THU0204 A SUBGROUP ANALYSIS OF LOW DISEASE ACTIVITY AND REMISSION FROM PHASE 3 STUDY OF FILGOTINIB IN PATIENTS WITH INADEQUATE RESPONSE TO BIOLOGIC DMARDS
Authors: J. E. Gottenberg, M. H. Buch, R. Caporali, G. C. Wright, T. Takeuchi, K. Kalunian, A. Pechonkina, Y. Guo, S. Rao, Y. Tan, R. Besuyen, M. C. Genovese
Journal: Annals of the Rheumatic Diseases (2020)

Background: Despite effective treatments, many patients (pts) with rheumatoid arthritis (RA) have inadequate responses to biologic DMARDs (bDMARD-IR), highlighting an unmet need. It is unclear whether prior bDMARD use affects efficacy of the oral, selective JAK-1 inhibitor filgotinib (FIL). Objectives: To explore clinical response to FIL in bDMARD-IR pts stratified by mode of action (MOA) and number of prior bDMARDs. Methods: The global, phase 3 FINCH-2 ( NCT02873936 ) study treated 448 bDMARD-IR pts with active RA. 1 Pts were randomised 1:1:1 to once-daily FIL 200 mg, FIL 100 mg, or placebo (PBO) for 24 weeks. Efficacy was assessed by percent of pts achieving low disease activity (LDA) or remission at week (W)24 as measured by CDAI and DAS28(CRP) stratified by number and MOA of prior bDMARDs. Comparisons were not adjusted for multiplicity. Nonresponder imputation was used. Results: In total, 448 bDMARD-IR pts were included, 105 with prior experience with ≥3 bDMARDs ( Table ). At W24, pts receiving FIL were in LDA at a higher proportion vs PBO, irrespective of number of prior bDMARDs or MOA (Figure 1). For pts receiving FIL 200 vs PBO, DAS28(CRP) ≤3.2 was achieved at W24 by 52% vs 26%, 51% vs 22%, and 38% vs 9% of pts with 1, 2, or ≥3 prior bDMARDs, respectively, and 49% vs 21% and 50% vs 13% of pts exposed to TNF or IL-6 inhibitors; for all subgroups, rates were significantly higher vs PBO (Figure 1). Delta between FIL 200 mg and PBO was maintained irrespective of number or type of prior bDMARDs. At W24, pts receiving FIL achieved remission at numerically higher rates vs PBO (Figure 2). For pts receiving FIL 200 mg vs PBO, DAS28(CRP) &lt;2.6 was achieved at W24 by 36% vs 14%, 30% vs 14%, and 22% vs 6% of pts with 1, 2, and ≥3 prior bDMARDs, respectively, and 31% vs 14% and 29% vs 9% of pts exposed to TNF or IL-6 inhibitors (Figure 2). Delta between FIL 200 mg and PBO was maintained irrespective of number or type of prior bDMARDs. Treatment-emergent adverse events across subgroups were consistent with overall study population. Table. Number and MOA of prior bDMARDs FIL 200 mg n = 147 FIL 100 mg n = 153 PBO n = 148 Total N = 448 Prior bDMARDs 1 73 (49.7) 86 (56.2) 77 (52.0) 236 (52.7) 2 37 (25.2) 33 (21.6) 36 (24.3) 106 (23.7) ≥3 37 (25.2) 34 (22.2) 34 (23.0) 105 (23.4) LOE ≥1 bDMARD 125 (85.0) 129 (84.3) 126 (85.1) 380 (84.8) Intolerance ≥1 bDMARD 36 (24.5) 34 (22.2) 32 (21.6) 102 (22.8) Prior TNFi 121 (82.3) 134 (87.6) 124 (83.8) 379 (84.6) LOE ≥1 TNFi 97 (66.0) 113 (73.9) 103 (69.6) 313 (69.9) Intolerance ≥1 TNFi 25 (17.0) 24 (15.7) 24 (16.2) 73 (16.3) Prior non-TNFi 73 (49.7) 62 (40.5) 75 (50.7) 210 (46.9) LOE ≥1 non-TNFi 52 (35.4) 43 (28.1) 56 (37.8) 151 (33.7) Intolerance ≥1 non-TNFi 13 (8.8) 13 (8.5) 11 (7.4) 37 (8.3) Prior IL-6i 34 (23.1) 35 (22.9) 32 (21.6) 101 (22.5) LOE ≥1 IL-6i 25 (17.0) 22 (14.4) 21 (14.2) 68 (15.2) Intolerance ≥1 IL-6i 5 (3.4) 10 (6.5) 5 (3.4) 20 (4.5) Data presented as n (%). i, inhibitor; LOE, lack of efficacy. Conclusion: Treatment with FIL vs PBO led to higher rates of LDA and remission in pts with IR to IL-6 or TNF inhibition, or to 1, 2, or ≥3 prior bDMARDs, with a similar safety profile to the overall study population. A significantly higher proportion of pts overall receiving FIL 200 mg vs PBO were in LDA at W24. Improved efficacy of FIL vs PBO in pts who previously failed multiple bDMARDs indicates distinct benefits of selective JAK-1 inhibition with FIL. References: [1]Genovese, et al. JAMA 2019;322(4):315–25. Disclosure of Interests: : Jacques-Eric Gottenberg Grant/research support from: BMS, Pfizer, Consultant of: BMS, Sanofi-Genzyme, UCB, Speakers bureau: Abbvie, Eli Lilly and Co., Roche, Sanofi-Genzyme, UCB, Maya H Buch Grant/research support from: Pfizer, Roche, and UCB, Consultant of: Pfizer; AbbVie; Eli Lilly; Gilead Sciences, Inc.; Merck-Serono; Sandoz; and Sanofi, Roberto Caporali Consultant of: AbbVie; Gilead Sciences, Inc.; Lilly; Merck Sharp &amp; Dohme; Celgene; Bristol-Myers Squibb; Pfizer; UCB, Speakers bureau: Abbvie; Bristol-Myers Squibb; Celgene; Lilly; Gilead Sciences, Inc; MSD; Pfizer; Roche; UCB, Grace C. Wright Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Exagen, Eli Lilly, Myriad Autoimmune, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Sanofi Genzyme, UCB, Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Exagen, Eli Lilly, Myriad Autoimmune, Novartis, Regeneron Pharmaceuticals, Inc., Sanofi Genzyme, UCB, Tsutomu Takeuchi Grant/research support from: Eisai Co., Ltd, Astellas Pharma Inc., AbbVie GK, Asahi Kasei Pharma Corporation, Nippon Kayaku Co., Ltd, Takeda Pharmaceutical Company Ltd, UCB Pharma, Shionogi &amp; Co., Ltd., Mitsubishi-Tanabe Pharma Corp., Daiichi Sankyo Co., Ltd., Chugai Pharmaceutical Co. Ltd., Consultant of: Chugai Pharmaceutical Co Ltd, Astellas Pharma Inc., Eli Lilly Japan KK, Speakers bureau: AbbVie GK, Eisai Co., Ltd, Mitsubishi-Tanabe Pharma Corporation, Chugai Pharmaceutical Co Ltd, Bristol-Myers Squibb Company, AYUMI Pharmaceutical Corp., Eisai Co., Ltd, Daiichi Sankyo Co., Ltd., Gilead Sciences, Inc., Novartis Pharma K.K., Pfizer Japan Inc., Sanofi K.K., Dainippon Sumitomo Co., Ltd., Kenneth Kalunian Grant/research support from: Pfizer, Lupus Research Alliance, Sanford Consortium, Consultant of: Genentech, Nektar, BMS, Janssen, AstraZeneca, Biogen, Vielabio, Equillium, Eli Lilly, ILTOO, Abbvie, Amgen, Roche, Gilead, Alena Pechonkina Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Ying Guo Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Shangbang Rao Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., YingMeei Tan Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Robin Besuyen Shareholder of: Galapagos, Employee of: Galapagos, Mark C. Genovese Grant/research support from: Abbvie, Eli Lilly and Company, EMD Merck Serono, Galapagos, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, Pfizer Inc., RPharm, Sanofi Genzyme, Consultant of: Abbvie, Eli Lilly and Company, EMD Merck Serono, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, RPharm, Sanofi Genzyme