CLINICAL OUTCOMES OF METHOTREXATE (MTX)-NAIVE RHEUMATOID ARTHRITIS (RA) PATIENTS (PTS) ON FILGOTINIB (FIL) LONG-TERM EXTENSION (LTE) TRIAL INITIALLY ON FIL OR MTX DURING THE PHASE 3 PARENT STUDY (PS)

BackgroundThe preferential Janus kinase-1 inhibitor FIL is approved for treatment of moderate to severe active RA in Europe and Japan.ObjectivesIn this post hoc, exploratory analysis, efficacy and safety of long-term treatment with FIL (± MTX) were assessed in MTX-naïve pts treated with FIL or MTX in the Phase 3 PS (NCT02886728).1MethodsPts received FIL 200 mg (FIL200)+MTX, FIL 100 mg (FIL100)+MTX, FIL200 alone, or MTX alone up to 52 W in PS.1 Those completing PS on study drug could enter LTE (NCT03025308; data cutoff: June 1, 2020). MTX completers were rerandomized, blinded, to FIL200 or FIL100; pts on FIL in PS remained on the same dose in LTE. MTX was washed out for 4 W at LTE baseline (BL); pts could (re)start MTX and/or other conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) ≥4 W after LTE first dosing.1 Efficacy data to LTE W48 and safety data are reported.ResultsAs of June 1, 2020, 439/492 (89%) and 144/169 (85%) pts who entered LTE from PS FIL200 and PS FIL100 groups, respectively, remained on LTE study treatment; of those rerandomized from MTX, 131/148 (89%) FIL200 and 133/151 (88%) FIL100 pts remained on study treatment. LTE BL characteristics were similar between FIL200 and FIL100 groups. After MTX washout, 17% of FIL200 and 23% of FIL100 pts (re)started MTX (at clinical judgment). ACR20/50/70 response rates among pts from PS FIL arms decreased modestly from LTE BL to W12 then stabilized. Among pts who switched from PS MTX to LTE FIL, response rates remained stable or improved to approach those of PS FIL pts by W48 (Figure 1). Similar trends were seen in DAS28(CRP) and CDAI. Treatment-emergent adverse events (TEAEs), Grade ≥3 AEs, serious AEs, and infections were largely comparable across groups and did not increase after MTX to FIL switch. There were 6 deaths, all among PS FIL200 pts (Table 1).Table 1.EAIRs of TEAEs through June 2020EAIR (95% CI)FIL200+MTX →FIL200 →FIL100+MTX →MTX →MTX →FIL200 LTEFIL200 LTEFIL100 LTEFIL200 LTEFIL100 LTEn=325n=167n=169n=148n=151PYE=474.4PYE=232.5PYE=236.4PYE=213.4PYE=215.4TEAE49.7 (43.8, 56.5)46.9 (38.9, 56.6)49.9 (41.7, 59.8)50.6 (41.9, 61.1)46.4 (38.2, 56.5)TEAE Grade ≥37.2 (5.1, 10.0)6.5 (3.9, 10.7)10.2 (6.8, 15.1)7.0 (4.2, 11.7)7.0 (4.2, 11.6)TE serious AE5.9 (4.1, 8.5)6.0 (3.6, 10.2)8.9 (5.8, 13.6)6.6 (3.9, 11.1)6.5 (3.9, 11.0)Death1.1 (0.3, 2.5)0.4 (0.1, 3.1)0 (0, 1.6)0 (0, 1.7)0 (0, 1.7)Infections28.5 (24.0, 33.7)29.7 (23.4, 37.6)27.5 (21.6, 35.1)28.6 (22.2, 36.7)27.4 (21.2, 35.4)Serious infections1.1 (0.4, 2.5)3.0 (1.4, 6.3)2.5 (1.1, 5.7)1.9 (0.7, 5.0)1.9 (0.7, 4.9)Opportunistic infections0.2 (0, 1.5)0 (0, 1.6)0.8 (0.2, 3.4)0 (0, 1.7)0 (0, 1.7)Herpes zoster0.8 (0.3, 2.2)1.7 (0.6, 4.6)0.8 (0.2, 3.4)1.9 (0.7, 5.0)0.9 (0.2, 3.7)MACE (adjudicated)0.6 (0.1, 1.8)0.9 (0.2, 3.4)0 (0, 1.6)0 (0, 1.7)0 (0, 1.7)VTE (adjudicated for DVT/PE)0.2 (0, 1.2)0.4 (0.1, 3.1)0 (0, 1.6)0 (0, 1.7)0 (0, 1.7)Malignancies (excluding NMSC)0.6 (0.2, 2.0)0 (0, 1.6)1.7 (0.6, 4.5)0.5 (0, 2.6)0 (0, 1.7)NMSC0.6 (0.2, 2.0)0.4 (0.1, 3.1)0.8 (0.2, 3.4)0.5 (0, 2.6)0 (0, 1.7)DVT, deep vein thrombosis; EAIRs, exposure-adjusted incidence rates (per 100 patient-years of exposure); MACE, major adverse cardiovascular event; NMSC, nonmelanoma skin cancer; PE, pulmonary embolism; VTE, venous thromboembolismFigure 1.ConclusionOverall, response rates improved from LTE BL to W48 for pts switched from PS MTX to FIL and decreased modestly for PS FIL pts. Rates of AEs of special interest were generally low and tended to be higher in pts maintained on FIL from PS. Safety findings in this subpopulation were comparable with the PS through W521 and with a 7-trial integrated safety analysis.2 Limitations: the LTE was not formally randomized at BL, the groups were of unequal size, and the switch from MTX to FIL for LTE was by design rather than based on disease activity.References[1]Westhovens R et al. Ann Rheum Dis 2021;80:727–38.[2]Winthrop K et al. Arthritis Rheumatol 2020;72(suppl 10): abstract 0229.AcknowledgementsFunding for the trials was provided by Galapagos NV and Gilead Sciences, Inc. The sponsors participated in the planning, execution, and interpretation of the research. This study was funded by Gilead Sciences, Inc., Foster City, CA. Medical writing support was provided by Gregory Bezkorovainy, MA, of AlphaScientia, LLC, San Francisco, CA; and funded by Gilead Sciences, Inc., Foster City, CA. Funding for this analysis was provided by Gilead Sciences, Inc.Disclosure of InterestsDaniel Aletaha Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Medac, Merck, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Sandoz, Sanofi/Genzyme, and UCB, Consultant of: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Medac, Merck, Novartis, Pfizer, Roche, Sandoz, and Sanofi/Genzyme, Grant/research support from: AbbVie, Merck Sharp & Dohme, Novartis, and Roche, Rene Westhovens Consultant of: Celltrion, Galapagos, and Gilead Sciences, Inc., Grant/research support from: Celltrion, Galapagos, and Gilead Sciences, Inc., Tatsuya Atsumi Speakers bureau: AbbVie Inc., Astellas Pharma Inc., Bristol Myers Squibb Co., Chugai Pharmaceutical Co., Ltd, Daiichi Sankyo Co., Ltd, Eisai Co. Ltd, Eli Lilly Japan K.K., Mitsubishi Tanabe Pharma Co., Otsuka Pharmaceutical Co., Ltd, Pfizer Inc., Takeda Pharmaceutical Co., Ltd, UCB Japan Co. Ltd, Consultant of: AbbVie Inc., Chugai Pharmaceutical Co., Ltd, Daiichi Sankyo Co., Ltd, Eli Lilly Japan K.K., Gilead Sciences, Inc., Pfizer Inc., UCB Japan Co. Ltd, Grant/research support from: AbbVie Inc., Alexion Pharmaceuticals, Inc., Astellas Pharma Inc., Bristol Myers Squibb Co., Chugai Pharmaceutical Co., Ltd, Daiichi Sankyo Co., Ltd, Eli Lilly Japan K.K., Mitsubishi Tanabe Pharma Co., Pfizer Inc., YingMeei Tan Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Alena Pechonkina Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Qi Gong Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Vijay Rajendran Shareholder of: Galapagos NV, Employee of: Galapagos NV, Sander Strengholt Shareholder of: Galapagos BV, Employee of: Galapagos BV, Gerd Rüdiger Burmester Speakers bureau: AbbVie, Eli Lilly, Gilead Sciences, Inc. and Pfizer, Consultant of: AbbVie, Eli Lilly, Gilead Sciences, Inc. and Pfizer