In patients with active rheumatoid arthritis (RA) with limited or no prior methotrexate (MTX) exposure, a combination of filgotinib and MTX significantly improves signs and symptoms and physical function; however, filgotinib monotherapy is not superior to MTX monotherapy in achieving a 20% improvement in American College of Rheumatology criteria (ACR20), according to study results published in Annals of the Rheumatic Diseases.
Previous studies have reported that treatment with small-molecule Janus kinase (JAK) inhibitors, including baricitinib, upadacitinib, and tofacitinib, can significantly improve clinical signs and symptoms of RA and radiographic progression in patients with no prior MTX exposure. However, the safety profile and risk for adverse events should be considered.
The objective of the current study was to determine the efficacy and safety of JAK-1 inhibitor filgotinib in patients with active RA with limited or no prior MTX exposure.
The 52-week, multicenter, double-blind, phase 3 study (FINCH 3; ClinicalTrials.gov Identifier: NCT02886728) included 1252 patients with RA (mean age, 53 years, 77% women) who were randomly assigned to receive 2:1:1:2 filgotinib 200 mg with MTX (n=416), filgotinib 100 mg with MTX (n=207), filgotinib 200 mg monotherapy (n=210), or MTX monotherapy (n=416), respectively.
The primary study outcome was percentage of patients achieving ACR20 at week 24.
At week 24, compared with 71% of patients who received MTX only, 81% who received filgotinib 200 mg with MTX and 80% who received filgotinib 100 mg with MTX achieved an ACR20 response (P <.001 and P =.017, respectively). A total of 78% of patients who received filgotinib 200 mg monotherapy achieved an ACR20 response, which was not significantly different from those who received MTX monotherapy (71%; P =.058).
Researchers noted a significant improvement in Health Assessment Questionnaire Disability Index (HAQ-DI) at week 24; the least-squares mean of the treatment difference in change in HAQ-DI from baseline vs MTX was -0.20 (95% CI, -0.27 to -0.12; P <.001) and -0.13 (95% CI, -0.23 to -0.03; P =.008) for filgotinib 200 mg with MTX and filgotinib 100 mg with MTX, respectively.
The percentage of patients who achieved 28-joint Disease Activity Score with C-reactive protein less than 2.6 was significantly higher for patients who received filgotinib 200 mg with MTX (54%) and filgotinib 100 mg with MTX (43%), compared with patients who received MTX monotherapy (29%; P <.001 for both) at week 24.
Overall, both filgotinib doses were well tolerated with an acceptable safety profile. Adverse event rates through week 52 were comparable between all treatments.
The study had several limitations, including the inability to adjust for MTX dose due to the study design, lack of a placebo group, and low progression rate of structural damage that compromised the ability to demonstrate a benefit between the filgotinib arms compared to MTX.
“Filgotinib in combination with MTX could be considered as a treatment option for patients with moderately or severely active [RA] who have limited or no previous exposure to MTX,” the researchers concluded.
Disclosure: This clinical trial was supported by Gilead Sciences. Please see the original reference for a full list of authors’ disclosures.
Westhovens R, Rigby WFC, van der Heijde D, et al. Filgotinib in combination with methotrexate or as monotherapy versus methotrexate monotherapy in patients with active rheumatoid arthritis and limited or no prior exposure to methotrexate: the phase 3, randomised controlled FINCH 3 trial. Ann Rheum Dis. Published online January 15, 2021. doi:10.1136/annrheumdis-2020-219213