Benefit of Filgotinib, a JAK1 Preferential Inhibitor, in Rheumatoid Arthritis Patients with Previous Rapid Radiographic Progression: Post Hoc Analysis of Two Trials

Abstract

Introduction: We conducted a post hoc analysis of efficacy and safety of filgotinib stratified by estimated radiographic progression rate before baseline (BL) in patients with rheumatoid arthritis (RA) who had inadequate response to methotrexate (MTX; FINCH 1; NCT02889796) or were naïve to it (FINCH 3; NCT02886728).

Methods: Radiographic progression rate was BL-Modified Total Sharp Score (mTSS) divided by RA duration (BL mTSS/year); estimated rapid radiographic progression (e-RRP) was BL change in mTSS/year ≥ 5; and estimated nonrapid radiographic progression (e-NRRP) was BL mTSS/year < 5. Efficacy and safety were compared between subgroups. All p-values are nominal.

Results: In FINCH 1 and FINCH 3, 558/1755 (31.8%) and 787/1249 (63.0%) patients, respectively, had BL e-RRP. BL characteristics were generally similar between subgroups within each trial. At week (W) 24, in FINCH 1, proportions achieving a Disease Activity Score 28 for rheumatoid arthritis with C-reactive protein < 2.6 were significantly greater with filgotinib 200 (FIL200) and 100 mg (FIL100) versus placebo among e-RRP and e-NRRP subgroups. In each study, proportions of FIL-treated patients achieving Clinical Disease Activity Index ≤ 2.8 and Simple Disease Activity Index ≤ 3.3 were similar between subgroups. In FINCH 3, disease activity measures were at least numerically improved among patients receiving FIL versus MTX monotherapy. At W24, mTSS changes from BL (CFB) were greater among patients with e-RRP in FINCH 1 and FINCH 3 versus e-NRRP (0.81 versus 0.19, p = 0.001; 0.67 versus 0.25, p = 0.31, respectively). At W52, in FINCH 1, mTSS CFBs were smaller among e-RRP patients treated with FIL200 (0.40; p < 0.001) and FIL100 (0.77; p = 0.024) versus adalimumab (ADA; 1.46). In FINCH 3 at W52, mTSS CFBs were significantly smaller with FIL200 versus MTX among e-RRP patients. Rates of treatment-emergent adverse events (AEs) were comparable between subgroups and across treatment arms.

Conclusions: Patients with previous e-RRP who received standard care tended to progress radiographically. FIL200 demonstrated persistent, consistent benefit for disease activity control among e-RRP and e-NRRP subgroups, and AE profiles were similar between subgroups. Although filgotinib efficacy was somewhat reduced among patients with e-RRP, filgotinib treatment slowed radiographic progression in both subgroups.

Trial registration: Clinicaltrials.gov NCT02889796, NCT02886728.

Keywords: Adalimumab; Filgotinib; Methotrexate; Rheumatoid arthritis.

© 2022. The Author(s).

Figures

Fig. 1

DAS28(CRP) p-Values are nominal versus PBO or MTX. BL baseline, CDAI Clinical Disease Activity Index, DAS28(CRP) Disease Activity Score in 28 joints with C-reactive protein, e-NRRP estimated nonrapid radiographic progression, e-RRP estimated rapid radiographic progression, FIL filgotinib, MTX methotrexate, SDAI Simplified Disease Activity Index

Fig. 2

mTSS change from baseline at weeks 24 and 52 in e-RRP/e-NRRP subgroups. A FINCH 1 (MTX-IR). B FINCH 3 (MTX-naïve). All p-values are nominal versus PBO or ADA at W24 and versus ADA at W52 in FINCH 1 and versus MTX mono in FINCH 3. ADA at W24 is out of scope for statistical calculation. ADA adalimumab, BL baseline, CFB change from baseline, e-NRRP estimated nonrapid radiographic progression, e-RRP estimated rapid radiographic progression, 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

Fig. 3

Ratio of no radiographic progression in e-RRP and e-NRRP subgroups. A Ratio of no radiographic progression in FINCH 1 (MTX-IR). B Ratio of no radiographic progression in FINCH 3 (MTX-naïve). Full analysis set includes subjects who were randomized and received ≥ 1 dose of study drug. The Fisher’s exact test was used for comparisons between treatment groups. Observed case: only observed values were used for analysis. No missing data imputation was performed. Odds ratio was calculated using 2 × 2 table and the 95% exact confidence limits were provided. *Nominal p < 0.05. For FINCH 1 (MTX-IR), Week 24 ORs are FIL versus PBO + MTX; Week 52 ORs are FIL versus ADA + MTX. For FINCH 3 (MTX-naïve), Week 24 and 52 ORs are FIL versus MTX. ADA adalimumab, e-NRRP estimated nonrapid radiographic progression, e-RRP estimated rapid radiographic progression, MTX methotrexate, OR odds ratio, PBO placebo, RRP rapid radiographic progression

Fig. 4

Cumulative percentile of mTSS change from baseline, and proportions without radiographic progression, at W24 and W52 by e-RRP/e-NRRP subgroup in A FINCH 1 (MTX-IR) and B FINCH 3 (MTX-naïve). Cumulative probability plot of mTSS change from BL at W24 and W52 of each treatment arm for e-RRP and e-NRRP subgroups. CFB in mTSS was analyzed using an analysis of covariance model in which actual scores were converted to rank scores, using the treatment group as a factor and BL rank score as a covariate. Rate of mTSS nonprogression (mTSS CFB ≤ 0.5) was compared using Fisher’s exact test. ADA adalimumab, BL baseline, CFB change from BL, e-NRRP estimated nonrapid radiographic progression, e-RRP estimated rapid radiographic progression, FIL100 filgotinib 100 mg, FIL200 filgotinib 200 mg, IR inadequate response, mono monotherapy, mTSS Modified Total Sharp Score, MTX methotrexate, PBO placebo, W week