P199 Clinical outcomes up to week 48 of ongoing filgotinib rheumatoid arthritis long-term extension trial of biologic disease modifying anti-rheumatic drugs inadequate responders initially on filgotinib or placebo in a Phase 3 trial

Abstract Background/Aims The preferential Janus kinase-1 inhibitor filgotinib (FIL) is approved to treat RA in Europe. We assessed FIL efficacy/safety in patients (pts) with inadequate response (IR) to biologic DMARDs (bDMARDs) in a long-term extension trial (LTE; NCT03025308) enrolled from a Phase 3 parent study (PS; NCT02873936). Methods bDMARD-IR pts received FIL 200mg (FIL200), 100mg (FIL100), or placebo (PBO) and stable conventional synthetic (cs)DMARDs up to 24 weeks (W). At W14 of the PS, pts with IR to FIL or PBO (<20% improvement in swollen and tender joint counts) switched to standard of care (SOC). Pts completing PS on FIL, PBO, or SOC could enter LTE. PS FIL pts were maintained, blinded, on their FIL dose; PS PBO and SOC pts were rerandomized, blinded, to FIL200 or FIL100. We report efficacy up to LTE W48 for ACR20/50/70 improvement, DAS28[CRP] ≤3.2 and <2.6, and CDAI ≤10 and ≤2.8. Exposure-adjusted incidence rates (EAIR)/100 pt-years of exposure of treatment-emergent adverse events (TEAEs) and AEs of special interest (AESIs) are summarized up to data cutoff of June 1, 2020. Results The PS included 147, 153, and 148 pts on FIL200, FIL100, and PBO. Of the FIL200 pts who entered LTE, 80/121 continued study drug at June 1, 2020, as did 76/110 FIL100 pts. Pts still on LTE FIL from PBO were 35/47 FIL200 and 32/46 FIL100 pts; from SOC: 13/23 FIL200 and 13/22 FIL100 pts. LTE baseline (BL) characteristics were similar in FIL200 and FIL100 pts (mean RA duration: 13.2 and 12.8 years, DAS28[CRP]: 3.5 and 3.7). During LTE, PS FIL ACR20/50/70 response rates decreased modestly by W48. Among PS PBO pts, response rates were lower at LTE BL but reached similar levels as PS FIL pts by W48; rates increased up to W48 in SOC/FIL pts (either dose) but not to levels of other groups. Percentages of pts attaining DAS28(CRP) ≤3.2, DAS28(CRP) <2.6, CDAI ≤10, and CDAI ≤2.8 were maintained up to W48 for FIL/FIL pts, while PBO/FIL and SOC/FIL pts showed similar patterns as for ACR responses. TEAE, serious AE, and serious infection EAIRs were higher in SOC/FIL pts vs FIL/FIL or PBO/FIL pts but samples were small, and confidence intervals overlapped. Five pts died: FIL200/FIL200, n = 3; PBO/FIL200, n = 1; FIL100/FIL100, n = 1. There were no opportunistic infections. EAIRs of MACE were low DVT/PE occurred in two FIL200/FIL200, one FIL100/FIL100, and one SOC/FIL200 pts. Conclusion Efficacy was mostly maintained in PS FIL pts up to W48. Response among PS PBO and SOC pts increased from BL to W48, but response in PS SOC pts continued to be lower than in other groups; these pts may represent a refractory population. FIL safety was largely consistent between PS and LTE. Disclosure M. Buch: Honoraria; reports research support, consulting, speaker or personal fees from AbbVie; Eli Lilly and Co.; Gilead Sciences, Inc.; Merck-Serono; Pfizer; Roche; Sanofi; and UCB. Grants/research support; received funding (paid to her host institution) for research from Gilead Gilead Sciences, Inc. T. Takeuchi: Consultancies; serving as a consultant for Astellas, Chugai, and Eli Lilly Japan. Member of speakers’ bureau; Speaker’s bureau AbbVie, AYUMI, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Eli Lilly Japan, Gilead Sciences, Mitsubishi-Tanabe, Novartis, Pfizer Japan, Sanofi, and Dainippon Sumitomo. Grants/research support; reports receiving grant/research support from AbbVie, Asahi Kasei, Astellas, Chugai, Daiichi Sankyo, Eisai, Mitsubishi-Tanabe, Shionogi, Takeda, and UCB Japan. V. Rajendran: Shareholder/stock ownership; employee of and shareholder in Galapagos NV. J. Gottenberg: Consultancies; serving as a consultant for Bristol-Myers Squibb, Sanofi Genzyme, and UCB. Member of speakers’ bureau; serving on a speaker’s bureau for Gilead Sciences, Inc., Galapagos, AbbVie, Eli Lilly and Co., Roche, Sanofi Genzyme, and UCB. Grants/research support; reports receiving grant/research support from Bristol-Myers Squibb and Pfizer. A. Pechonkina: Other; employee of Gilead Sciences, Inc. and may own stock in Gilead Sciences, Inc. Y. Tan: Other; employee of Gilead Sciences, Inc. and may own stock in Gilead Sciences, Inc. Q. Gong: Other; employee of Gilead Sciences, Inc. and may own stock in Gilead Sciences, Inc. K. Van Beneden: Other; employee of and shareholder in Galapagos NV. R. Caporali: Honoraria; reports receiving speaker’s fees and consultation grants from AbbVie, BMS, Celltrion, Fresenius-Kabi, Gilead-Galapagos, Lilly, MSD, Pfizer, Roche, Samsung-Bioepis, Sanofi and UCB.