{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T05:47:31Z","timestamp":1771307251139,"version":"3.50.1"},"reference-count":31,"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\/"}],"funder":[{"DOI":"10.13039\/100006483","name":"AbbVie","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100006483","id-type":"DOI","asserted-by":"crossref"}]}],"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 evaluate the efficacy and safety of ABT\u2010494, a selective JAK\u20101 inhibitor, in patients with moderate\u2010to\u2010severe rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Three hundred RA patients receiving stable doses of MTX were randomly assigned equally to receive immediate\u2010release ABT\u2010494 at 3, 6, 12, or 18 mg twice daily, 24 mg once daily, or placebo for 12 weeks. The primary efficacy end point was the proportion of patients meeting the American College of Rheumatology 20% improvement criteria (achieving an ACR20 response) at week 12, as determined using the last observation carried forward method.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>At week 12, the proportion of ACR20 responses was higher with ABT\u2010494 (62%, 68%, 80%, 64%, and 76% for the 3, 6, 12, 18, and 24 mg doses, respectively) than with placebo (46%) (using nonresponder imputation) (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05 for the 6, 12, and 24 mg doses). There was a significant dose\u2010response relationship among all ABT\u2010494 doses (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001). The proportions of patients achieving ACR50 and ACR70 responses were significantly higher for all ABT\u2010494 doses (except the 12 mg dose for the ACR70 response) than for placebo, as were changes in the Disease Activity Score in 28 joints using the C\u2010reactive protein level (DAS28\u2010CRP). Rapid improvement was demonstrated by significant differences in ACR20 response rates and changes in the DAS28\u2010CRP for all doses compared with placebo at week 2 (the first postbaseline visit). The incidence of adverse events was similar across groups; most were mild, and infections were the most frequent. One serious infection (community\u2010acquired pneumonia) occurred with ABT\u2010494 at 12 mg. There were dose\u2010dependent increases in high\u2010density lipoprotein (HDL) and low\u2010density lipoprotein (LDL) cholesterol, but the LDL cholesterol:HDL cholesterol ratios were unchanged through week 12. Mean hemoglobin levels remained stable at lower doses, but decreases were observed at higher doses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study evaluated a broad range of doses of ABT\u2010494 in RA patients with an inadequate response to MTX. ABT\u2010494 demonstrated efficacy, with a safety and tolerability profile similar to that of other JAK inhibitors.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.39808","type":"journal-article","created":{"date-parts":[[2016,7,7]],"date-time":"2016-07-07T11:26:27Z","timestamp":1467890787000},"page":"2857-2866","source":"Crossref","is-referenced-by-count":189,"title":["Efficacy and Safety of ABT\u2010494, a Selective JAK\u20101 Inhibitor, in a Phase IIb Study in Patients With Rheumatoid Arthritis and an Inadequate Response to Methotrexate"],"prefix":"10.1002","volume":"68","author":[{"given":"Mark C.","family":"Genovese","sequence":"first","affiliation":[{"name":"Stanford University School of Medicine Palo Alto California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josef S.","family":"Smolen","sequence":"additional","affiliation":[{"name":"Medical University of Vienna and Hietzing Hospital Vienna 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