Delhi: Study on Filgotinib and Methotrexate in Rheumatoid Arthritis

A combination of filgotinib (FIL) and methotrexate (MTX) significantly improved signs and symptoms and physical function in active rheumatoid arthritis patients irrespective of prior or no MTX exposure, finds a recent study in the journal Annals of the Rheumatic Diseases. However, filgotinib monotherapy did not have a superior ACR20 response rate compared to MTX monotherapy.

Previous studies found treatment with small-molecule Janus kinase (JAK) inhibitors, including upadacitinib, baricitinib, and tofacitinib to be associated with significant improvement in 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.

René Westhovens, University Hospitals KU Leuven, Leuven, Flanders, Belgium, and colleagues aimed to investigate the safety and efficacy of the Janus kinase-1 inhibitor filgotinib in patients with active RA with limited or no prior MTX exposure.

For the purpose, the researchers conducted a 52-week, phase 3, multicentre, double-blind clinical trial. The researchers evaluated once-daily oral filgotinib in 1252 RA patients. They were randomized in the ratio of 2:1:1:2 to filgotinib 200 mg with MTX (FIL200 +MTX), filgotinib 100 mg with MTX (FIL100 +MTX), filgotinib 200 mg monotherapy (FIL200), or MTX.

The primary endpoint was proportion achieving 20% improvement in American College of Rheumatology criteria (ACR20) at week 24.

Key Findings of the Study

• The primary endpoint was achieved by 81% of patients receiving FIL200+ MTX versus 71% receiving MTX.
• A significantly greater proportion treated with FIL100+ MTX compared with MTX achieved an ACR20 response (80%) at week 24.
• Significant improvement in Health Assessment Questionnaire-Disability Index was seen at week 24; least-squares mean change from baseline was −1.0 and −0.94 with FIL200+MTX and FIL100+MTX, respectively, versus −0.81 with MTX.
• Significantly higher proportions receiving FIL200+MTX (54%) and FIL100+MTX (43%) achieved DAS28(CRP) <2.6 versus MTX (29%) at week 24.
• Hierarchical testing stopped for comparison of ACR20 for FIL200 monotherapy (78%) versus MTX (71%) at week 24.
• Adverse event rates through week 52 were comparable between all treatments.

"Our findings show that FIL200+MTX and FIL100+MTX both significantly improved signs and symptoms and physical function in patients with active RA and limited or no prior MTX exposure; FIL200 monotherapy did not have a superior ACR20 response rate versus MTX. Filgotinib was well tolerated, with acceptable safety compared with MTX," wrote the authors.

The study titled, "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," is published in the journal Annals of the Rheumatic Diseases.

DOI: https://ard.bmj.com/content/early/2021/01/14/annrheumdis-2020-219213