CHICAGO -- The selective JAK1 inhibitor filgotinib showed promise in the treatment of psoriatic arthritis, according to a randomized phase II proof-of-concept study.
At week 16, among patients with psoriatic arthritis who had not responded adequately to conventional disease-modifying antirheumatic drugs (DMARDs), 20% improvements on the criteria of the ACR (ACR20) were seen in 80% of those who received oral filgotinib, 200 mg/day compared with 33.3% of those who were randomized to placebo (P<0.0001), according to Philip J. Mease, MD, of the University of Washington in Seattle.
In addition, a state of Minimal Disease Activity was achieved at week 16 by 23.1% versus 6.1% (P=0.0212), he reported at the American College of Rheumatology (ACR) annual meeting.
Filgotinib is an investigational, oral, selective JAK1 inhibitor being developed for use in inflammatory diseases. Efficacy has been demonstrated in rheumatoid arthritis (RA) and Crohn's disease.
The current multicenter study included 131 patients (mean age 50) with a mean duration of psoriatic arthritis of 7 years. Mean Health Assessment Questionnaire Disability Index (HAQ-DI) at baseline was 1.40, and mean Psoriasis Area and Severity Index (PASI) was 11.3 in patients who had at least 3% body surface area involvement.
Among patients receiving filgotinib, ACR50 and ACR70 responses were observed in 47.7% and 23.1% compared with 15.2% (P<0.0001) and 6.1% (P=0.0037) of those given placebo. Improvement from baseline on the HAQ-DI of 0.35 points or more was seen in 65.1% of the filgotinib group and 41.9% of the placebo group (P=0.0085).
Among patients who had at least 3% body surface area psoriasis involvement at baseline, a 75% reduction in the PASI was seen in 45.2% of the filgotinib group compared with 15% of the placebo group (P=0.0034).
For those who had enthesitis present at baseline, resolution on the Leeds Enthesitis Index occurred in 51.5% of the filgotinib group compared with 25.6% of the placebo group (P=0.0089), and for those who had dactylitis, resolution on the Leeds Dactylitis Index was observed in 73.7% and 65.5% (P=0.6310).
Overall adverse event rates were 56.9% in the filgotinib group and 59.1% in the placebo group, while infection rates were 21.5% and 21.2%, respectively. The two serious events were a hip fracture in the placebo group and a case of fatal pneumonia in the filgotinib group. No malignancies, venous thromboembolic events, or opportunistic infections were seen, and the sole case of herpes zoster was confined to a single dermatome.
Laboratory changes were consistent with what has been seen in previous RA studies. There was an increase in hemoglobin in the filgotinib, but no grades 2, 3, or 4 decrements noted. There was no significant change in platelet counts, and for lymphocytes there was essentially no mean change, although there were some grade 2 events, one grade 3 in the placebo arm and no grade 4 changes.
'Thus, this study was a promising first step for this agent in this disease," Mease concluded.
Disclosures
Mease disclosed relevant relationships with AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Novartis, Pfizer, Sun, UCB, Galapagos, and Pfizer.
Primary Source
American College of Rheumatology
Mease P, et al 鈥淔ilgotinib, an oral, selective Janus kinase 1 inhibitor, is effective in psoriatic arthritis patients with an inadequate response to conventional disease-modifying antirheumatic drugs: Results from a randomized, placebo-controlled, phase 2 study鈥� ACR 2018; Abstract 1831.