Efficacy and Safety of Filgotinib in Patients with Inadequate Response to Methotrexate, with 4 or < 4 Poor Prognostic Factors: A Post Hoc Analysis of the FINCH 1 Study

BackgroundPatients (pts) with rheumatoid arthritis (RA) and poor prognostic factors1 (PPF) are at risk for progression without adequate treatment. Filgotinib (FIL) is a once daily Janus kinase 1 preferential inhibitor. In FINCH 1 (NCT02889796), FIL 200 mg (FIL200) was effective vs placebo (PBO) and noninferior to adalimumab (ADA) in pts with RA and inadequate response to methotrexate (MTX-IR); FIL200 and FIL 100 mg (FIL100) were well tolerated.2ObjectivesThis post hoc, exploratory analysis examined efficacy and safety of FIL in MTX-IR pts with 4 or <4 PPF.MethodsThe FINCH 1 52-week (W), double-blind trial randomised MTX-IR pts with moderate–severe RA to FIL200 or FIL100, ADA, or PBO; all received background MTX. PBO pts were rerandomised, blinded, at W24 to FIL200 or FIL100. We examined pts with 4 PPF at baseline (BL): erosions on X-ray, seropositivity for rheumatoid factor or anticyclic citrullinated peptide, high-sensitivity C-reactive protein (hsCRP) ≥6 mg/L, and disease activity score in 28 joints with CRP (DAS28[CRP]) >5.1, along with those with <4 PPF. Efficacy included DAS28(CRP) <2.6 and modified Total Sharp Score (mTSS) change from baseline (CFB). Fisher’s exact test was used for DAS28(CRP); the mixed-effects model was used to generate least squares mean mTSS CFB. P values were nominal, not adjusted for multiplicity.ResultsAt BL, of 1755 randomized, treated pts, 687 had 4 PPF, and 1068 had <4 PPF. Among pts with <4PPF, 804 [75%] had erosions, 810 [76%] were seropositive, 377 [35%] had hsCRP ≥6 mg/L, 638 [60%] had DAS28[CRP] >5.1). Pts with 4 vs <4 PPF were aged 53 vs 52 years, had RA duration 8.3 vs 7.4 years, DAS28(CRP) 6.3 vs 5.4, and SDAI 45.6 vs 37.7. In pts with 4 or <4 PPF, higher proportions receiving FIL200 or FIL100 achieved DAS28(CRP) <2.6 at W12 vs PBO (nominal P <.001); proportions with DAS28(CRP) <2.6 increased with FIL200, FIL100, or ADA at W52 (Figure 1). DAS28(CRP) responses for FIL200 at W52 were similar in 4 vs <4 PPF pts; FIL100 and ADA responses were numerically higher in <4 vs 4 PPF pts. At W24, mTSS CFB in pts with 4 PPF was 0.21, 0.23, 0.30, and 0.66 for FIL200, FIL100, ADA, and PBO (P <.05 for FIL200 and FIL100 vs PBO); corresponding changes in <4 PPF pts were 0.08, 0.10, 0.11, and 0.24 (P >.05). At W52, mTSS CFB in 4 PPF pts was 0.29, 0.84, and 0.80 for FIL200, FIL100, and ADA, respectively, and 0.14, 0.25, and 0.53 in <4 PPF pts. Rates of adverse events (AEs), including AEs of interest, were comparable for pts with 4 PPF and <4 PPF for all treatment arms (Table 1).Table 1.AEs and AEs of interest in BL 4 PPF and <4 PPF subgroups4 PPF<4 PPFFIL200FIL100ADAPBO beforeFIL200FIL100ADAPBO(n = 191)(n = 189)(n = 126)W24 switch (n = 181)(n = 284)(n = 291)(n = 199)before W24 switch (n = 294)All AEs146 (76.4)136 (72.0)85 (67.5)90 (49.7)206 (72.5)214 (73.5)154 (77.4)164 (55.8)AEs of interestSerious infectious AE5 (2.6)4 (2.1)6 (4.8)2 (1.1)8 (2.8)9 (3.1)4 (2.0)2 (0.7)Opportunistic infections001 (0.8)0001 (0.5)0Active tuberculosis0000001 (0.5)0Herpes zoster1 (0.5)1 (0.5)1 (0.8)05 (1.8)3 (1.0)1 (0.5)2 (0.7)Hepatitis B or C01 (0.5)001 (0.5)01 (0.5)0MACE01 (0.5)01 (0.6)01 (0.3)1 (0.5)1 (0.3)VTE001 (0.8)1 (0.6)1 (0.4)001 (0.3)DVT001 (0.8)1 (0.6)0001 (0.3)PE00001 (0.4)000Malignancy0003 (1.7)2 (0.7)2 (0.7)2 (1.0)0(non-NMSC)GI perforation00001 (0.4)000Values are n (%). ADA, adalimumab; AE, adverse event; BL, baseline; DVT, deep vein thrombosis; FIL100, filgotinib 100 mg; FIL200; filgotinib 200 mg; GI, gastrointestinal; MACE, major adverse cardiac event; NMSC, nonmelanoma skin cancer; PBO, placebo; PE, pulmonary embolism; PPF, poor prognostic factor; VTE, venous thromboembolism; W, week.ConclusionIn high-risk (4 PPF) pts with MTX-IR RA, FIL200 and FIL100 showed similar reductions in disease activity vs PBO at W12 as in pts with <4 PPF; mTSS in FIL200 pts changed little from W24 to W52. Tolerability was comparable across treatment arms, regardless of presence of 4 or <4 PPF.References[1]Smolen JS et al. Ann Rheum Dis. 2020;79:685–99.[2]Combe B et al. Ann Rheum Dis. 2021;80:848–58.AcknowledgementsThis study was funded by Gilead Sciences, Inc., Foster City, CA. Medical writing support was provided by Rob Coover, MPH, of AlphaScientia, LLC, San Francisco, CA, and was funded by Gilead Sciences, Inc., Foster City, CA. Funding for this analysis was provided by Gilead Sciences, Inc. The sponsors participated in the planning, execution, and interpretation of the research.Disclosure of InterestsBernard Combe Speakers bureau: AbbVie, Bristol-Myers Squibb, Celltrion, Eli Lilly, Gilead-Galapagos, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, and Roche-Chugai, Consultant of: AbbVie, Bristol-Myers Squibb, Celltrion, Eli Lilly, Gilead-Galapagos, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, and Roche-Chugai, Grant/research support from: Pfizer and Roche-Chugai, Yoshiya Tanaka Speakers bureau: AbbVie, Amgen, Astellas, AstraZeneca, Behringer-Ingelheim, Bristol-Myers, Chugai, Eisai, Eli Lilly, Gilead Sciences, Inc., Mitsubishi-Tanabe, and YL Biologics, Paid instructor for: AbbVie, Amgen, Astellas, AstraZeneca, Behringer-Ingelheim, Bristol-Myers, Chugai, Eisai, Eli Lilly, Gilead Sciences, Inc., Mitsubishi-Tanabe, and YL Biologics, Grant/research support from: AbbVie, Asahi-Kasei, Boehringer-Ingelheim, Chugai, Corrona, Daiichi-Sankyo, Eisai, Kowa, Mitsubishi-Tanabe, and Takeda, Maya H Buch Speakers bureau: AbbVie, Eli Lilly, Gilead Sciences, Inc., Merck-Serono, Pfizer, Roche, Sanofi, and UCB, Paid instructor for: AbbVie, Eli Lilly, Gilead Sciences, Inc., Merck-Serono, Pfizer, Roche, Sanofi, and UCB, Consultant of: AbbVie, Eli Lilly, Gilead Sciences, Inc., Merck-Serono, Pfizer, Roche, Sanofi, and UCB, Grant/research support from: AbbVie, Eli Lilly, Gilead Sciences, Inc., Merck-Serono, Pfizer, Roche, Sanofi, and UCB, Gerd Rüdiger Burmester Speakers bureau: AbbVie, Eli Lilly, Pfizer, and Gilead Sciences, Inc., Consultant of: AbbVie, Eli Lilly, Pfizer, and Gilead Sciences, Inc., Beatrix Bartok Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Alena Pechonkina Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Ling Han Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Kahaku Emoto Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences K.K., Shungo Kano Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences K.K., Thijs Hendrikx Employee of: Galapagos BV, Daniel Aletaha Speakers bureau: Bristol-Myers Squibb, Merck Sharp & Dohme, and UCB; AbbVie, Amgen, Celgene, Eli Lilly, Medac, Merck, Novartis, Pfizer, Roche, Sandoz, and Sanofi/Genzyme., Consultant of: AbbVie, Amgen, Celgene, Eli Lilly, Medac, Merck, Novartis, Pfizer, Roche, Sandoz, and Sanofi/Genzyme; Janssen, Grant/research support from: from AbbVie, Merck Sharp & Dohme, Novartis, and Roche