Analysis Demonstrates Long-Term Safety Profile of Filgotinib for RA Treatment

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The incidences of adverse events were comparable between the original and current analyses of patients with moderate to severe RA treated with filgotinib.

The safety profile of filgotinib remained stable more than 4 years among a cohort of patients with moderate to severe rheumatoid arthritis (RA), according to an updated integrated safety analysis presented at the 2024 European Congress of Rheumatology (EULAR).1 These results were comparable to a previous analysis and no new safety information regarding adverse events of special interest (AESIs) were reported.

“The oral Janus kinase (JAK) 1-preferential inhibitor filgotinib is approved at doses of 100 mg (FIL100) and 200 mg (FIL200) for the treatment of moderate to severe active RA,” wrote a team of investigators led by Kevin Winthrop, MD, MPH, professor of Public Health at the Oregon Health and Science University, School of Medicine.1 “Previous integrated safety analyses from clinical trials have shown that safety and tolerability is broadly similar between the FIL doses, with a lower incidence of herpes zoster with FIL100 vs FIL200.”

To update a previous analysis on selected treatment-emergent adverse events for filgotinib, investigators used data from 7 clinical trials:

  • Two phase 2 DARWIN studies
  • Three phase 3 FINCH studies
  • The long-term extension (LTE) DARWIN 3 study
  • The LTE FINCH 4 study

Briefly, the FINCH study was a 52-week, multicenter, double-blind, placebo- and active-controlled phase 3 trial that assessed the safety and efficacy of oral filgotinib in patients with RA. These patients were randomized 3:3:2:3 to receive FIL200, FIL100, subcutaneous adalimumab 40 mg biweekly, or placebo (through week 24), with concomitant background methotrexate.2

The 24-week, phase 2b DARWIN trial enrolled patients with moderate to severe active RA who were randomized to receive 50, 100, or 200 mg filgotinib once daily or placebo, following a ≥ 4-week break from methotrexate.3

These data provided a median exposure of 4.3 years and maximum of 8.3 years. Exposure-adjusted incidence rates (EAIRs)/100 patient-years of exposure (PYE) were evaluated for nonmelanoma skin cancer (NMSC), malignancies (except for NMSC), arterial systemic thromboembolism (ASTE), major adverse cardiovascular events (MACE), herpes zoster, venous thromboembolism (VTE), serious infections, and deaths. These data were extracted from the completed studies and up until May 8, 2023.1

A total of 3691 patients with moderate to severe RA receiving filgotinib were included in the analysis, with a total exposure of 14,127 PYE. The median exposure was 3.6 years among patients receiving FIL100 and 4.4 years for the FIL200 group. The maximum exposure for FIL100 and FIL200 was 8.1 years and 8.3 years, respectively. Baseline demographics and disease characteristics were comparable between groups.1

Ultimately, the incidences of AESIs were comparable between the original data cut in 2022 and the current analysis. These included MACE, ASTE, NMSC, VTE, herpes zoster, malignancies, serious infections, and all-cause mortality.1

The EAIR (95% confidence interval [CI])/100 PYE of serious infections was 2.2 (1.8, 2.6) in the FIL100 cohort and 1.7 (1.5, 2.0) in the FIL200 cohort. The EAIR (95% CI)/100 PYE of herpes zoster was 1.1 (.8, 1.4) and 1.4 (1.2, 1.7) in the FIL100 and FIL200 groups, respectively. Over a 312-week period, the risk of all-cause mortality was comparable between FIL100 and FIL200.1

The duration of exposure was shorter in the FIL100 group compared with the FIL200 group (5202.2 PYE vs 8924.5 PYE, respectively) due to study designs. Therefore, Winthrop and his team warn comparisons of EAIRs between dosing groups should be made with caution.1


  1. Winthrop KL, Aletaha D, Caporali RF, Tanaka Y, et al. An Update on the Integrated Safety Analysis of Filgotinib in Patients with Moderate to Severe Active Rheumatoid Arthritis Over a Median of 4.3 Years. Presented at: EULAR. Vienna, Austria. June 12 – 15, 2024.
  2. Combe B, Kivitz A, Tanaka Y, et al. Filgotinib versus placebo or adalimumab in patients with rheumatoid arthritis and inadequate response to methotrexate: a phase III randomised clinical trial. Ann Rheum Dis. 2021;80(7):848-858. doi:10.1136/annrheumdis-2020-219214
  3. 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;76(6):1009-1019. doi:10.1136/annrheumdis-2016-210105