POS0446 FILGOTINIB-TREATED RHEUMATOID ARTHRITIS PATIENTS WITH HIGH BASELINE NEUTROPHIL-TO-LYMPHOCYTE RATIO SHOW BETTER CLINICAL RESPONSE RATES AND PATIENT-REPORTED OUTCOMES
Authors: P. C. Taylor, B. Downie, S. Kim, R. Hawtin, R. Moots, T. Takeuchi
Journal: Annals of the Rheumatic Diseases (2021)

Background: Rheumatoid arthritis (RA) is a systemic inflammatory disease which includes increased innate and myeloid immune cell activation. Filgotinib (FIL), an oral JAK1 inhibitor, has shown safety and efficacy in three phase 3 studies (FINCH1-3) in adults with moderately-to-severely active RA. The baseline (BL) neutrophil-to-lymphocyte ratio (NLR) in RA has been associated with a positive response to anti-tumor necrosis factor (TNF) therapy 1 and a negative response to DMARD triple therapy 2 . We previously reported a BL signature of clinical response in the FINCH2 (bDMARD-IR) population which included a neutrophil component 3 . Objectives: We conducted a post-hoc analysis to explore whether the BL NLR was associated with response to treatment in the FINCH studies. Methods: Clinical data of 3273 RA patients (pts) enrolled in the FINCH clinical trials (FINCH3, methotrexate (MTX)-naïve: NCT02886728 ; FINCH1, MTX-Inadequate Responder (IR): NCT02889796 ; FINCH2, bDMARD-IR: NCT02873936 ) were retrospectively analyzed for a relationship between the BL NLR and composite clinical endpoints (ACR-N, DAS28CRP, or CDAI) or PROs (Pain VAS, FACIT Fatigue, HAQ-DI) through week 24. Pts were classified as High or Low BL NLR using a cutpoint (2.7) identified as an independent predictor of treatment failure in a published RA study 2 . Adjusted clinical outcomes were estimated based on mixed effects linear regression models including geographic region and demographics covariates. Results: 57% of pts enrolled in the FINCH trials were classified as BL NLR-High (Table 1) and FINCH3 NLR-High pts showed higher BL DAS28(CRP). FINCH1 and FINCH3 FIL+MTX-arm NLR-High pts demonstrated significantly better DAS28(CRP) response compared to NLR-Low pts (Figure 1). DAS28(CRP) differences between NLR-High and NLR-Low were detectable as early as Week 2 for FIL200mg + MTX and were sustained through Week 24. FINCH1 and FINCH3 FIL200mg + MTX NLR-High pts also demonstrated sustained clinical and PRO improvements over NLR-Low, including CDAI, ACR-N, Pain VAS, FACIT Fatigue, and HAQ-DI. The strength of these associations was dose-dependent; pts that received FIL100mg + MTX demonstrated weaker but directionally consistent trends in both populations. No significant association between NLR subgroup and clinical efficacy was observed in FINCH2 FIL+MTX-arm pts, FIL-monotherapy (FINCH3) pts, or adalimumab+MTX (FINCH1) pts. Conclusion: In FINCH1 (MTX-IR) and FINCH3 (MTX-naïve), FIL200mg + MTX -arm NLR-High pts demonstrate better sustained clinical response and PRO scores compared to NLR-Low pts. These data are the first to report an association between the BL NLR and therapeutic response in large randomized RA clinical trials. Future studies on pathobiologies reflected by the NLR biomarker may clarify its potential to guide RA disease management. References: [1]Farutin V. Arthritis Res Ther. 2019. [2]Boulos D. Semin Arthritis Rheum. 2019. [3]Taylor P. Arthritis Rheumatol. 2019; 71 (suppl 10). Table 1. Demographics of patients enrolled in FINCH clinical trials by baseline NLR category. NLR-Low (NLR &lt; 2.7 ) (N=1407, 43%) NLR-High (NLR &gt; 2.7 ) (N=1866, 57%) Total (N=3273, 100%) P-value Age at enrollment 0.668 2 Mean (SD) 53.00 (12.74) 53.19 (13.24) 53.11 (13.02) Female 1,157 (82.2%) 1,448 (77.6%) 2,605 (79.6%) 0.001 1 Seropositivity 1,073 (76.3%) 1,575 (84.4%) 2,648 (80.9%) &lt; 0.001 1 Prior bDMARD # Mean (SD) 0.23 (0.73) 0.28 (0.82) 0.26 (0.78) 0.037 2 Duration of RA Mean (SD) 5.93 (7.39) 6.61 (8.07) 6.32 (7.79) 0.013 2 Baseline oral corticosteroid 537 (38.2%) 895 (48.0%) 1,432 (43.8%) &lt; 0.001 1 Baseline DAS28(CRP) 5.55 (0.90) 5.89 (0.97) 5.74 (0.95) 0.001 2 Baseline HAQ-DI 1.53 (0.60) 1.62 (0.65) 1.58 (0.63) 0.001 2 1 Pearson’s Chi-squared test. 2 Linear Model ANOVA. Figure 1. Association of BL NLR with DAS28(CRP). Dots represent DAS28(CRP) estimate from a fully adjusted mixed-effects model, shaded area shows the 95% confidence interval. Outlined circles and proximal text show significantly different values between NLR-High and NLR-Low. Disclosure of Interests: Peter C. Taylor Consultant of: AbbVie, Biogen, Galapagos, Gilead, GlaxoSmithKline, Janssen, Lilly, BMS, Pfizer, Roche, Celltrion, Sanofi, Nordic Pharma, Fresenius and UCB, Grant/research support from: Celgene, Galapagos, Gilead, Lilly., Bryan Downie Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Sam Kim Shareholder of: Gilead Science, Employee of: Gilead Sciences, Rachael Hawtin Shareholder of: Gilead Sciences, Employee of: Gilead Sciences, Robert Moots Speakers bureau: Amgen, Chugai, Gilead, Libbs, Pfizer, Roche, Consultant of: Amgen, Chugai, Novartis, Pfizer, Roche, Grant/research support from: AKL, Novartis, UCB Pharma, Tsutomu Takeuchi Speakers bureau: AbbVie, Eisai Co. Gilead Sciences, Sanofi K.K. Mitsubishi-Tanabe Pharma Corp. Chugai Pharmaceutical Co, Ltd., Eli Lilly Japan,Novartis., Bristol-Myers Squibb., Janssen Pharmaceutical K.K., Consultant of: Astellas Pharma, Inc. AbbVie, Gilead Sciences, Eli Lilly Japan, Novartis, Mitsubishi-Tanabe Pharma Corp. Chugai Pharmaceutical Co, Ltd. Pfizer Japan Inc. Janssen Pharmaceutical K.K., Grant/research support from: Asahikasei Pharma Corp.AbbVie, AYUMI Pharmaceutical Co. Eisai Co., ONO Pharmaceutical Co,LTD.,Sanofi K.K. Mitsubishi-Tanabe, Daiichi Sankyo Co., Chugai Pharmaceutical Co, Ltd. Eli Lilly Japan, Nippon Boehringer lngelheim Co., Ltd.,UCB JAPAN, DNA Chip Research Inc.