Active rheumatoid arthritis (RA) patients whose response to methotrexate (MTX) therapy was insufficient showed improvement when MTX was combined with filgotinib, an investigational JAK–1 inhibitor, according to results of a Phase 2b clinical trial.
The study titled, “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),” was published in the journal Annals of the Rheumatic Diseases.
In RA, the Janus kinase (JAK) receptor JAK–1 was shown to promote disease progress as it mediates signaling of potent pro-inflammatory cytokines, such as interleukin-6 (IL-6). Accordingly, JAK inhibitors may help halt RA progression.
The U.S. Food and Drug Administration approved Xeljanz (tofacitinib citrate), a JAK inhibitor, for use in patients with moderately to severely active RA as a second-line agent after MTX. Several other JAK inhibitors are currently being developed as potential RA therapies. One is filgotinib (BLPG0634/GS-6034), a potent and selective inhibitor of JAK–1 being developed by Galapagos.
In the Phase 2 clinical trial (NCT01888874), called DARWIN1, researchers assessed both the efficacy and safety of different doses and regimens of filgotinib as an add-on therapy to MTX in patients with RA and inadequate response to MTX.
The 24–week trial enrolled patients with moderate–to–severe active RA receiving a stable dose of MTX. Enrolled patients were randomly assigned to receive a placebo or 50, 100, or 200 mg of filgotinib administered once or twice daily. In total, 594 patients entered the study.
The trial’s primary endpoint was the percentage of patients achieving at week 12 an American College of Rheumatology (ACR)20 response, which is an improvement in disease activity of at least 20%.
At week 12, a significant number of patients treated with filgotinib 100 mg once daily (64% of patients), 200 mg once daily (69% of patients), or 100 mg twice daily (79% of patients) achieved an ACR20 response when compared to placebo controls (44% of patients).
Additional secondary endpoints — ACR50, Disease Activity Score based on 28 joints and C reactive protein value, and Clinical Disease Activity Index, among others — also showed differences between all filgotinib groups and the placebo group.
Most importantly, filgotinib’s benefits in patient responses were maintained or improved through week 24.
Treatment-emergent adverse event rates were similar in placebo and filgotinib groups. Serious infections occurred in one patient randomized to placebo and in five patients in the filgotinib groups.
Overall, “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,” the research team concluded.