Filgotinib (GLPG0634/GS-6034), an oral JAK1 selective inhibitor, is effective in combination with methotrexate (MTX) in patients with active rheumatoid arthritis and insufficient response to MTX: results from a randomised, dose-finding study

Objectives: To evaluate the efficacy and safety of different doses and regimens of filgotinib, an oral JAK1 inhibitor, as add-on treatment to methotrexate (MTX) in patients with active rheumatoid arthritis (RA) and inadequate response to MTX. Methods: In this 24-week phase 2b study, patients with moderate-to-severe active RA receiving a stable dose of MTX were randomised (1:1:1:1:1:1:1) to receive placebo or 50 mg, 100 mg or 200 mg filgotinib, administered q.d. or b.i.d. Primary endpoint was the percentage of patients achieving a Week 12 ACR20 response. Results: Overall, 594 patients were randomised and treated. At Week 12 significantly more patients receiving filgotinib 100 mg q.d. or 200 mg daily (both regimens) achieved an ACR20 response versus placebo. For other key endpoints at Week 12 (ACR50, ACR-N, DAS28[CRP], CDAI, SDAI and HAQ-DI), differences in favour of 100 mg or 200 mg filgotinib daily were seen versus placebo; responses were maintained or improved through to Week 24. Rapid onset of action and dose-dependent responses were observed for most efficacy endpoints and were associated with an increased haemoglobin concentration. No significant differences between q.d. and b.i.d. regimens were seen. TEAE event rates were similar in placebo and filgotinib groups. Serious infections occurred in 1 and 5 patients in the placebo and filgotinib groups, respectively. No tuberculosis or opportunistic infections were reported. Conclusions: Filgotinib as add-on to MTX improved the signs and symptoms of active RA over 24 weeks, and was associated with a rapid onset of action. Filgotinib was generally well tolerated.