0918: 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

BERNARD COMBE¹, Yoshiya Tanaka², Maya Buch³, Gerd Burmester⁴, Beatrix Bartok⁵, Alena Pechonkina⁶, Ling Han⁶, Kahaku Emoto⁷, Shungo Kano⁷, Thijs Hendrikx⁸ and Daniel Aletaha⁹, ¹Montpellier University, Montpellier, France, ²University of Occupational and Environmental Health, Kitakyusyu Fukuoka, Japan, ³University of Manchester and NIHR Manchester Biomedical Research Centre, Manchester, United Kingdom, ⁴Charité University Medicine Berlin, Berlin, Germany, ⁵Gilead Sciences, Inc., La Jolla, CA, ⁶Gilead Sciences, Foster City, CA, ⁷Gilead Sciences, K.K., Tokyo, Japan, ⁸GLPG, Leiden, Netherlands, ⁹Medical University Vienna, Wien, Austria

Background/Purpose: Patients (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.² This post hoc, exploratory analysis examined efficacy and safety of FIL in MTX-IR pts with 4 or < 4 PPF.

Methods: The FINCH 1 52-week (W), double-blind trial randomized MTX-IR pts with moderate–severe RA to FIL200 or FIL100, ADA, or PBO; all received background MTX. PBO pts were rerandomized, 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.

Results: At 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).

Conclusion: In 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.
Figure 1. Proportions with DAS28(CRP) < 2.6 at W12 and W52. P-values are nominal. ADA, adalimumab; DAS28(CRP), Disease Activity Score in 28 joints with C-reactive protein; FIL100, filgotinib 100 mg; FIL200, filgotinib 200 mg; PBO, placebo; PPF, poor prognostic factor; W, week.

Table 1. AEs and AEs of interest in BL 4 PPF and < 4 PPF subgroups. Values 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.
Disclosures: B. COMBE, AbbVie, Bristol Myers Squibb, Celltrion, Galapagos, Gilead, Janssen, Lilly, MSD, Pfizer, Roche-Chugai, Novartis; Y. Tanaka, Lilly, AbbVie, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Pfizer, Mitsubishi Tanabe, GlaxoSmithKline, Asahi Kasei, Takeda, Astellas, Janssen, Novartis, Sanofi, UCB, YL Biologics, MSD, Ono, Taisho Toyama, Celltrion, Gilead, Boehringer-Ingelheim, Corrona, Kowa, Amgen, AstraZeneca, AstraZeneca, Eli Lilly; M. Buch, AbbVie, Galapagos, Gilead, Pfizer, Eli Lilly, Merck-Serono, Roche, UCB; G. Burmester, AbbVie, Galapagos, Lilly, MSD, Pfizer, Roche, UCB, Janssen, Gilead Sciences, Inc.; B. Bartok, Gilead Sciences, Inc.; A. Pechonkina, Gilead Sciences, Inc.; L. Han, Gilead Sciences, Inc.; K. Emoto, Gilead Sciences, K.K.; S. Kano, Gilead Sciences, K.K.; T. Hendrikx, Galapagos BV; D. Aletaha, Novartis, SoBi, Sanofi, Amgen, Lilly, Merck, Pfizer, Roche, Sandoz, Janssen, AbbVie.