Crohn’s disease patients

Abstract

Background: Filgotinib is a JAK1-selective inhibitor currently being evaluated in Phase III clinical studies for treatment of ulcerative colitis and Crohn's disease (CD). In a Phase II study in patients with moderately to severely active CD (FITZROY, ClinicalTrial.gov ID =50% decrease from baseline in SES-CD score) was assessed by AUROC. Result(s): Baseline biomarker levels were comparable between placebo and filgotinib treatment groups, except IL-17A and VEGF-A which were higher in placebo- (medians at 3.2 and 547.2 pg/mL) versus filgotinib treatment group (1.3 and 389.6 pg/mL, p<0.05). Filgotinib treatment induced reductions in fecal calprotectin (median % change of -30% to -35%), serum IL-6 (-11% to -20%) and serum VEGF-A (-8% to -12%) at all time points. Decline in fecal calprotectin, CRP and VEGF-A in filgotinib-treated patients was observed as early as Week 2 and was significant compared to placebo-treated patients (p<0.05). No significant treatment effect was observed for IL-10, IFN-gamma and IL-8. No significant change in fecal calprotectin, serum CRP and serum cytokines was observed in placebo-treated patients. In filgotinib-treated patients, a significant association was observed between the decrease in both systemic (serum CRP and IL-6) and mucosal (stool calprotectin) biomarkers and endoscopic response (Table 1).Copyright © 2018 AGA Institute. All rights reserved.