Filgotinib is efficacious and safe in PsA

Data from the phase 2 study (EQUATOR-trial) shows that filgotinib is efficacious and safe in patients with psoriatic arthritis (PsA) [1]. “The selected Janus kinase (JAK)1 inhibitor improves multiple domains of PsA. No new safety data were obtained. This drug will be explored further in future PsA trials,” concluded Prof. Philip Mease (Swedish Medical Center and University of Washington, Seattle, USA) [2].

Filgotinib is an oral, selective JAK1 inhibitor in development for the treatment of several inflammatory diseases [1]. Prof. Mease et al. aimed to evaluate the onset and maintenance of response to filgotinib vs placebo in the EQUATOR trial by evaluating patient-level response over time. “What we are doing with this analysis is looking in a novel way at treatment response,” he said. The primary objective was to evaluate the time to first response on patient-level and the individual duration of response, compared with placebo. The secondary objectives were to review the overall data on various clinical domains in PsA with filgotinib versus placebo.

The EQUATOR trial was a 16-week, multicentre, randomised, double-blind trial. Eligible patients (aged ≥18 years) had active PsA (≥5 tender joint count and ≥5 swollen joint count), fulfilled classification for PsA (CASPAR) criteria, and had active or a history of plaque psoriasis. They revealed an inadequate response or intolerance to at least one conventional synthetic disease-modifying anti-rheumatic drug (csDMARD). “Patients could have been exposed to previous biologic DMARDs,” Prof. Mease said. PsA patients (n=131) were randomised 1:1 to receive filgotinib 200 mg or placebo once daily. Disease activity was assessed at screening on day 1 and at weeks 1, 2, 4, 8, 12, and 16. Demographics and baseline characteristics were similar between patients receiving filgotinib versus placebo. The primary efficacy point was the proportion of patients achieving ACR20 response. Response maintenance was assessed by analysing ACR20 response patterns over time in both groups. Secondary endpoints included ACR50 and ACR70 response rates linked to changes over time. Other measures presented at EULAR 2019 included change in DAPSA score and HAQ-DI.

Filgotinib did significantly better than placebo related to its efficacy; 80% of the patients achieved an ACR20 response; 47% ACR50, and 23% ACR70. “Fairly distinguishable from placebo,” added Prof. Mease. The onset of response to filgotinib was early, with a median time to first ACR20 response of 4.07 weeks (95% CI 2.29-4.14) in the filgotinib group compared with 12.3 weeks in the placebo group. There were also more occurrences of the response being lost over time and fewer cases of regaining a lost response in the placebo group. More patients achieved ACR50/70 responses more quickly and in greater numbers in the filgotinib group as compared with patients receiving placebo. The mean change from baseline in DAPSA score at week 16 was -27.9 for filgotinib and -18.1 for placebo (P<0.0001). Filgotinib also had a beneficial effect on patient-reported HAQ-DI score. Prof. Mease briefly commented on potential beneficial effects of filgotinib on pruritus, commonly ignored by rheumatologists. With regards to safety, “nothing unexpected was reported.” There were a handful of infections, including one herpes zoster infection, and no venous thromboembolism events. There was one case of death due to anaemia.

1. Mease P, et al. Lancet. 2018 Dec 1;392(10162):2367-2377.
2.  Mease PJ, et al. Abstract OP0109. EULAR 2019

Posted on 4 September, 20191 February, 2024