THU0188 EFFICACY OF FILGOTINIB IN PATIENTS WITH RHEUMATOID ARTHRITIS WITH POOR PROGNOSTIC FACTORS: POST HOC ANALYSIS OF FINCH 3

Abstract

Background:Patients (pts) with rheumatoid arthritis (RA) with poor prognostic factors (PPF) are at risk for RA progression if disease activity is not rapidly controlled. In FINCH 3 (NCT02886728), filgotinib (FIL)—an oral, potent, selective JAK1 inhibitor—was effective relative to methotrexate monotherapy (MTX mono) in MTX-naïve patients with ≥1 PPF—erosions, seropositivity for rheumatoid factor (RF) or anti-cyclic citrullinated peptide (CCP), or hsCRP ≥4 mg/L.1Objectives:This post hoc analysis examined FIL efficacy in FINCH 3 pts with multiple PPF.Methods:The global, phase 3, double-blind, active-controlled FINCH 3 study randomised MTX-naïve pts with moderately to severely active RA 2:1:1:2 to oral FIL 200 mg once daily + MTX ≤20 mg weekly, FIL 100 mg + MTX, FIL 200 mg mono, or PBO + MTX up to week (W)52. This subgroup analysis included pts with all 4 of the following PPF at baseline (PPF pts): erosions, seropositivity for RF or anti-CCP, hsCRP ≥4 mg/L, and DAS(28)CRP >5.1. Comparisons were not adjusted for multiplicity.Results:Of 1249 pts randomised and treated in FINCH 3, 510 had all 4 PPF. At baseline, relative to the overall FINCH 3 population, PPF pts had longer mean disease duration (2.4 vs 2.2 years); higher mean hsCRP (27.9 vs 17.5 mg/L), mTSS (17.9 vs 13.3), DAS28(CRP) (6.3 vs 5.7), HAQ-DI (1.76 vs 1.56), CDAI (44.3 vs 39.8), and SDAI (47.1 vs 41.5); and greater frequency of seropositivity for RF (90.6% vs 67.9%), anti-CCP (92.4% vs 68.5%), or both (82.9% vs 59.6%). Efficacy in PPF pts was comparable to data from all FINCH 3 pts (Table, Figures 1–2). PPF pts receiving FIL 200 mg with or without MTX vs MTX mono had higher frequencies of ACR20/50/70 response and greater improvement in HAQ-DI at W24; responses were numerically greater for FIL 200 mg + MTX vs FIL 100 mg + MTX or FIL 200 mg mono (Table) and were evident by W12 (data not shown). Radiographic progression at W24 was lower in PPF pts receiving FIL 200 mg + MTX or FIL 200 mg mono vs MTX mono (Figure 1). Proportions of PPF pts receiving FIL 200 mg with or without MTX who achieved DAS28(CRP) <2.6, CDAI ≤2.8, SDAI ≤3.3, and Boolean remission at W24 (Figure 2) were larger vs pts receiving MTX mono and numerically greater vs pts receiving FIL 100 mg + MTX.Table.Efficacy outcomes in patients with 4 PPF and all FINCH 3 patients at W24FIL 200 mg+ MTXFIL 100 mg+ MTXFIL 200 mg monoMTXmonoPPFAllPPFAllPPFAllPPFAlln1724168520787210166416ACR20, %85.5*81.0***83.580.2*81.678.174.771.4ACR50, %70.3***61.5***58.857.0**59.858.1**48.245.7ACR70, %54.1***43.8***37.640.1***43.7*40.0***28.326.0HAQ-DIa−1.2***−0.94***−1.0*−0.90**−1.0*−0.89*−0.9−0.79aMean change from baseline.*, p <0.05;**, p <0.01;***, p <0.001 vs MTX mono, not adjusted for multiplicity.FIL, filgotinib; mono, monotherapy; MTX, methotrexate; PPF, poor prognostic factors.Conclusion:FIL treatment provided rapid and deep disease control including higher rates of remission and other clinical outcomes, improved physical function, and less radiographic progression compared with MTX alone in MTX-naïve pts with RA with 4 PPF, a population at risk for severe progressive disease. In pts with 4 PPF, W24 remission rates following FIL 200 mg with or without MTX were higher vs MTX mono and numerically higher vs FIL 100 mg + MTX.