Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2025 Jan 30;11(1):e004857.
doi: 10.1136/rmdopen-2024-004857.

Safety and efficacy of filgotinib in patients with rheumatoid arthritis: final results of the DARWIN 3 long-term extension study

Rene Westhovens  1 , Kevin L Winthrop  2 , Arthur Kavanaugh  3 , Maria Greenwald  4 , Lorenzo Dagna  5   6 , Regina Cseuz  7 , Robin Besuyen  8 , Dick de Vries  8 , Vikas Modgill  9 , Ly Huong Le  10 , Mark C Genovese  11 , Paul Emery  12   13 , Patrick Verschueren  14   15 , Rieke Alten  16
Affiliations
Clinical Trial

Safety and efficacy of filgotinib in patients with rheumatoid arthritis: final results of the DARWIN 3 long-term extension study

Rene Westhovens et al. RMD Open. .

Abstract

Objectives: DARWIN 3 (ClinicalTrials.gov: NCT02065700) assessed the safety and efficacy of filgotinib in a long-term extension (LTE) of two phase II randomised controlled rheumatoid arthritis (RA) trials.

Methods: Eligible patients completing the 24-week DARWIN 1 (filgotinib plus methotrexate) and DARWIN 2 (filgotinib monotherapy) trials could enrol. Patients received filgotinib 200 mg/day, except 15 men who received filgotinib 100 mg/day. The primary endpoints were safety and tolerability, which were assessed by the incidence of treatment-emergent adverse events (TEAEs). Safety and efficacy analyses included all enrolled patients who received ≥1 dose of filgotinib in DARWIN 3.

Results: 739 patients entered the LTE. The total patient-years of exposure (PYE) to filgotinib was 3706.3 years; the mean exposure duration was 259.8 weeks. 497 patients (67.3%) discontinued prematurely (including 266 TEAEs and 172 withdrawals due to the patient's decision or 'sponsor request'). Overall exposure-adjusted incidence rate (EAIR) was 67 (95% CI 62 to 72.2)/100 PYE for TEAEs and 3.8 (95% CI 3.2 to 4.5)/100 PYE for serious TEAEs. EAIR of infections was 23.3 (95% CI 21.2 to 25.6)/100 PYE, 1.3 (95% CI 0.9 to 1.7)/100 PYE for serious infections and 1.3 (95% CI 0.9 to 1.7)/100 PYE for herpes zoster. EAIRs of major adverse cardiovascular events (0.19 (95% CI 0.8 to 0.39)/100 PYE) and malignancies (0.6 (95% CI 0.4 to 0.9)/100 PYE) were low. Disease response assessed using non-responder imputation plateaued at LTE week 12 before slowly declining over time, with overall American College of Rheumatology (ACR)20/50/70 response rates of 26.9%/20.2%/14.7% at week 396.

Conclusion: Filgotinib was well tolerated in patients with RA for up to 8 years. Safety and efficacy profiles were maintained in patients previously receiving either filgotinib plus methotrexate or filgotinib monotherapy.

Keywords: Antirheumatic Agents; Arthritis; Arthritis, Rheumatoid.

PubMed Disclaimer

Conflict of interest statement

Competing interests: RW reports consultancy fees and speaker fees from Celltrion, Galapagos and Gilead. KLW reports consultancy fees from AbbVie, AstraZeneca, BMS, Galapagos, Gilead, GSK, Lilly, Novartis, Pfizer, Regeneron, Roche, Sanofi and UCB; and grant/research support from BMS and Pfizer. AK reports consultancy fees from Amgen, AbbVie, BMS, Janssen, Novartis, Pfizer and UCB. MG reports grant/research support from AbbVie, Aclaris, Galapagos, Janssen, Lilly and Nimbus. LD reports consultancy fees from AbbVie, Amgen, AstraZeneca, Biogen, Boehringer Ingelheim, BMS, Celltrion, Galapagos, GSK, Janssen, Kiniksa Pharmaceuticals, Lilly, Novartis, Pfizer, Roche, Sanofi-Genzyme, Sobi and Takeda; and grant/research support from AbbVie, BMS, Celgene, GSK, Janssen, Kiniksa Pharmaceuticals, MSD, Mundipharma, Novartis, Pfizer, Roche, Sanofi-Genzyme and Sobi. RC none declared. RB and DdV were employees of, and shareholders in, Galapagos at the time of the study. VM is an employee of, and shareholder in, Galapagos. LHL is an employee of Alfasigma S.p.A. MCG was an employee of, and shareholder in, Gilead at the time of the analysis. PE reports consultancy fees from AbbVie, BMS, Boehringer Ingelheim, Galapagos, Gilead, Lilly and Novartis; speaker fees from AbbVie, BMS, Boehringer Ingelheim, Galapagos, Gilead, Lilly, Novartis and Samsung; and grant/research support from AbbVie, BMS, Lilly, Novartis, Roche and Samsung. PV reports consultancy fees from Alfasigma S.p.A., Boehringer Ingelheim, Cytryl, Galapagos, Lilly, Pfizer and Sidekick Health; speaker fees from AbbVie, Galapagos, Lilly, Medicongress and Roularta; and grant/research support from Galapagos and Pfizer. RA reports consultancy fees from AbbVie, Amgen, Biogen, BMS, Celltrion, Gilead, Janssen, Lilly, Medac, MSD, Mylan, Novartis, Pfizer, Roche, Sandoz, Sanofi-Genzyme, UCB and Viatris.

Figures

Figure 1
Figure 1. Patient disposition. LTE, long-term extension; MTX, methotrexate.
Figure 2
Figure 2. Observed case (left) and NRI (right) analyses for ACR20 (A), ACR50 (B) and ACR70 (C) response rates by LTE visit. Parent study BL value was the last available value collected on or before the first dose of the study drug in the parent studies. The Ex BL value was the last available value collected on or before the first dose of the study drug in the LTE study. ACR20/50/70, 20%/50%/70% improvement in American College of Rheumatology criteria; BL, baseline; Ex, extension; LTE, long-term extension; NRI, non-responder imputation.
Figure 3
Figure 3. Observed case (left) and NRI (right) analyses for proportions of patients with DAS28-CRP<2.6 (A) and observed case analyses for mean DAS28-CRP (B) and mean DAS28-CRP change from parent study baseline (C) by LTE visit. Parent BL value was the last available value collected on or before the first dose of the study drug in the parent studies. The Ex BL value was the last available value collected on or before the first dose of the study drug in the LTE study. BL, baseline; DAS28-CRP, Disease Activity Score in 28 joints using C-reactive protein; Ex, extension; LTE, long-term extension; NRI, non-responder imputation.
Figure 4
Figure 4. Mean HAQ-DI score by visit (A) and mean change from parent study baseline in HAQ-DI score (B). Parent BL value was the last available value collected on or before the first dose of the study drug in the parent studies. Ex BL value was the last available value collected on or before the first dose of the study drug in the LTE study. BL, baseline; Ex, extension; HAQ-DI, Health Assessment Questionnaire–Disability Index; LTE, long-term extension.
See this image and copyright information in PMC

References

    1. Bullock J, Rizvi SAA, Saleh AM, et al. Rheumatoid arthritis: a brief overview of the treatment. Med Princ Pract. 2018;27:501–7. doi: 10.1159/000493390. - DOI - PMC - PubMed
    1. Di Matteo A, Bathon JM, Emery P. Rheumatoid arthritis. Lancet. 2023;402:2019–33. doi: 10.1016/S0140-6736(23)01525-8. - DOI - PubMed
    1. Smolen JS, Landewé RBM, Bergstra SA, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Ann Rheum Dis. 2023;82:3–18. doi: 10.1136/ard-2022-223356. - DOI - PubMed
    1. Scott IC, Machin A, Mallen CD, et al. The extra-articular impacts of rheumatoid arthritis: moving towards holistic care. BMC Rheumatol . 2018;2:32. doi: 10.1186/s41927-018-0039-2. - DOI - PMC - PubMed
    1. Tanaka Y, Luo Y, O’Shea JJ, et al. Janus kinase-targeting therapies in rheumatology: a mechanisms-based approach. Nat Rev Rheumatol. 2022;18:133–45. doi: 10.1038/s41584-021-00726-8. - DOI - PMC - PubMed

Publication types

MeSH terms

Associated data