OBJECTIVES: To evaluate the efficacy and safety of different doses and regimens 
of filgotinib, an oral Janus kinase 1 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 IIb 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, 100 or 200 mg filgotinib, administered once daily or 
twice daily. Primary end point was the percentage of patients achieving a week 
12 American College of Rheumatology (ACR)20 response.
RESULTS: Overall, 594 patients were randomised and treated. At week 12, 
significantly more patients receiving filgotinib 100 mg once daily or 200 mg 
daily (both regimens) achieved an ACR20 response versus placebo. For other key 
end points at week 12 (ACR50, ACR-N, Disease Activity Score based on 28 joints 
and C reactive protein value, Clinical Disease Activity Index, Simplified 
Disease Activity Index and Health Assessment Questionnaire-Disability Index), 
differences in favour of 100  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 end 
points and were associated with an increased haemoglobin concentration. No 
significant differences between once-daily and twice-daily regimens were seen. 
Treatment-emergent adverse event rates were similar in placebo and filgotinib 
groups. Serious infections occurred in one and five 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.
TRIAL REGISTRATION NUMBER: NCT01888874.