Significant dose-dependent relief of both signs and symptoms was seen where methotrexate alone had failed.
Filgotinib provides significant dose-dependent relief of both signs and symptoms of rheumatoid arthritis in patients for whom methotrexate monotherapy has not succeeded.
Oral filgotinib was safe at all doses tested, with a rate of treatment-emergent adverse events similar to that of placebo.
Because only 50% of patients with rheumatoid arthritis respond adequately to methotrexate monotherapy, discovery of safe and effective rescue therapies is important.
As oral medications, janus kinase inhibitors are easy to take, and they work by a mechanism different from that of the primary disease-modifying antirheumatic drug, methotrexate.
Only one janus kinase inhibitor has been FDA approved for use as a second-line alternative to methotrexate when first-line therapy does not control the symptoms of rheumatoid arthritis.
Dr. Kavanaugh and colleagues at the University of California San Diego presented the findings of the DARWIN 2 study in a recent Annals of the Rheumatic Diseases article.
DARWIN 2, a 24-week, multicenter, randomized, double-blind, phase IIb, dose-finding study, looked at filgotinib as monotherapy for patients with rheumatoid arthritis for whom methotrexate failed as a first-line treatment.
Ultimately, 283 adults were included and randomized, all having received a diagnosis of rheumatoid arthritis based on the 2010 American College of Rheumatology/European League Against Rheumatism criteria and all having had unsuccessful methotrexate monotherapy.
Treatment groups received filgotinib doses of 50 mg, 100 mg, and 200 mg and were compared with a control group with regard to efficacy and safety.
The primary outcome was achieving an American College of Rheumatology (ACR) 20 response; secondary end points were achievement of an ACR 50 or 70 response.
At 12 weeks, significantly more patients who received filgotinib had an ACR 20 response across all doses (50 mg, 67%; 100 mg, 66%; 200 mg, 73%) when compared with placebo (29%) (p<0.0001).
At week 12, a statistically significant number of patients who received filgotinib achieved ACR 50 responses when compared with placebo (p<0.05). Those in the 100 mg and 200 mg arms achieved ACR 70 scores with greater frequency.
No difference in the rates of treatment-emergent adverse events were seen between all treatment groups and the placebo group; 26 subjects discontinued treatment (9.2%), which was insignificant when compared with placebo.
Dose-dependent increases in serum creatinine (up to 3.5 Î¼mol/L) were seen in the filgotinib treatment arms; levels plateaued and remained stable until the 24th week. Liver function tests and lipase levels remained stable.
Mean hemoglobin levels increased and neutrophil counts dropped in the filgotinib groups when compared with placebo subjects.
Implications for physicians
• Once-daily oral administration of the janus kinase 1 inhibitor filgotinib is efficacious at 50 mg, 100 mg, and 200 mg with quicker responses in the higher dose ranges in patients with rheumatoid arthritis for whom methotrexate monotherapy has failed.
• Filgotinib doses of 100 mg and 200 mg led to higher rates of ACR 50 and 70 responses, respectively, over 50 mg and placebo doses.
• All doses of filgotinib were well tolerated, with adverse event occurrences similar to those with placebo and only minor effects on laboratory values and hematologic counts.
Galopagos NV provided funding for this research.
A Kavanaugh, J Kremer, L Ponce, et al. “Filgotinib (GLPG0634/GS-6034), an oral selective JAK1 inhibitor, is effective as monotherapy in patients with active rheumatoid arthritis: results from a randomised, dose-finding study (DARWIN 2).” Ann Rheum Dis. 2017;76:1009-1019. doi:10.1136/annrheumdis-2016-210105