EQUATOR biomarker analysis supports anti-inflammatory action of filgotinib in PsA
medwireNews: An exploratory biomarker analysis of the EQUATOR study suggests that filgotinib treatment leads to a reduction in inflammation in patients with moderate-to-severe psoriatic arthritis (PsA).
The main findings from this phase 2 trial showed that patients treated with the selective Janus kinase (JAK)1 inhibitor experienced “significant and sustained improvements in clinical signs and symptoms of active PsA as compared to placebo,” said study author Dafna Gladman (University of Toronto, Ontario, Canada) at the EULAR 2020 E-Congress.
The biomarker analysis included serum samples collected at baseline and weeks 1, 4, and 16 from 60 patients treated with filgotinib 200 mg/day and 61 given placebo.
At baseline, Gladman and colleagues observed two distinct clusters of biomarkers. The first, including acute inflammatory markers such as C-reactive protein (CRP) and interleukin (IL)-6, correlated significantly with Disease Activity in Psoriatic Arthritis (DAPSA) scores, whereas the second cluster involved markers from the Th17 pathway, such as IL-17A and IL-22, and correlated with PASI scores.
Gladman explained that the impact of filgotinib on circulating biomarkers was evaluated by comparing the change in biomarker levels from baseline to weeks 1, 4, and 16 in the filgotinib and placebo arms.
In this analysis, there were four separate clusters of biomarker responses. Gladman said that in the first cluster there was a “rapid and substantial” reduction in systemic inflammatory proteins, including CRP and IL-6, two cytokines involved in the JAK-STAT pathway.
In the second and third clusters, the presenter described “modest decreases” in a number of cytokines, chemokines, and cellular adhesion molecules with filgotinib treatment. These included IL-17AF and IL-12 p40, both of which are known to be involved in psoriasis-associated pathology.
Conversely, Gladman said that the fourth cluster included biomarkers that increased with filgotinib treatment, including adiponectin, which “can have anti-inflammatory actions in disease.”
Taken together, these molecular findings “are consistent with reduced disease activity in patients receiving filgotinib treatment, and suggest that filgotinib leads to a rapid and sustained reduction of inflammation in PsA,” concluded Gladman.
And she announced that a phase 3 study of filgotinib for the treatment of PsA is currently underway.
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