{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T02:55:44Z","timestamp":1785034544944,"version":"3.55.0"},"reference-count":29,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,12,23]],"date-time":"2015-12-23T00:00:00Z","timestamp":1450828800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Vertex Pharmaceuticals Incorporated"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis & Rheumatology"],"published-print":{"date-parts":[[2016,1]]},"abstract":"Objective<\/jats:title>To assess the efficacy and safety of decernotinib (VX\u2010509), an oral selective inhibitor of JAK\u20103, in patients with rheumatoid arthritis (RA) in whom the response to methotrexate treatment was inadequate.<\/jats:p><\/jats:sec>Methods<\/jats:title>In this 24\u2010week, double\u2010blind, randomized phase IIb study, 358 patients with active RA received either placebo (n\u2009=\u200971) or VX\u2010509 at dosages of 100 mg\/day (n\u2009=\u200971), 150 mg\/day (n\u2009=\u200972), 200 mg\/day (n\u2009=\u200972), or 100 mg twice daily (n\u2009=\u200972). Primary measures of efficacy at week 12 were the response rate according to the American College of Rheumatology 20% improvement criteria (ACR20) and change from baseline in the Disease Activity Score in 28 joints using the C\u2010reactive protein level (DAS28\u2010CRP).<\/jats:p><\/jats:sec>Results<\/jats:title>At week 12, the ACR20 response rates were 46.5%, 66.7%, 56.9%, and 68.1% in the groups receiving VX\u2010509 at dosages of 100 mg\/day, 150 mg\/day, 200 mg\/day, and 100 mg twice daily, respectively, and 18.3% in the placebo group (P<\/jats:italic> < 0.001 for all comparisons). At week 12, the mean change from baseline in the DAS28\u2010CRP was significantly greater in each VX\u2010509 group compared with the placebo group (P<\/jats:italic> < 0.001). Improvements were maintained at week 24, as shown by the ACR20, ACR50, and ACR70 response rates and mean change from baseline in the DAS28\u2010CRP. The most common adverse event in the VX\u2010509 group was headache (8.7%), and elevated levels of transaminases, lipoproteins, and creatinine were observed.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>VX\u2010509 significantly improved the signs and symptoms of RA at weeks 12 and 24 compared with the placebo group when it was administered in combination with methotrexate. Safety signals included infection and increases in liver transaminase and lipid levels.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.39473","type":"journal-article","created":{"date-parts":[[2015,10,16]],"date-time":"2015-10-16T16:04:33Z","timestamp":1445011473000},"page":"46-55","source":"Crossref","is-referenced-by-count":119,"title":["VX\u2010509 (Decernotinib), an Oral Selective JAK\u20103 Inhibitor, in Combination With Methotrexate in Patients With Rheumatoid Arthritis"],"prefix":"10.1002","volume":"68","author":[{"given":"Mark C.","family":"Genovese","sequence":"first","affiliation":[{"name":"Stanford University Palo Alto California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald F.","family":"van Vollenhoven","sequence":"additional","affiliation":[{"name":"Karolinska Institute Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9sar","family":"Pacheco\u2010Tena","sequence":"additional","affiliation":[{"name":"Universidad Aut\u00f3noma de Chihuahua Chihuahua Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanqiong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Vertex Pharmaceuticals Incorporated Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nils","family":"Kinnman","sequence":"additional","affiliation":[{"name":"Vertex Pharmaceuticals Incorporated Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,12,23]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S25426"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.23148"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2008.00754.x"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2005.037929"},{"key":"e_1_2_8_6_1","first-page":"2415","article-title":"JAK3: a novel JAK kinase associated with terminal differentiation of hematopoietic cells","volume":"9","author":"Rane SG","year":"1994","journal-title":"Oncogene"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.16.1.293"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.38949"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780310302"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780380602"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keh297"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2007.084459"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.30634"},{"issue":"43","key":"e_1_2_8_14_1","first-page":"S\u201029","article-title":"DAS remission cut points","volume":"24","author":"Fransen J","year":"2006","journal-title":"Clin Exp Rheumatol"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780230202"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.33383"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.37711"},{"key":"e_1_2_8_18_1","unstructured":"Common Terminology Criteria for Adverse Events (CTCAE). 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