Filgotinib Plus Methotrexate Improves Disease Activity, Functional Measures in MTX-IR RA

In high-risk patients, as defined by having 4 poor prognostic factors (PPFs), with rheumatoid arthritis (RA) and inadequate response to methotrexate (MTX; MTX-IR), filgotinib (FIL) treatment of either 200 mg (FIL200) or 100 mg (FIL100) demonstrated similar reductions in disease activity when compared with patients with RA at a lower risk at week 12. Patients receiving FIL100 also had comparable improvements when compared with patients receiving adalimumab, although modified total Sharp score (mTSS) did not show significant changes in the FIL200 group between week 24 and week 52, according to a study published in Springer.¹ Tolerability was similar across both treatment arms and subgroups.

“Despite the widespread availability of disease-modifying antirheumatic drugs (DMARDs), many patients are not able to achieve and sustain remission of RA,” investigators stated. “Failed or inadequate response to DMARDs is associated with poor prognosis; additionally, several disease characteristics have been identified as PPFs in early RA, including seropositivity defined by rheumatoid factor (RF) or cyclic citrullinated peptide (CCP) positive, high baseline high-sensitivity C-reactive protein (hsCRP), high baseline disease activity, and extant bone erosion at disease onset.”

In the exploratory analysis of the global, phase 3, active-controlled, double-blind FINCH 1 (NCT02889796) study, investigators evaluated the efficacy and safety of FIL in a subgroup of MTX-IR patients with moderate to severe RA and 4 PPFs. Patients, all receiving a weekly background dose of MTX, were given either placebo up to week 24 or FIL200mg, FIL100 mg, or subcutaneous adalimumab (ADA) 40 mg up to week 52. Safety and efficacy of patients with 4 PPFs were compared with those with fewer than 4 PPFs. Data was evaluated using the Disease Activity Score in 28 joints with C-reactive protein (DAS28[CRP]) >5.1, seropositivity, high-sensitivity CRP ≥ 6 mg/L, and erosions on X-rays.

Of the 1755 patients included in the study, 687 (39%) had 4 PPFs. At week 12, response rates across all American College of Rheumatology (ACR) measures were significantly greater with patients receiving FIL100 and FIL200 when compared with placebo, regardless of PPF status. Baseline demographics and clinical characteristics were similar among subgroups. RA duration was 8.3 years in patients with 4 PPFs compared with 7.4 years in those with fewer than 4 PPFs. At week 52, patients receiving FIL200 had numerically higher ACR 20%, 50%, and 70% improvements (ACR20/50/70) when compared with the adalimumab group. The FIL200 cohort also demonstrated a reduced mTSS change when compared with adalimumab in patients with 4 or fewer PPFs at week 52.

Although greater efficacy was associated with patients receiving FIL200 as opposed to FIL100, no safety penalty was reported. Treatment-emergent adverse events did not increase after patients switched from placebo to filgotinib.

The post hoc nature of the study hindered the analysis, as did the unbalanced number of patients with and without 4 PPFs. Further, additional unidentified and unevaluated baseline factors may have contributed to patients’ outcomes and affected treatment outcomes.

“Whether all 4 PPFs or fewer than 4 PPFs were present, FIL200 provided consistent symptom relief, physical function improvement, and suppression of radiographic progression, while the other treatment groups offered mixed results, with more robust effects among patients with fewer than 4 PPFs,” investigators concluded. “Filgotinib may thus represent a beneficial treatment option for patients with RA who have had inadequate response to MTX and have high risk of disease progression and poor prognosis.”

Reference:

Combe BG, Tanaka Y, Buch MH, et al. 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 [published online ahead of print, 2022 Oct 9]. Rheumatol Ther. 2022;10.1007/s40744-022-00498-x. doi:10.1007/s40744-022-00498-x