After 156 weeks of treatment, filgotinib, a highly selective JAK1 inhibitor, was generally well tolerated and no new safety signals emerged, with no safety differences in patients receiving combination therapy with methotrexate (MTX) vs. filgotinib monotherapy.
Efficacy was sustained up to week 156 in both monotherapy and in MTX combination groups.
Filgotinib (FIL) is an oral selective JAK1 inhibitor. In studies to date, FIL was found to be effective and safe in patients with rheumatoid arthritis (RA). [1,2] DARWIN 3 is an ongoing, open-label, long-term extension study of earlier phase 2b studies evaluating the long-term outcomes with FIL in RA.
All patients who were inadequate responders to MTX completing the 24-week DARWIN 1 (FIL + MTX) and DARWIN 2 (FIL monotherapy) studies were eligible to enter DARWIN 3.
Week 156 interim analysis data from the first dose of FIL in the parent studies through 30 May 2018 is presented.
Patients were analyzed by FIL + MTX (from DARWIN 1) or FIL monotherapy (from DARWIN 2).
The event rate was calculated as the total events/total years of exposure of FIL. If the subjects were continuing the study at the time of analysis, the exposure was calculated up to the data cut date.
Of 877 patients completing the parent studies, 739 patients enrolled in DARWIN 3 (497 from DARWIN 1, 242 from DARWIN 2); the majority of patients in DARWIN 1 and 2 were female (81.5%, 81.8%) and white (75.3%, 74.8%) with a mean age of 53 and 52 years, respectively.
The mean baseline MTX dose in the FIL + MTX group was 16.8 mg/week.
At week 156, 59.9% of patients remained on study treatment.
The most common reasons for discontinuation were adverse events (26.5%) and subject request (9.1%).
Total exposure to FIL was 2203 patient years; mean ± standard deviation (SD) exposure was 2.86 ± 1.21 years for FIL + MTX and 3.04 ± 1.22 years for FIL monotherapy.
Treatment-emergent adverse events (TEAEs) occurred in 419 (84.3%) and 203 (83.9%) patients receiving FIL + MTX and FIL monotherapy; serious TEAEs occurred in 45 (9.1%) and 33 (13.6%), respectively.
Event rates of adverse events of special interest, such as serious infections and Herpes zoster infections, remained low at week 156.
There were 5 deaths (meningococcal meningitis, pneumonia, non-Hodgkin’s lymphoma, and deep vein thrombosis with pulmonary embolism); none occurred after the week 132 analysis (2 in FIL + MTX; 3 in FIL monotherapy).
Clinical efficacy up to week 156, as measured by ACR20/50/70 responses, and DAS28(CRP) ≤3.2 and DAS28(CRP) <2.6 are shown in the Figure.
Westhovens R, Taylor PC, Alten R, et al. Filgotinib (GLPG0634/GS-6034), an oral JAK1 selective inhibitor, is effective in combination with methotrexate (MTX) in patients with active rheumatoid arthritis and insufficient response to MTX: results from a randomised, dose-finding study (DARWIN 1). Ann Rheum Dis. 2017 Jun;76(6):998-1008.
Kavanaugh A, Kremer J, Ponce L, 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 Jun;76(6):1009-19.
Presenter disclosure: The presenter has reported relationships with Abbott, Amgen, AstraZeneca, Bristol-Myers Squibb, Celgene, Centocor-Janssen, Eli Lilly, Gilead Sciences, Janssen, Janssen Research & Development, LLC, Novartis, Pfizer, Roche, UCB Pharma.