Results from a randomized placebo-controlled phase 2 study published in The Lancet support the efficacy of filgotinib in treating active psoriatic arthritis (PsA).
Filgotinib is a selective Janus kinase 1 (JAK1) inhibitor taken by mouth. The JAK1 pathway has previously been implicated in the pathogenesis of PsA. Filgotinib is unique in its selectivity for JAK1 over other JAK family members. The EQUATOR trial was a randomized, double-blind, placebo-controlled phase 2 trial that enrolled adults (≥18 years) with active moderate to severe PsA according to the classification for PsA (CASPAR) criteria, an active or documented history of plaque psoriasis, and an insufficient response or intolerance to at least 1 conventional synthetic disease-modifying antirheumatic drug (csDMARD). Patients were enrolled from 25 sites in 7 countries: Belgium, Bulgaria, Czech Republic, Estonia, Poland, Spain, and Ukraine. Participants were randomly assigned to receive either once-daily filgotinib 200 mg or placebo for 16 weeks. Subsequent analyses were stratified by current use of csDMARDs and previous use of anti-tumor necrosis factor. As a primary end point, investigators captured the proportion of patients achieving 20% improvement in American College of Rheumatology response criteria (ACR20) at 16 weeks.
A total of 131 patients were allocated to treatment with either filgotinib (n=65) or placebo (n=66) between March and September 2017. Attrition rates were low, with 92% of patients in the filgotinib group and 97% of patients in the placebo group completing the study. Eighty percent of patients in the filgotinib group achieved ACR20 at 16 weeks compared with just 33% of those in the placebo group (P <.0001).
In addition, more patients treated with filgotinib achieved ACR50 (P <.0001) and ACR70 (P =.0037) compared with those treated with placebo. Patients who continued receiving csDMARD therapy and who received filgotinib also achieved ACR20 and ACR50 at greater rates than their placebo counterparts. Treatment-emergent adverse events were reported by 57% of patients receiving filgotinib and 59% of patients receiving placebo. Filgotinib was well-tolerated by most study participants, with participants typically reporting mild to moderate adverse events requiring no intervention. The most commonly reported events included nasopharyngitis and headache, which occurred at similar rates across study groups. Just 6 participants experienced an adverse event of grade 3 or worse, and 1 fatal treatment-emergent event (pneumonia) was reported in the filgotinib group. A serious treatment-emergency event was reported in the placebo group as well, although it was not fatal.
These data suggest that filgotinib is effective in treating PsA symptoms through selective JAK1 inhibition. The safety profile of the drug was confirmed to be similar to prior reports, with no new adverse events identified. Although further research is necessary to evaluate the precise mechanisms of filgotinib and its efficacy in treating additional arthritic symptoms, these data are promising for its utility in PsA.
Mease P, Coates LC, Helliwell PS, et al. Efficacy and safety of filgotinib, a selective Janus kinase 1 inhibitor, in patients with active psoriatic arthritis (EQUATOR): results from a randomised, placebo-controlled, phase 2 trial [published online October 22, 2018]. Lancet. doi: 10.1016/S0140-6736(18)32483-8