POS0657 GEOGRAPHIC VARIATION OF SAFETY IN THE FILGOTINIB RHEUMATOID ARTHRITIS PROGRAM
Authors: B. Combe, T. Matsubara, A. Pechonkina, Y. Tan, Z. Yin, J. Hong, R. Besuyen, A. Gomez-Centeno, M. H. Buch
Journal: Annals of the Rheumatic Diseases (2021)

Background: The Janus kinase-1 preferential inhibitor filgotinib (FIL) improved signs and symptoms of rheumatoid arthritis (RA) in the FIL clinical program. 1–3 Objectives: To assess FIL safety across regions. Methods: This was an analysis of patients (pts) meeting 2010 ACR/EULAR RA criteria in pooled phase (P)2 DARWIN 1–2 (D1–2), P3 FINCH 1–3 (F1–3), and long-term extension studies (DARWIN 3, FINCH 4). Data were analyzed by region: North America, South and Central America, Western Europe, Eastern Europe, Asia, South East (SE) Asia, and Other. Week (W)12 placebo (PBO)-controlled analysis included data from pts receiving once-daily FIL 100 mg (FIL100), FIL 200 mg (FIL200), or PBO for ≤12W (D1–2, F1–2); long-term as-treated data included pts from all 7 studies receiving FIL100 or FIL200; data after rerandomization were included and contributed to treatment received. Data presented as exposure-adjusted incidence rates (EAIRs)/100 patient-years of exposure (PYE) of treatment-emergent (TE) adverse events (TEAEs). Results: Table 1 shows EAIRs of TEAEs in PBO-controlled analysis. EAIRs/100 PYE of all TEAEs in Western Europe, Asia, and Other were higher than in remaining regions and for PBO vs FIL arms; EAIRs for FIL200/FIL100 in North America and SE Asia were higher vs PBO. EAIRs/100 PYE of TE serious AEs were higher in SE Asia for FIL100 and for FIL200/FIL100 in Other, with high PBO EAIRs in Western Europe. EAIRs/100 PYE of TEAEs leading to study discontinuation were higher in FIL arms vs PBO in Western Europe and Other (FIL200); in Asia and SE Asia, EAIRs were higher for PBO vs FIL200/FIL100. Table 1. EAIR of TEAEs (placebo-controlled) North America N = 481 South and Central America N = 350 Western Europe N = 141 Eastern Europe N = 933 Asia N = 236 South East Asia N= 135 Other N = 70 TEAE FIL200 a 216.9 (162.5, 289.5) 205.6 (155.1, 272.6) 285.0 (188.6, 430.8) 150.3 (119.3, 189.4) 248.9 (180.6, 343.1) 165.1 (104.0, 262.1) 298.4 (150.3, 592.5) FIL100 b 182.2 (136.8, 242.7) 159.2 (117.3, 216.1) 285.7 (183.7, 444.3) 146.4 (115.9, 185.0) 246.9 (180.3, 338.1) 153.7 (94.2, 251.0) 263.5 (113.9, 609.2) PBO C 174.5 (130.3, 233.7) 162.1 (118.8, 221.2) 314.9 (200.7, 493.9) 148.4 (117.6, 187.4) 259.0 (188.0, 356.8) 81.6 (40.8, 163.3) 306.0 (142.8, 655.7) TE serious AE FIL200 a 14.3 (6.0, 34.4) 11.4 (3.7, 35.5) 8.3 (1.2, 59.0) 12.2 (5.2, 28.7) 5.5 (0.8, 38.9) 0.0 (0.0, ∞) 49.6 (10.2, 144.9) FIL100 b 10.6 (4.0, 28.3) 7.2 (1.8, 28.7) 19.9 (5.0, 79.7) 15.1 (6.8, 33.7) 16.2 (5.2, 50.2) 28.8 (9.3, 89.4) 20.5 (0.5, 114.0) PBO C 16.1 (7.2, 35.9) 7.5 (1.9, 30.0) 29.6 (9.5, 91.7) 4.6 (1.3, 15.8) 11.4 (2.8, 45.5) 10.2 (1.4, 72.4) 0.0 (0.0, 69.2) TEAE leading to discontinuation FIL200 a 8.6 (2.8, 26.6) 3.8 (0.1, 21.2) 16.6 (4.2, 66.5) 12.9 (5.5, 30.5) 0.0 (0.0, 20.2) 9.2 (1.3, 65.1) 16.5 (0.4, 92.1) FIL100 b 10.6 (4.0, 28.3) 7.2 (0.9, 26.0) 19.9 (5.0, 79.7) 1.9 (0.2, 13.8) 5.4 (0.1, 30.1) 9.6 (1.4, 68.2) 0.0 (0.0, 75.5) PBO C 5.4 (1.3, 21.5) 0.0 (0.0, 13.8) 9.9 (1.4, 70.0) 12.9 (5.4, 30.7) 17.1 (3.5, 49.9) 20.4 (5.1, 81.6) 0.0 (0.0, 69.2) Data presented as EAIR (95% CI)/100 patient-years a N = 777, 179.8 PYE b N = 788, 181.6 PYE c N = 781, 178.4 PYE A subject may contribute to more than one treatment group if they received more than one treatment of interest. EAIR and corresponding 95% CI were estimated using Poisson regression model by treatment, including study and treatment with an offset of natural log of exposure time, except when 0 events occurred; Poisson model was not adjusted by study. AE, adverse event; CI, confidence interval; EAIR, exposure-adjusted incidence rate; FIL, filgotinib; PBO, placebo; PYE, patient-years of exposure; TE, treatment-emergent Figure shows serious infections (SI), venous thromboembolism (VTE) and herpes zoster (HZ) EAIRs. EAIRs for SI were highest in Other for FIL200 and SE Asia for FIL100. While VTE EAIRs were low, pts in 5/7 regions had VTE. HZ EAIRs were highest in Asia. Conclusion: Although EAIR of TEAEs varied between regions, no consistent trend was reflected in any particular region. References: [1]Genovese et al. JAMA . 2019;322:315–25. [2]Westhovens et al. Ann Rheum Dis . 2021; online first. [3]Combe et al. Ann Rheum Dis . 2021; online first. Disclosure of Interests: Bernard Combe Speakers bureau: BMS; Eli Lilly &amp; Co.; Gilead Sciences, Inc.; MSD; Pfizer; Roche-Chugai; and UCB, Consultant of: AbbVie; Eli Lilly &amp; Co.; Gilead Sciences, Inc.; Janssen; Pfizer; Roche-Chugai; and Sanofi, Grant/research support from: Novartis, Pfizer, and Roche-Chugai, Tsukasa Matsubara Speakers bureau: Pfizer Japan, Nichi-Iko, Astellas, Meiji Seika, Bristol-Myers Squibb, AbbVie GK, Janssen, Chugai, Eisai, AYUMI, Alena Pechonkina Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., YingMeei Tan Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Zhaoyu Yin Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Jaehyung Hong Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Robin Besuyen Shareholder of: Galapagos, BV, Employee of: Galapagos, BV, Antonio Gomez-Centeno Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly &amp; Co., Gebro, Janssen, Menarini, Merck Sharp &amp; Dohme, Pfizer, Roche, Rubio, Sanofi, and UC, Consultant of: AbbVie, Biogen, Bristol-Myers Squibb, Celgene, Eli Lilly &amp; Co., Gebro, Gilead Sciences, Inc., Hospira, Merck Sharp &amp; Dohme, Pfizer, Roche, Rubio, Sandoz, Sanofi, Grant/research support from: Boehringer Ingelheim, Celltrion, Eli Lilly &amp; Co., Galapagos NV, Gilead Sciences, Inc., Novartis, Pfizer, Roche, Sanofi, UCB, YL Biologics, Maya H Buch Speakers bureau: AbbVie; Eli Lilly and Company; Gilead Sciences, Inc.; Merck-Serono; Pfizer; Roche; Sandoz; Sanofi; and UCB, Consultant of: AbbVie; Eli Lilly and Company; Gilead Sciences, Inc.; Merck-Serono; Pfizer; Roche; Sandoz; Sanofi; and UCB, Grant/research support from: AbbVie; Eli Lilly and Company; Gilead Sciences, Inc.; Merck-Serono; Pfizer; Roche; Sandoz; Sanofi; and UCB