{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T21:04:10Z","timestamp":1789419850337,"version":"build-2803163510"},"reference-count":38,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2017,8,31]],"date-time":"2017-08-31T00:00:00Z","timestamp":1504137600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Gal\u00e1pagos"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2017,10]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>JAK inhibitors have shown efficacy in rheumatoid arthritis (RA). We undertook this study to test our hypothesis that selective inhibition of JAK\u20101 would combine good efficacy with a better safety profile compared with less selective JAK inhibitors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In two 4\u2010week exploratory, double\u2010blind, placebo\u2010controlled phase IIa trials, 127 RA patients with an insufficient response to methotrexate (MTX) received filgotinib (GLPG0634, GS\u20106034) oral capsules (100 mg twice daily or 30, 75, 150, 200, or 300 mg once daily) or placebo, added onto a stable regimen of MTX, to evaluate safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of filgotinib. The primary efficacy end point was the number and percentage of patients in each treatment group meeting the American College of Rheumatology 20% improvement criteria (achieving an ACR20 response) at week 4.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Treatment with filgotinib at 75\u2013300 mg met the primary end point and showed early onset of efficacy. ACR20 response rates progressively increased to week 4, and the Disease Activity Score in 28 joints using the C\u2010reactive protein (CRP) level decreased. Marked and sustained improvements were observed in serum CRP level and other PD markers. The PK of filgotinib and its major metabolite was dose proportional over the 30\u2013300 mg range. Early side effects seen with other less selective JAK inhibitors were not observed (e.g., there was no worsening of anemia [JAK\u20102 inhibition related], no effects on liver transaminases, and no increase in low\u2010density lipoprotein or total cholesterol). A limited decrease in neutrophils without neutropenia was consistent with immunomodulatory effects through JAK\u20101 inhibition. There were no infections. Overall, filgotinib was well tolerated. Events related to study drug were mild or moderate and transient during therapy, and the most common such event was nausea.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Selective inhibition of JAK\u20101 with filgotinib shows initial efficacy in RA with an encouraging safety profile in these exploratory studies.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.40186","type":"journal-article","created":{"date-parts":[[2017,6,16]],"date-time":"2017-06-16T15:36:38Z","timestamp":1497627398000},"page":"1949-1959","source":"Crossref","is-referenced-by-count":76,"title":["Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Filgotinib, a Selective JAK\u20101 Inhibitor, After Short\u2010Term Treatment of Rheumatoid Arthritis: Results of Two Randomized Phase IIa Trials"],"prefix":"10.1002","volume":"69","author":[{"given":"Fr\u00e9d\u00e9ric","family":"Vanhoutte","sequence":"first","affiliation":[{"name":"Gal\u00e1pagos NV Mechelen 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