Efficacy and Safety of Selective JAK 1 Inhibitor Filgotinib in Active Rheumatoid Arthritis Patients With Inadequate Response to Methotrexate

Summary

The administration of Janus kinase (JAK) inhibitors as well as biological disease-modifying anti-rheumatic drugs has dramatically improved even the clinical outcomes in rheumatoid arthritis (RA) patients with inadequate response to methotrexate (MTX). The dysregulation of JAK-signal transducer and activator of transcription (STAT) pathways via overproduction of cytokines, such as interleukin-6 (IL-6) is involved in the pathogenesis of RA. Filgotinib is a selective JAK1 inhibitor to be approved for use in RA. Filgotinib is effective in suppressing disease activity and preventing the progression of joint destruction due to inhibition of the JAK-STAT pathway. IL-6 inhibitors such as tocilizumab also inhibit the JAK-STAT pathways due to inhibition of IL-6 signaling. We will evaluate whether the effectiveness and safety of filgotinib monotherapy is non-inferior to those of tocilizumab monotherapy in RA patients with inadequate response to MTX.

Timeline

Start

2021-03-03

Primary completion

2023-02-28

Completion

2023-12-31

Publications

• Shimizu T, Kawashiri SY, Koga T, Kiya R, Morita M, Kawasaki R, Kuroda S, Tashiro S, Sato S, Yabe M, Misaki K, Hanai S, Nakagomi D, Ogasawara M, Tamura N, Watanabe R, Kanazawa H, Atsumi T, Ueki Y, Okano T, Suzuki T, Takaoka H, Hamada H, Hidaka T, Furuta S, Hosogaya N, Yamamoto H, Kawakami A. Efficacy and safety of filgotinib versus tocilizumab in active rheumatoid arthritis: A randomized, open-label, multicenter study with clinical and musculoskeletal ultrasound evaluation (TRANSFORM study). Drug Discov Ther. 2026 May 17;20(2):175-189. doi: 10.5582/ddt.2026.01008. Epub 2026 Apr 27.
• Shimizu T, Kawashiri SY, Morimoto S, Kawazoe Y, Kuroda S, Kawasaki R, Ito Y, Kiya R, Sato S, Yamamoto H, Kawakami A. Efficacy and safety of selective JAK 1 inhibitor filgotinib in active rheumatoid arthritis patients with inadequate response to methotrexate: comparative study with filgotinib and tocilizumab examined by clinical index as well as musculoskeletal ultrasound assessment (TRANSFORM study): study protocol for a randomized, open-label, parallel-group, multicenter, and non-inferiority clinical trial. Trials. 2023 Mar 3;24(1):161. doi: 10.1186/s13063-023-07176-5.

Drugs

Indications