Efficacy and Safety of Filgotinib in Patients with High Risk of Poor Prognosis Who Showed Inadequate Response to MTX: A Post Hoc Analysis of the FINCH 1 Study

Abstract

Introduction: This exploratory analysis of FINCH 1 (NCT02889796) examined filgotinib (FIL) efficacy and safety in a subgroup of patients with rheumatoid arthritis (RA) and inadequate response to methotrexate (MTX; MTX-IR) who had four poor prognostic factors (PPFs).

Methods: Patients with MTX-IR received placebo up to week (W)24 or FIL200 mg, FIL100 mg, or adalimumab up to W52; all received MTX. Efficacy and safety data were stratified by four PPFs versus fewer than four PPFs: seropositivity, high-sensitivity C-reactive protein (CRP) ≥ 6 mg/L, Disease Activity Score in 28 joints with CRP > 5.1, and erosions on X-rays.

Results: At baseline, 687/1755 patients had four PPFs. At W12, whether with four PPFs or fewer than four PPFs, response rates on all American College of Rheumatology (ACR) measures were significantly greater with FIL200 and FIL100 versus placebo. At W52, FIL200 ACR20/50/70 response rates remained at least numerically higher versus adalimumab in both subgroups. At W52, FIL200 reduced modified total Sharp score (mTSS) change versus adalimumab in patients with four or fewer than four PPFs.

Conclusions: In high-risk (four PPFs) patients with MTX-IR RA, FIL200 and FIL100 showed similar reductions in disease activity versus placebo at W12 as in patients with fewer than four PPFs. mTSS in patients receiving FIL200 changed little from W24 to W52, while that in patients receiving FIL100 progressed comparably to patients who received adalimumab. Tolerability was comparable across treatment arms and subgroups.

Keywords: Adalimumab; Filgotinib; Methotrexate; Poor prognostic factors.

Fig. 1

Proportions (%) of patients with four and fewer than four PPFs achieving ACR20/50/70 response over time for A ACR20 B ACR50 C ACR70. All treatment groups also received methotrexate. For ACR20, response rates with FIL200 and FIL100 were significantly different (P < 0.05) versus PBO at weeks 2–24, except for FIL100 at week 14, in the four-PPF subgroup and at every timepoint in the fewer-than-four-PPF subgroup. Response rates with FIL200 were significantly different (P < 0.05) versus ADA at weeks 30, 44, and 52 among patients with four PPFs, while FIL100 was not significantly different from ADA at any timepoint. Among patients with fewer than four PPFs, response rates among both filgotinib groups were similar to those of ADA. For ACR50, response rates with FIL200 and FIL100 were significantly different (P < 0.05) versus PBO at every timepoint in the four-PPF subgroup and in the fewer-than-four-PPF subgroup. For ACR70, response rates with FIL200 were significantly different (P < 0.05) versus PBO at every timepoint in both subgroups except at week 2 among patients with four PPFs. FIL100 was significantly different from PBO at every timepoint except weeks 2 and 4 in both subgroups. Response rates with FIL were not significantly different versus ADA at weeks 26–52 in either subgroup. ACR20/50/70 American College of Rheumatology 20%, 50%, and 70% improvement; ADA adalimumab; BL baseline; FIL100 filgotinib 100 mg; FIL200 filgotinib 200 mg; PBO placebo; PPF poor prognostic factor

Fig. 2

Number needed to treat for one additional patient to achieve each efficacy endpoint A FIL200 B FIL100. All treatment groups also received methotrexate. Error bars are not shown when the values span zero. ACR20/50/70 American College of Rheumatology 20%, 50%, and 70% improvement, CDAI Clinical Disease Activity Index, CI confidence interval, DAS28(CRP) Disease Activity Score for rheumatoid arthritis in 28 joints with C-reactive protein, FIL100 filgotinib 100 mg, FIL200 filgotinib 200 mg, MTX methotrexate, PPF poor prognostic factor, NNT number needed to treat, SDAI Simple Disease Activity Index

Fig. 3

CFB in HAQ-DI among patients with four PPFs or others at A W12 and B W52. *P < 0 .05 versus PBO at W12; **P < 0.05 versus ADA at W52. Comparison to ADA at W12 is out of scope for statistical calculation. All treatment groups also received methotrexate. ADA adalimumab, CFB change from baseline, FIL100 filgotinib 100 mg, FIL200 filgotinib 200 mg, HAQ-DI Health Assessment Questionnaire-Disability Index, PBO placebo, PPF poor prognostic factor, W week

Fig. 4

CFB in mTSS among patients with four PPFs or fewer than four PPFs. *P < 0.05 versus PBO at W24 or versus ADA at W52. **P < 0.01 versus PBO at W24 or versus ADA at W52. All treatment groups also received methotrexate. ADA adalimumab, CFB change from baseline, FIL100 filgotinib 100 mg, FIL200 filgotinib 200 mg, mTSS modified total Sharp score, PBO placebo, PPF poor prognostic factor, W week

Fig. 5

LS mean CFB in mTSS among patients with any of the PPFs or four PPFs at A W24 or B W52. Each of the PPF subgroups [sero (+), hsCRP ≥ 6, DAS28(CRP) > 5.1, and erosion > 0] could include patients who also had other PPFs. *P < 0.05 versus PBO at W24; **P < 0.05 versus ADA at W52. Comparison to ADA at W24 is out of scope for statistical calculation. All treatment groups also received methotrexate. ADA adalimumab, CFB change from baseline, DAS28(CRP) disease activity score for rheumatoid arthritis in 28 joints with C-reactive protein, FIL100 filgotinib 100 mg, FIL200 filgotinib 200 mg, hsCRP high-sensitivity C-reactive protein, LS least squares, mTSS modified total Sharp score, PBO placebo, PPF poor prognostic factor, Sero (+) seropositivity for rheumatoid factor or anti-yclic citrullinated peptide, W week