No abstract

No abstract

Objective The long-term safety and efficacy of filgotinib (from phase 2 studies), with or without methotrexate (MTX), for the treatment of patients with rheumatoid arthritis was assessed in DARWIN 3, a long-term, open-label extension study (NCT02065700). Methods Eligible patients completing the 24-week DARWIN 1 (filgotinib + MTX) and DARWIN 2 (filgotinib monotherapy) studies entered DARWIN 3, where they received filgotinib 200 mg/day, except for 15 men who received filgotinib 100 mg/day. Safety analyses were performed using the safety analysis set and exposure-adjusted incidence rate (EAIR) of treatment-emergent adverse events (TEAEs) was calculated. Efficacy was assessed from baseline in the parent studies. Results Of 790 patients completing the phase 2 parent studies, 739 enrolled in the study. Through April 2019, 59.5% of patients had received ≥4 years of study drug. Mean (SD) exposure to filgotinib was 3.55 (1.57) years in the filgotinib + MTX group and 3.38 (1.59) years in the filgotinib monotherapy group. EAIR per 100 patient years of exposure (PYE) for TEAEs was 24.6 in the filgotinib + MTX group and 25.8 in the filgotinib monotherapy group, and for serious TEAEs, the EAIR was 3.1 and 4.3, respectively. ACR20/50/70 responses among patients remaining in the study could be maintained through 4 years, with 89.3%/69.6%/49.1% of filgotinib + MTX group and 91.8%/69.4%/44.4% of monotherapy group maintaining ACR20/50/70 responses based on observed data. Conclusion Filgotinib was well tolerated with a 4-year safety profile comparable to that of the parent trials, both in patients receiving combination therapy with MTX or as monotherapy.

No 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.