J Rheumatol 2021 Feb 1. Epub 2021 Feb 1.
A. Kavanaugh has received consulting fees from Gilead Sciences. R. R. Westhovens has received consulting fees from Celltrion, Galapagos, Gilead Sciences, Bristol Myers Squibb, and Roche. K. L. Winthrop has received consulting fees from Gilead Sciences, Galapagos, AbbVie, Lilly,and Pfizer. S. J. Lee, Y. Tan, D. An, L. Ye, and J. S. Sundy are employees of Gilead Sciences, Inc. R. Besuyen and L. Meuleners are employees of Galapagos NV. M. Stanislavchuk and A. J. Spindler report no disclosures. M. Greenwald, MD, has received consulting fees from Celgene, Bristol Myers Squibb, Gilead Sciences, Lilly, Pfizer, AbbVie, Fuji, and Novartis. R. Alten has received consulting fees from Gilead Sciences and Galapagos.M. C. Genovese has received consulting fees from Galapagos, AbbVie, Lilly, Pfizer, and Gilead Sciences. A. Kavanaugh, MD, University of California, San Diego, La Jolla, California; R. R. Westhovens, MD, PhD, KU Leuven, Skeletal Biology and Engineering Research Center, Leuven, Belgium; K. L. Winthrop, MD, MPH, Oregon Health and Science University, Portland, Oregon; S. J. Lee, MD, Y. Tan, PhD, D. An, PhD, L. Ye, PhD, J. S. Sundy, MD, PhD, Gilead Sciences, Inc., Foster City, California; R. Besuyen, MD, L. Meuleners, MS, Galapagos NV, Mechelen, Belgium; M. Stanislavchuk, MD, National Pirogov Memorial Medical University, Vinnytsya, Ukraine; A. J. Spindler, MD, Centro Medico Privado de Reumatologia, San Miguel de Tucuman, Argentina; M. Greenwald, MD, Desert Medical Advances, Palm Desert, California; R. Alten, MD, Schlosspark Klinik, University Medicine Berlin, Berlin, Germany; M. C. Genovese, MD, Stanford University School of Medicine, Division of Immunology & Rheumatology, Stanford, California, and Gilead Sciences, Inc., Foster City, California. Address correspondence to: Prof. Arthur Kavanaugh, MD, Center for Innovative Therapy, Division of Rheumatology, Allergy & Immunology, University of California San Diego School of Medicine, 9500 Gilman Drive, #0943, La Jolla, CA 92093, US. E-mail:
Objective: The long-term safety and efficacy of filgotinib (from phase 2 studies), with or without methotrexate (MTX), for the treatment of patients with rheumatoid arthritis was assessed in DARWIN 3, a long-term, open-label extension study (NCT02065700).
Methods: Eligible patients completing the 24-week DARWIN 1 (filgotinib + MTX) and DARWIN 2 (filgotinib monotherapy) studies entered DARWIN 3, where they received filgotinib 200 mg/day, except for 15 men who received filgotinib 100 mg/day. Safety analyses were performed using the safety analysis set and exposure-adjusted incidence rate (EAIR) of treatment-emergent adverse events (TEAEs) was calculated. Efficacy was assessed from baseline in the parent studies.
Results: Of 790 patients completing the phase 2 parent studies, 739 enrolled in the study. Through April 2019, 59.5% of patients had received ≥4 years of study drug. Mean (SD) exposure to filgotinib was 3.55 (1.57) years in the filgotinib + MTX group and 3.38 (1.59) years in the filgotinib monotherapy group. EAIR per 100 patient years of exposure (PYE) for TEAEs was 24.6 in the filgotinib + MTX group and 25.8 in the filgotinib monotherapy group, and for serious TEAEs, the EAIR was 3.1 and 4.3, respectively. ACR20/50/70 responses among patients remaining in the study could be maintained through 4 years, with 89.3%/69.6%/49.1% of filgotinib + MTX group and 91.8%/69.4%/44.4% of monotherapy group maintaining ACR20/50/70 responses based on observed data.
Conclusion: Filgotinib was well tolerated with a 4-year safety profile comparable to that of the parent trials, both in patients receiving combination therapy with MTX or as monotherapy.