FRI0092 SAFETY AND EFFICACY OF FILGOTINIB IN ACTIVE RHEUMATOID ARTHRITIS BY PRIOR BIOLOGICAL DMARD EXPOSURE IN PATIENTS WITH PRIOR INADEQUATE RESPONSE OR INTOLERANCE TO BIOLOGICAL DMARDS (BDMARD-IR)

Background Filgotinib (FIL), an oral selective Janus kinase 1 (JAK1) inhibitor, significantly improved the signs and symptoms of rheumatoid arthritis (RA) with a favorable safety profile in a global phase 3 study in bDMARD-IR patients with active RA (FINCH2).1 Objectives To assess the safety and efficacy of FIL in the FINCH2 study by the number and type of prior bDMARDs. Methods FINCH2 enrolled 449 bDMARD-IR patients with moderate-to-severe active RA. Patients were randomized 1:1:1 to FIL 200 mg, FIL 100 mg or placebo (PBO) on a background of csDMARDs for 24 weeks. In this prespecified subgroup analysis, efficacy and safety were analyzed according to the number (<3 vs ≥3) of previous bDMARDs used. Results 448 patients received ≥1 dose of study drugs. Of these, 343 were previously exposed to <3 bDMARDs, while 105 were previously exposed to ≥3 bDMARDs. Table 1 shows demographics and baseline (BL) characteristics of patients in these 2 groups; efficacy and safety parameters (Table 2) were similar for both groups. There were no cases of opportunistic infection, active tuberculosis, malignancy, gastrointestinal perforation, or death.Table 1 BL Demographics and characteristics <3 bDMARDs (n=343) ≥3 bDMARDs (n=105) FIL 200(n=110) FIL 100(n=119) PBO(n=114) FIL 200(n=37) FIL 100(n=34) PBO(n=34) Female, n (%) 90 (82) 92 (77) 93 (82) 30 (81) 27 (79) 28 (82) Mean (SD) age, yrs 54 (13) 55 (13) 56 (12) 59 (9) 54 (9) 56 (12) Concurrent steroids, n (%) 46 (42) 49 (41) 54 (47) 22 (60) 19 (56) 17 (50) Concurrent MTX, n (%) 98 (89) 101 (85) 96 (84) 26 (70) 26 (77) 20 (59) Mean (SD) DAS28(CRP) 6.0 (1.0) 5.8 (1.0) 5.9 (0.9) 5.8 (1.0) 6.1 (1.0) 5.9 (0.9) Mean (SD) HAQ-DI 1.66 (0.65) 1.62 (0.70) 1.63 (0.65) 1.84 (0.66) 1.72 (0.61) 1.74 (0.57) Mean (SD) hsCRP (mg/L) 17.04 (16.80) 21.82 (28.49) 16.08 (19.16) 17.70 (22.36) 20.31 (27.58) 17.56 (15.37)Table 2 Key week 24 efficacy and safety outcomes <3 bDMARDs (n=343) ≥3 bDMARDs (n=105) FIL 200(n=110) FIL 100(n=119) PBO(n=114) FIL 200(n=37) FIL 100(n=34) PBO(n=34) ACR20 n (%)a Δ34.9% Δ21.2% Δ35.2% Δ17.6% DAS28(CRP)≤3.2 n (%)a Δ27.3% Δ15.8% Δ29.0% Δ20.6% DAS28(CRP)<2.6 n (%)a Δ19.6% Δ12.9% Δ15.7% Δ17.6% HAQ-DI mean CFB (SD) –0.74 (0.631)‡ –0.61 (0.668)* –0.42 (0.618) –0.77 (0.596)† –0.54 (0.635) –0.44 (0.525) SF-36 PCS mean CFB (SD) 9.4 (8.45)† 8.9 (8.72)* 6.4 (8.44) 9.4 (7.65) 9.1 (7.36) 7.2 (5.44) FACIT-Fatigue mean CFB (SD) 11.3 (11.99)† 9.7 (10.44)* 6.7 (10.68) 12.6 (10.78)‡ 10.2 (10.42)† 8.4 (8.12) TEAE 75 (68.2%) 73 (61.3) 76 (66.7%) 27 (73.0%) 24 (70.6%) 24 (70.6%) TEAE leading to study drug discontinuation 4 (3.6%) 3 (2.5%) 2 (1.8%) 1 (2.7%) 3 (8.8) 1 (2.9%) CFB, change from BL. *p<0.05, †p<0.01, ‡p<0,001; Δ, difference vs PBO. aFIL values are PBO-corrected. Conclusion In bDMARD-IR patients with active RA, FIL treatment for 24 weeks significantly improved the signs and symptoms of RA with a favorable safety profile; notably, efficacy and safety results were similar for patients with <3 or ≥3 prior bDMARDs. Reference [1] Genovese MC, et al. ACR 2018. Abstract L06. Disclosure of Interests Mark C. Genovese Grant/research support from: Sanofi/Genzyme, Genentech/Roche, RPharm, Consultant for: Sanofi/Genzyme, Genentech/Roche, RPharm, Kenneth Kalunian Grant/research support from: Gilead Sciences, Inc., Jacques-Eric Gottenberg Grant/research support from: Bristol-Myers Squibb, Grant/research support from: Bristol-Myers Squibb, Consultant for: Bristol-Myers Squibb, Lilly, Pfizer, Sanofi-Genzyme, UCB Pharma, Consultant for: Bristol-Myers Squibb, Eli Lilly, UCB, Sanofi-Genzyme, Pfizer, Neelufar Mozaffarian Shareholder of: Gilead, Employee of: Gilead, Beatrix Bartok Shareholder of: Gilead, Employee of: Gilead, Franziska Matzkies Shareholder of: Gilead, Employee of: Gilead, Jie Gao Shareholder of: Gilead, Employee of: Gilead, Ying Guo Shareholder of: Gilead, Employee of: Gilead, Kurt de Vlam Consultant for: Pfizer Inc, Consultant for: Johnson & Johnson, David Walker: None declared, Tsutomu Takeuchi Grant/research support from: Astellas Pharma Inc, Chugai Pharmaceutical Co, Ltd., Daiichi Sankyo Co., Ltd., Takeda Pharmaceutical Co., Ltd., AbbVie GK, Asahikasei Pharma Corp., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Eisai Co., Ltd., AYUMI Pharmaceutical Corporation, Nipponkayaku Co. Ltd., Novartis Pharma K.K., Grant/research support from: AbbVie, Asahi Kasei, Astellas, AstraZeneca, AYUMI, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Eli Lilly Japan, Janssen, Mitsubishi Tanabe, Nippon Kayaku, Novartis, Pfizer Japan Inc, Taiho, Taisho Toyama, Takeda, Teijin, Grant/research support from: Astellas Pharma Inc., Bristol Myers Squibb, Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Santen Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd., AbbVie GK, Asahi Kasei Pharma Corp., Taisho Toyama Pharmaceutical Co., Ltd., SymBio Pharmaceuticals Ltd., Janssen Pharmaceutical K.K., Celltrion Inc., Nipponkayaku Co. Ltd., and UCB Japan, Consultant for: Astra Zeneca K.K., Eli Lilly Japan K.K., Novartis Pharma K.K., Mitsubishi Tanabe Pharma Co., Abbivie GK, Nipponkayaku Co.Ltd, Janssen Pharmaceutical K.K., Astellas Pharma Inc., Taiho Pharmaceutical Co. Ltd., Chugai Pharmaceutical Co. Ltd., Taisho Toyama Pharmaceutical Co. Ltd., GlaxoSmithKline K.K., UCB Japan Co. Ltd., Consultant for: AbbVie, Asahi Kasei, Astellas, AstraZeneca, AYUMI, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Eli Lilly Japan, Janssen, Mitsubishi Tanabe, Nippon Kayaku, Novartis, Pfizer Japan Inc, Taiho, Taisho Toyama, Takeda, Teijin, Consultant for: Astra Zeneca K.K., Eli Lilly Japan K.K., Novartis Pharma K.K., Mitsubishi Tanabe Pharma Co., Asahi Kasei Medical K.K., AbbVie GK, Daiichi Sankyo Co., Ltd., Bristol Myers Squibb, and Nipponkayaku Co. Ltd., Speakers bureau: Astellas Pharma Inc., Bristol Myers Squibb, Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Santen Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd., AbbVie GK, Asahi Kasei Pharma Corp., Taisho Toyama Pharmaceutical Co., Ltd., SymBio Pharmaceuticals Ltd., Janssen Pharmaceutical K.K., Celltrion Inc., Nipponkayaku Co. Ltd., and UCB Japan, Speakers bureau: AbbVie, Asahi Kasei, Astellas, AstraZeneca, AYUMI, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Eli Lilly Japan, Janssen, Mitsubishi Tanabe, Nippon Kayaku, Novartis, Pfizer Japan Inc, Taiho, Taisho Toyama, Takeda, Teijin, Speakers bureau: AbbVie GK., Bristol–Myers K.K., Chugai Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Astellas Pharma Inc, Diaichi Sankyo Co. Ltd., Eisai Co. Ltd., Sanofi K.K., Teijin Pharma Ltd., Takeda Pharmaceutical Co. Ltd., Novartis Pharma K.K.