0299: Radiographic Change in Patients with Rheumatoid Arthritis and Estimated Baseline Yearly Progression ≥5 or < 5: Post Hoc Analysis of Two Phase 3 Trials of Filgotinib

Yoshiya Tanaka¹, Tatsuya Atsumi², Daniel Aletaha³, Robert Landewé⁴, Beatrix Bartok⁵, Alena Pechonkina⁶, Ling Han⁶, Kahaku Emoto⁷, Shungo Kano⁷, Vijay Rajendran⁸ and Tsutomu Takeuchi⁹, ¹University of Occupational and Environmental Health, Kitakyusyu Fukuoka, Japan, ²Hokkaido University, Sapporo, Japan, ³Medical University Vienna, Wien, Austria, ⁴Amsterdam University Medical Center, Meerssen, Netherlands, ⁵Gilead Sciences, Inc., La Jolla, CA, ⁶Gilead Sciences, Foster City, CA, ⁷Gilead Sciences, K.K., Tokyo, Japan, ⁸Galapagos NV, Gent, Belgium, ⁹Keio University and Saitama Medical University, Tokyo, Japan

Background/Purpose: In some patients (pts) with rheumatoid arthritis (RA), especially those with joint damage early in the disease, first-line methotrexate (MTX) treatment may not suffice to prevent further rapid radiographic progression (RRP).¹ In FINCH 1 (NCT02889796), filgotinib 200 mg (FIL200) and 100 mg (FIL100) reduced change in modified total Sharp score (mTSS) vs placebo (PBO) in pts with RA and inadequate response to MTX (MTX-IR).² In FINCH 3 (NCT02886728), FIL200 and FIL100 reduced change in mTSS vs MTX monotherapy (MTX mono) in MTX-naïve pts.³

This study was conducted to evaluate, via post hoc analysis of 2 trials, filgotinib's effects on radiographic progression vs MTX mono in pts with estimated baseline (BL) yearly progression ≥5 or < 5 mTSS units/year.

Methods: The double-blind 52-week (W) FINCH 1 study randomized MTX-IR pts with moderate–severe active RA to FIL200 or FIL100, subcutaneous adalimumab (ADA) 40 mg, or PBO; at W24, PBO pts were rerandomized blinded to FIL200 or FIL100; all took stable background MTX.² In FINCH 3, MTX-naïve pts were randomized, blinded, to FIL200 + MTX, FIL100 + MTX, FIL200 alone, or MTX mono for up to W52.³ This analysis examined subgroups by estimated BL yearly progression (BL mTSS/duration in years of RA diagnosis), based on ≥5 or < 5 mTSS units/year,⁴ a threshold commonly used to define RRP. We assessed effects of filgotinib vs ADA or PBO in mTSS change from BL (CFB) at W24/W52 (using a mixed model for repeated measures) and percentages with no progression (mTSS change ≤0, ≤0.5, ≤smallest detectable change [SDC], using Fisher's exact test).

Results: At BL, 558/1755 MTX-IR and 787/1249 MTX-naïve pts had BL estimated yearly progression ≥5. Median mTSS in pts with BL yearly progression ≥5 and < 5 was 53.25 vs 5.00 respectively in the MTX-IR trial and 6.00 vs 2.50 in the MTX-naïve trial. At W24, the mTSS CFB in pts with BL yearly progression ≥5 and < 5 was 0.84 and 0.22 in MTX-IR pts taking PBO + MTX, and 0.67 and 0.25 in MTX-naïve pts taking MTX mono. At W52, in pts with BL yearly progression ≥5, FIL200 + MTX reduced mTSS change vs PBO + MTX in the MTX-IR trial and vs MTX mono in the MTX-naïve trial (Figure 1). At W24, among pts with estimated BL yearly progression ≥5, FIL200 + MTX increased odds of no progression (≤0.5 or ≤0) vs PBO + MTX in MTX-IR pts and vs MTX mono in MTX-naïve pts (Table 1).

Conclusion: These data suggest filgotinib's inhibition of radiographic progression was numerically greater than MTX monotherapy in RA pts with high estimated BL yearly progression. In those with a more moderate estimated rate of progression, filgotinib suppressed progression comparably to ADA and/or MTX.

References: 1. Smolen JS et al. Ann Rheum Dis. 2018;77:1566–1572. 2. Combe B et al. Ann Rheum Dis. 2021;80:848–858. 3. Westhovens R et al. Ann Rheum. Dis 2021;80:727–738. 4. Vastesaeger N et al. Rheumatology. 2009;48:1114–1121.  

Figure 1. CFB in mTSS at W24 and W52. W52 results include data from Campaign A (all radiographs through W24) and Campaign B (radiographs through W52 including re-reading of BL and W24 radiographs). ADA, adalimumab; BL, baseline; CFB, change from baseline; FIL100, filgotinib 100 mg; FIL200, filgotinib 200 mg; IR, inadequate response; LS, least squares; mono, monotherapy; mTSS, modified total Sharp score; MTX, methotrexate; PBO, placebo; W, week.

Table 1. Ratio of no radiographic progression at W24. MTX-IR ORs are FIL vs PBO + MTX; MTX-naïve are FIL vs MTX. *Nominal P < .05. †Not applicable. ADA, adalimumab; FIL, filgotinib; IR, inadequate response; mTSS, modified total Sharp score; MTX, methotrexate; OR, odds ratio; SDC, smallest detectable change; W, week.

Disclosures: 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; T. Atsumi, Alexion, Chugai Pharmaceutical, Daiichi Sankyo, Mitsubishi Tanabe Pharma, Otsuka Pharmaceutical, Pfizer, Teijin Pharma, AbbVie, Bristol-Myers Squibb (BMS), Eisai, Eli Lilly Japan, Kyowa Kirin, Novartis, Taiho Pharmaceutical, Takeda Pharmaceutical, UCB Pharma, AstraZeneca, Medical and Biological Laboratories, Boehringer-Ingelheim, Ono Pharmaceutical, Gilead Sciences, Inc., Astellas Pharma; D. Aletaha, Novartis, SoBi, Sanofi, Amgen, Lilly, Merck, Pfizer, Roche, Sandoz, Janssen, AbbVie; R. Landewé, Abbott, Amgen, AstraZeneca, BMS, GSK, Novartis, Merck, Pfizer, Schering-Plough, UCB Pharma; 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.; V. Rajendran, Galapagos; T. Takeuchi, Astellas Pharma, Eli Lilly Japan, Gilead Sciences, AbbVie, Eisai Co., Ltd, Pfizer Japan Inc., Asahi Kasei, Chugai, Daiichi Sankyo, Dainippon Sumitomo Eisai, Mitsubishi-Tanabe, Shionogi, Takeda, UCB Japan, Ayumi Pharmaceutical Corporation, Bristol-Myers Squibb, Novartis, Sanofi.