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

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 DARW...

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Main Authors: Arthur Kavanaugh, Paul Emery, René Westhovens, Mark C Genovese, Kevin L Winthrop, Rieke Alten, Dick de Vries, Lorenzo Dagna, Patrick Verschueren, Maria Greenwald, Regina Cseuz, Robin Besuyen, Vikas Modgill, Ly Huong Le
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Language:English
Published: BMJ Publishing Group 2025-01-01
Series:RMD Open
Online Access:https://rmdopen.bmj.com/content/11/1/e004857.full
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author Arthur Kavanaugh
Paul Emery
René Westhovens
Mark C Genovese
Kevin L Winthrop
Rieke Alten
Dick de Vries
Lorenzo Dagna
Patrick Verschueren
Maria Greenwald
Regina Cseuz
Robin Besuyen
Vikas Modgill
Ly Huong Le
author_facet Arthur Kavanaugh
Paul Emery
René Westhovens
Mark C Genovese
Kevin L Winthrop
Rieke Alten
Dick de Vries
Lorenzo Dagna
Patrick Verschueren
Maria Greenwald
Regina Cseuz
Robin Besuyen
Vikas Modgill
Ly Huong Le
author_sort Arthur Kavanaugh
collection DOAJ
description 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.
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spelling doaj-art-3f0bb0046b7e49cfb5c382af59c467042025-01-31T22:45:10ZengBMJ Publishing GroupRMD Open2056-59332025-01-0111110.1136/rmdopen-2024-004857Safety and efficacy of filgotinib in patients with rheumatoid arthritis: final results of the DARWIN 3 long-term extension studyArthur Kavanaugh0Paul Emery1René Westhovens2Mark C Genovese3Kevin L Winthrop4Rieke Alten5Dick de Vries6Lorenzo Dagna7Patrick Verschueren8Maria Greenwald9Regina Cseuz10Robin Besuyen11Vikas Modgill12Ly Huong Le13School of Medicine, University of California San Diego, La Jolla, California, USAUniversity of Leeds, Leeds Institute of Rheumatic and Musculoskeletal Medicine, Leeds, UKDepartment of Development and Regeneration, Skeletal Biology and Engineering Research Center, KU Leuven, Leuven, BelgiumClinical Development, Gilead Sciences Inc, Foster City, California, USASchool of Medicine, Oregon Health and Science University, Portland, Oregon, USADepartment of Internal Medicine and Rheumatology, Schlosspark Klinik, University Medicine Berlin, Berlin, GermanyClinical Development, Galapagos BV, Leiden, NetherlandsUnit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), Department of Internal Medicine, IRCCS San Raffaele Hospital, Milan, ItalyDepartment of Development and Regeneration, Skeletal Biology and Engineering Research Center, KU Leuven, Leuven, BelgiumDepartment of Rheumatology, Desert Medical Advances, Rancho Mirage, California, USADepartment of Rheumatology, Revita Reumatológiai Kft, Budapest, HungaryClinical Development, Galapagos BV, Leiden, NetherlandsMedical Safety, Galapagos GmbH, Basel, SwitzerlandBiostatistics, Galapagos NV, Mechelen, BelgiumObjectives 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.https://rmdopen.bmj.com/content/11/1/e004857.full
spellingShingle Arthur Kavanaugh
Paul Emery
René Westhovens
Mark C Genovese
Kevin L Winthrop
Rieke Alten
Dick de Vries
Lorenzo Dagna
Patrick Verschueren
Maria Greenwald
Regina Cseuz
Robin Besuyen
Vikas Modgill
Ly Huong Le
Safety and efficacy of filgotinib in patients with rheumatoid arthritis: final results of the DARWIN 3 long-term extension study
RMD Open
title Safety and efficacy of filgotinib in patients with rheumatoid arthritis: final results of the DARWIN 3 long-term extension study
title_full Safety and efficacy of filgotinib in patients with rheumatoid arthritis: final results of the DARWIN 3 long-term extension study
title_fullStr Safety and efficacy of filgotinib in patients with rheumatoid arthritis: final results of the DARWIN 3 long-term extension study
title_full_unstemmed Safety and efficacy of filgotinib in patients with rheumatoid arthritis: final results of the DARWIN 3 long-term extension study
title_short Safety and efficacy of filgotinib in patients with rheumatoid arthritis: final results of the DARWIN 3 long-term extension study
title_sort safety and efficacy of filgotinib in patients with rheumatoid arthritis final results of the darwin 3 long term extension study
url https://rmdopen.bmj.com/content/11/1/e004857.full
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