Is filgotinib with background methotrexate an option for patients with rheumatoid arthritis?

This study compared the benefit of two doses of filgotinib (Jyseleca) with adalimumab (Humira) and placebo, in patients with rheumatoid arthritis (RA) treated with methotrexate (MTX; Otrexup). The data showed that filgotinib reduced RA signs, improved physical activity, prevented structural joint damage progression, and was well-tolerated in patients with inadequate responses to MTX.

MTX is typically the first-line therapy for patients with RA. Second-line therapy with tumor necrosis factor-alpha inhibitors (TNFαi) such as adalimumab is given to patients with an inadequate MTX response. These biological disease-modifying anti-rheumatic drugs (bDMARDs) have advanced RA management. However, inadequate long-term responses can sometimes occur. By finding new therapies that perform equally well or better than the standard of care (SOC), it is possible to improve RA management in patients that experience inadequate response to bDMARDs.

Filgotinib is a Janus kinase (JAK) inhibitor. JAK is a protein involved in inflammation. Earlier studies showed improved effectiveness in RA treatment with filgotinib compared to placebo. However, comparisons between filgotinib and adalimumab in patients with RA have not been done. 

This study included 1755 patients, with RA. Patients were randomly assigned to one of 4 groups. Group 1 received 200 mg filgotinib (475 patients). Group 2 received 100 mg filgotinib (480 patients). Group 3 had 325 patients who received 40 mg of adalimumab. Group 4 included 475 patients who were given a placebo. All patients still received background MTX. A 20% improvement in American College of Rheumatology criteria (ACR20) and Disease Activity Score (DAS-28) with C reactive protein (CRP; a marker of inflammation) at week 12 were evaluated.

At week 12, 76.6% of patients in group 1 and 69.8% of group 2 achieved ACR20, compared to 49.9% of patients in group 4. 70.5% of patients in group 3 achieved ACR20 after 12 weeks.

Filgotinib treatment was significantly better than placebo and similar to adalimumab based on changes in DAS-28/CRP scores and quality of life.

The authors suggested that filgotinib with background MTX could be a possible treatment option for RA in patients with inadequate responses to MTX.

The study included patients with moderate to severe RA, so results cannot be generalized to patients with less severe disease. Additional safety data on side effects is needed. This study was funded by Gilead, the manufacturer of filgotinib.