For patients with rheumatoid arthritis (RA) who have poor prognostic factors associated with rapid disease progression, treatment with methotrexate plus the JAK-1 inhibitor filgotinib was more safe and effective than treatment with methotrexate alone. This is according to findings from a post hoc analysis of the FINCH 3 study published in RMD Open.
Investigators conducted a post hoc analysis of the FINCH 3 study, a phase III, randomized, double-blind, active-controlled study (NCT02886728). Patients enrolled in FINCH 3 were randomly assigned 2:1:1:2 to receive oral filgotinib (FIL) 200 mg once daily plus oral methotrexate (MTX) 20 mg or less once weekly, FIL 100 mg daily plus oral MTX 20 mg or less once weekly, FIL 200 mg monotherapy, and oral MTX monotherapy. Therapy lasted as long as 52 weeks. Investigators included in the study patients with at least 1 of the following: seropositivity for rheumatoid factor (RF) or anticyclic citrullinated peptide (anti-CCP) antibodies, high-sensitivity C-reactive protein (CRP) 4 mg/L or greater, and the presence of at least 1 joint erosion.
Investigators defined poor prognostic factors (PPFs) as seropositivity for RF and/or anti-CCP antibodies, high-sensitivity CRP 4mg/L or greater, high Disease Activity Score (DAS), and the presence of erosions at baseline. They looked at treatment efficacy and safety in all patients who received at least 1 dose of a medication, as well as several patient subgroups.
Of 1,249 patients in FINCH 3, 40.8% had all 4 PPFs at baseline, 77.8% of whom completed treatment through week 52. The mean age was 53 years, and 76.9% were women.
Among the patients with all 4 PPFs, treatment with FIL 200 mg plus MTX was more effective than MTX monotherapy (nominal P <.05), and there was no significant difference in treatment efficacy between FIL 100 mg and FIL 200 mg groups relative to MTX monotherapy. However, compared with the overall cohort, patients with all 4 PPFs achieved a lower disease activity score and all remission measures at similar or higher rates when treated with FIL 200 mg with or without MTX, and at lower rates when treated with FIL 100 mg plus MTX or MTX monotherapy. This was not the case for patients with only 2 or 3 PPFs.
There were improvements in disease activity for patients with all 4 PPFs who received any FIL regimen vs MTX monotherapy at week 12 persisting through week 52 (nominal P <.05 at weeks 12, 24, and 52).
Patients with all 4 PPFs treated with any FIL regimen vs MTX monotherapy were associated with similar or greater improvement in baseline physical function and patient-assessed pain relative to the overall cohort, it was noted. Patient-assessed pain further decreased from baseline at week 24 for all patients treated with FIL, except those treated with FIL 100 mg, relative to MTX monotherapy. Radiographic progression at week 24 decreased in all patients treated with FIL, except those treated with FIL 100 mg, relative to MTX monotherapy. By week 52, all patients treated with FIL had less radiographic progression compared with those treated with MTX monotherapy.
Patients in the overall cohort treated with any FIL regimen achieved low disease activity at weeks 24 and 52 more frequently than those on MTX monotherapy (nominal P <.05). In addition, the proportions of patients achieving a lower disease activity score and remission at week 24 were higher in those treated with any FIL regimen vs MTX monotherapy. These proportions remained higher at week 52 only for patients treated with FIL 200 mg plus MTX vs MTX monotherapy.
Patients with established disease (6 months or longer) had higher remission rates following treatment with FIL 200 mg with or without MTX vs FIL 100 mg plus MTX or MTX monotherapy.
Treatment-emergent adverse events were comparable in the overall cohort vs those with all 4 PPFs, and among treatment arms as well. Exceptions included infections, serious infections, and herpes zoster infections, which were more frequent in patients with all 4 PPFs treated with any FIL regimen compared with the overall cohort receiving the same treatment, or patients with PPFs receiving other treatments. In general, the FIL safety profile was maintained and consistent with the integrated safety analysis.
The study was limited by its post hoc nature, the small number of patients with all 4 PPFs, imbalances among treatment groups, and the fact that it was not powered for subgroup comparisons.
“Given the efficacy of filgotinib 200 mg plus MTX in particular versus MTX monotherapy in [RA patients with multiple PPFs], addition of filgotinib may be a reasonable option for patients with PPFs who have unsatisfactory response to MTX plus glucocorticoids or who relapse on glucocorticoid tapering,” the study authors wrote.
Disclosure: Several study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Aletaha D, Westhovens R, Gaujoux-Viala C, et al. Efficacy and safety of filgotinib in methotrexate-naive patients with rheumatoid arthritis with poor prognostic factors: post hoc analysis of FINCH 3. RMD Open. Published online July 24, 2021. doi:10.1136/rmdopen-2021-001621