POS0664 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

Abstract

BackgroundIn 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.3ObjectivesTo 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.MethodsThe double-blind 52-week (W) FINCH 1 study randomised MTX-IR pts with moderate–severe active RA to FIL200 or FIL100, subcutaneous adalimumab (ADA) 40 mg, or PBO; at W24, PBO pts were rerandomised blinded to FIL200 or FIL100; all took stable background MTX.2 In FINCH 3, MTX-naïve pts were randomised, 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 W24 progression (mTSS change ≤0, ≤0.5, ≤smallest detectable change [SDC], using Fisher’s exact test).ResultsAt 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).Table 1.Ratio of no radiographic progression at W24FINCH 1: MTX-IRFIL200 + MTXFIL100 + MTXADA + MTXPBO + MTXBL yearly progression≥5(n = 138)<5(n = 267)≥5(n = 139)<5(n = 265)≥5(n = 91)<5(n = 180)≥5(n = 101)<5(n = 250)% with no progression (≤0.5)87.797.088.592.587.993.976.291.6OR2.22*2.97*2.40*1.12††††% with no progression (≤0)80.491.881.388.380.289.467.386.4OR2.00*1.752.11*1.19††††% with no progression (≤SDC [1.36])91.398.192.196.692.395.681.294.0OR2.43*3.35*2.70*1.82††††FINCH 3: MTX-naïveFIL200 + MTXFIL100 + MTXFIL200 monoMTXBL yearly progression≥5<5≥5<5≥5<5≥5<5(n = 221)(n = 134)(n = 121)(n = 63)(n = 115)(n = 58)(n = 224)(n = 132)% with no progression (≤0.5)86.994.083.593.789.689.778.687.9OR1.81*2.171.382.032.34*1.20††% with no progression (≤0)78.783.672.784.180.087.967.980.3OR1.75*1.251.261.31.89*1.79††% with no progression (≤SDC [1.53])93.797.891.796.895.796.689.395.5OR1.772.081.331.452.641.33††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.ConclusionThese 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.