THU0031 FILGOTINIB TREATMENT PROVIDES RAPID AND SUSTAINED REDUCTION OF INFLAMMATORY BIOMARKERS IN MODERATE TO SEVERE PSORIATIC ARTHRITIS (PSA) PATIENTS

Background PsA is a chronic inflammatory musculoskeletal disease characterized by joint and skin inflammation, enthesitis, dactylitis, and nail lesions. In the recent EQUATOR study, filgotinib (FIL), an oral, selective Janus kinase 1 (JAK1) inhibitor, produced significant and sustained improvements on the signs and symptoms of PsA compared to placebo (PBO).1 As targeted JAK1 inhibition by FIL has potential to simultaneously block multiple inflammatory pathways, we analyzed biomarker samples from EQUATOR using exploratory multiplex biomarker panels. Objectives To evaluate the impact of targeted JAK1 inhibition on the circulating biomarkers in patients with active PsA. Methods Design and results of the EQUATOR study—a 16-week, double-blind, multicenter, phase 2 study in subjects with active PsA (NCT03101670)—have been published.1 Subjects were randomized 1:1 to 200 mg FIL (n=65) or PBO (n=66) once daily. Serum samples (FIL n=60 and PBO n=61) were collected at baseline (BL), week 1, week 4, and week 16, and analyzed using 135 multiplex biomarker screening panels. Biomarker changes from BL were analyzed on all time-paired subject data and reported for weeks 1, 4, and 16. Results FIL treatment produced significant reductions serum concentration of multiple biomarkers associated with PsA disease activity. We identified 4 clusters of biomarker response based on the kinetics and magnitude of changes from BL (Figure); Cluster 1: rapid, substantial and sustained reduction (>25% from BL by week 1); Cluster 2: rapid and moderate reduction (5%–15% from BL by week 1); Cluster 3: delayed reduction (significant reduction by week 4); and Cluster 4: moderate increase (5%–10% from BL). Although initial grouping was based on the speed and magnitude of biomarker response, a number of biomarkers formed subclusters representing discrete biological functions. Cluster 1 included 2 acute phase reactants (CRP, SAA) while Cluster 2 included inflammatory mediators (TNFR1, CXCL10, IL-12/-23; CXCL10 and IL-12/-23 reached full reduction by week 1). Cluster 3 was the largest group and represented biomarkers of matrix remodeling (MMP1, TIMP1), cell adhesion (ICAM-1, E-selectin), and angiogenesis (VEGF-A). Cluster 4 had biomarkers related to diverse functions (Eotaxin, CEA, adiponectin). Conclusion In patients with active PsA, FIL treatment significantly decreased levels of circulating biomarkers, including acute-phase reactants, proinflammatory cytokines and chemokines, and various adhesion molecules. These data support the idea that FIL treatment results in rapid and sustained reduction of the inflammatory milieu present in autoimmune inflammatory diseases, consistent with efficacy previously reported for this study.1 Reference [1] Mease PJ, et al. Lancet. 2018;392:2367-2377. Disclosure of Interests Dafna D Gladman Grant/research support from: AbbVie, Amgen, Celgene, Lilly, Novartis, Pfizer, and UCB, Consultant for: AbbVie, Amgen, BMS, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB, Rene Galien Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Corrine Jamoul Employee of: Galapagos NV, Mona Trivedi Shareholder of: Amgen and Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Neelufar Mozaffarian Shareholder of: Gilead, Employee of: Gilead, OhKyu Yoon Shareholder of: Gilead Sciences, Inc., Amgen, Employee of: Gilead Sciences, Inc., Amgen, Wendy Jiang Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., JiYun Kim Shareholder of: Gilead Sciences, Inc., Employee of: Bayer Healthcare, LLC, Gilead Sciences, Inc.