{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T15:51:56Z","timestamp":1793721116466,"version":"4.6.1"},"reference-count":32,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T00:00:00Z","timestamp":1738195200000},"content-version":"unspecified","delay-in-days":29,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Alfasigma S.p.A."},{"DOI":"10.13039\/100019832","name":"Gal\u00e1pagos","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100019832","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005564","name":"Gilead Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005564","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2024,10,27]]},"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>DARWIN 3 (ClinicalTrials.gov: <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT02065700\">NCT02065700<\/jats:ext-link>) assessed the safety and efficacy of filgotinib in a long-term extension (LTE) of two phase II randomised controlled rheumatoid arthritis (RA) trials.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>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 \u22651\u2009dose of filgotinib in DARWIN 3.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>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\u2019s decision or \u2018sponsor request\u2019). 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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/rmdopen-2024-004857","type":"journal-article","created":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T10:00:20Z","timestamp":1738231220000},"page":"e004857","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":10,"title":["Safety and efficacy of filgotinib in patients with rheumatoid arthritis: final results of the DARWIN 3 long-term extension study"],"prefix":"10.1136","volume":"11","clinical-trial-number":[{"clinical-trial-number":"nct02065700","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct01888874","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct01894516","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct02065700","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04871919","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3432-3073","authenticated-orcid":false,"given":"Rene","family":"Westhovens","sequence":"first","affiliation":[{"name":"Department of Development and Regeneration, Skeletal Biology and Engineering Research Center, KU Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3892-6947","authenticated-orcid":false,"given":"Kevin L","family":"Winthrop","sequence":"additional","affiliation":[{"name":"School of Medicine, Oregon Health and Science University, Portland, Oregon, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6942-5830","authenticated-orcid":false,"given":"Arthur","family":"Kavanaugh","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Autoimmunity and Inflammation, University of California San Diego, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2622-1448","authenticated-orcid":false,"given":"Maria","family":"Greenwald","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Desert Medical Advances, Rancho Mirage, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7428-315X","authenticated-orcid":false,"given":"Lorenzo","family":"Dagna","sequence":"additional","affiliation":[{"name":"Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), Department of Internal Medicine, IRCCS San Raffaele Hospital, Milan, Italy"},{"name":"Department of Internal Medicine, Medical School, Vita-Salute San Raffaele University, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regina","family":"Cseuz","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Revita Reumatol\u00f3giai Kft, Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8699-4549","authenticated-orcid":false,"given":"Robin","family":"Besuyen","sequence":"additional","affiliation":[{"name":"Clinical Development, Galapagos BV, Leiden, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7637-5840","authenticated-orcid":false,"given":"Dick","family":"de Vries","sequence":"additional","affiliation":[{"name":"Clinical Development, Galapagos BV, Leiden, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9036-5190","authenticated-orcid":false,"given":"Vikas","family":"Modgill","sequence":"additional","affiliation":[{"name":"Medical Safety, Galapagos GmbH, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6566-2189","authenticated-orcid":false,"given":"Ly Huong","family":"Le","sequence":"additional","affiliation":[{"name":"Biostatistics, Galapagos NV, Mechelen, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5294-4503","authenticated-orcid":false,"given":"Mark C","family":"Genovese","sequence":"additional","affiliation":[{"name":"Clinical Development, Gilead Sciences Inc, Foster City, California, 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