POS0704 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

Abstract

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.