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 (DARWIN 1)
In these two Phase 2b studies, filgotinib (a selective JAK-1 inhibitor) was shown to improve the signs and symptoms of RA (compared with placebo), either as monotherapy or when added to MTX.
DARWIN 1 included 594 patients with moderate to severe RA on a stable dose of MTX, while DARWIN 2 included 283 patients who stopped taking MTX before the start of the study. After 12 weeks’ treatment, significantly more patients who were receiving filgotinib 100 mg or
200 mg daily in DARWIN 1 or any filgotinib dose (50-, 100- or 200 mg daily) in DARWIN 2 achieved an ACR20 response compared with placebo. Significant differences in favour of filgotinib 100 mg and 200 mg daily were seen for other key efficacy endpoints. Responses were rapid and were sustained for 24 weeks.
Filgotinib was well tolerated in both studies. More treatment-emergent AEs were considered related to study treatment for filgotinib than placebo. Dose-dependent increases in haemoglobin concentrations and decreases in neutrophil counts were seen, but these tended to stabilise with continued treatment.
These encouraging data support the future development of filgotinib for the treatment of active RA in patients receiving MTX and as monotherapy, in patients who have had an inadequate response to MTX treatment.