{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T23:57:49Z","timestamp":1790467069666,"version":"4.1.0"},"reference-count":33,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2016,11,28]],"date-time":"2016-11-28T00:00:00Z","timestamp":1480291200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2016,12]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To compare the efficacy and safety of ABT\u2010494, a novel selective JAK\u20101 inhibitor, with placebo in patients with moderate\u2010to\u2010severe rheumatoid arthritis (RA) and an inadequate response or intolerance to at least 1 anti\u2013tumor necrosis factor (anti\u2010TNF) agent.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this 12\u2010week, double\u2010blind, placebo\u2010controlled, dose\u2010ranging study, 276 RA patients receiving a stable dose of methotrexate (MTX) who had previously received treatment with at least 1 anti\u2010TNF agent were randomized equally to receive immediate\u2010release ABT\u2010494 at 3, 6, 12, or 18 mg twice daily or matching placebo twice daily. The primary end point was the proportion of patients meeting the American College of Rheumatology 20% improvement criteria (achieving an ACR20 response) at week 12.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>At week 12, significantly more patients receiving ABT\u2010494 (53\u201371%) than those receiving placebo (34%) achieved an ACR20 response (by nonresponder imputation analysis) (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05), with a dose\u2010response relationship among all ABT\u2010494 doses (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001). ACR50 and ACR70 response rates were significantly higher in those receiving ABT\u2010494 (36\u201342% and 22\u201326%, respectively) than in those receiving placebo (16% and 4%, respectively). Changes from baseline in the Disease Activity Score in 28 joints using the C\u2010reactive protein level (DAS28\u2010CRP) were significantly greater for all doses of ABT\u2010494 than for placebo (<jats:italic>P<\/jats:italic>\u2009\u2264\u20090.01). Onset of action of ABT\u2010494 was rapid, with significant differences from placebo at week 2 both in ACR20 response rate (for 12 and 18 mg) and in change in the DAS28\u2010CRP (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001 for 6\u201318 mg). The most frequent adverse events (AEs) were headache, nausea, upper respiratory tract infection, and urinary tract infection. Infection rates were higher at higher doses of ABT\u2010494, but no infections were serious. No deaths were reported among those receiving ABT\u2010494.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In patients with an inadequate response or intolerance to anti\u2010TNF agents, ABT\u2010494 added to MTX showed rapid, dose\u2010dependent improvements in RA signs and symptoms, with safety and tolerability similar to those of other drugs of this class. No new AEs were identified.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.39801","type":"journal-article","created":{"date-parts":[[2016,7,7]],"date-time":"2016-07-07T11:18:55Z","timestamp":1467890335000},"page":"2867-2877","source":"Crossref","is-referenced-by-count":165,"title":["A Phase IIb Study of ABT\u2010494, a Selective JAK\u20101 Inhibitor, in Patients With Rheumatoid Arthritis and an Inadequate Response to Anti\u2013Tumor Necrosis Factor Therapy"],"prefix":"10.1002","volume":"68","author":[{"given":"Joel M.","family":"Kremer","sequence":"first","affiliation":[{"name":"Albany Medical College Albany New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Emery","sequence":"additional","affiliation":[{"name":"University of Leeds and Leeds Teaching Hospitals NHS Trust Leeds UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi S.","family":"Camp","sequence":"additional","affiliation":[{"name":"AbbVie North Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Friedman","sequence":"additional","affiliation":[{"name":"AbbVie North Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Wang","sequence":"additional","affiliation":[{"name":"AbbVie North Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed A.","family":"Othman","sequence":"additional","affiliation":[{"name":"AbbVie North Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nasser","family":"Khan","sequence":"additional","affiliation":[{"name":"AbbVie North Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aileen L.","family":"Pangan","sequence":"additional","affiliation":[{"name":"AbbVie North Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Jungerwirth","sequence":"additional","affiliation":[{"name":"AbbVie North Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward C.","family":"Keystone","sequence":"additional","affiliation":[{"name":"Mount Sinai Hospital, University of Toronto Toronto, Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,11,28]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1517\/14728214.2013.807339"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2005.045062"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2012-202576"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.5.2623"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1310476"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)61424-X"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-159-4-201308200-00006"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1109071"},{"key":"e_1_2_8_10_1","first-page":"508","article-title":"Tofacitinib or adalimumab versus placebo in rheumatoid arthritis [published erratum appears","volume":"367","author":"Vollenhoven RF","year":"2012","journal-title":"in N Engl J Med 2013;369:293]. 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