{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T20:03:47Z","timestamp":1787169827507,"version":"build-2736575974"},"reference-count":42,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2005,3,4]],"date-time":"2005-03-04T00:00:00Z","timestamp":1109894400000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2005,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Gout affects \u223c1\u20132% of the American population. Current options for treating hyperuricemia in chronic gout are limited. The purpose of this study was to assess the safety and efficacy of febuxostat, a nonpurine selective inhibitor of xanthine oxidase, in establishing normal serum urate (sUA) concentrations in gout patients with hyperuricemia (\u22658.0 mg\/dl).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a phase II, randomized, double\u2010blind, placebo\u2010controlled trial in 153 patients (ages 23\u201380 years). Subjects received febuxostat (40 mg, 80 mg, 120 mg) or placebo once daily for 28 days and colchicine prophylaxis for 14 days prior to and 14 days after randomization. The primary end point was the proportion of subjects with sUA levels &lt;6.0 mg\/dl on day 28.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Greater proportions of febuxostat\u2010treated patients than placebo\u2010treated patients achieved an sUA level &lt;6.0 mg\/dl at each visit (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.001 for each comparison). The targeted sUA level was attained on day 28 in 0% of those taking placebo and in 56% of those taking 40 mg, 76% taking 80 mg, and 94% taking 120 mg of febuxostat. The mean sUA reduction from baseline to day 28 was 2% in the placebo group and 37% in the 40\u2010mg, 44% in the 80\u2010mg, and 59% in the 120\u2010mg febuxostat groups. Gout flares occurred with similar frequency in the placebo (37%) and 40\u2010mg febuxostat (35%) groups and with increased frequency in the higher dosage febuxostat groups (43% taking 80 mg; 55% taking 120 mg). During colchicine prophylaxis, gout flares occurred less frequently (8\u201313%). Incidences of treatment\u2010related adverse events were similar in the febuxostat and placebo groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Treatment with febuxostat resulted in a significant reduction of sUA levels at all dosages. Febuxostat therapy was safe and well tolerated.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.20935","type":"journal-article","created":{"date-parts":[[2005,3,4]],"date-time":"2005-03-04T10:51:02Z","timestamp":1109933462000},"page":"916-923","source":"Crossref","is-referenced-by-count":219,"title":["Febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase: A twenty\u2010eight\u2013day, multicenter, phase II, randomized, double\u2010blind, placebo\u2010controlled, dose\u2010response clinical trial examining safety and efficacy in patients with gout"],"prefix":"10.1002","volume":"52","author":[{"given":"Michael A.","family":"Becker","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"H. Ralph","family":"Schumacher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert L.","family":"Wortmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia A.","family":"MacDonald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William A.","family":"Palo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise","family":"Eustace","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Vernillet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Joseph\u2010Ridge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,3,4]]},"reference":[{"key":"e_1_2_5_2_2","first-page":"2158","volume-title":"Harrison's principles of internal medicine","author":"Wortmann RL","year":"1998"},{"key":"e_1_2_5_3_2","first-page":"2513","volume-title":"The metabolic and molecular bases of inherited disease","author":"Becker MA","year":"2001"},{"key":"e_1_2_5_4_2","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/S0889-857X(21)00971-6","article-title":"Clinical aspects of monosodium urate monohydrate crystal deposition disease (gout)","volume":"14","author":"Becker MA","year":"1988","journal-title":"Rheum Dis Clin North Am"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(87)90441-4"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(67)90004-6"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002281-200205000-00015"},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002281-200105000-00016"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4615-5381-6_3"},{"key":"e_1_2_5_10_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199602153340707"},{"key":"e_1_2_5_11_2","first-page":"577","article-title":"Treatment of chronic gout: can we determine when urate stores are depleted enough to prevent attacks of gout?","volume":"28","author":"Li\u2010Yu J","year":"2001","journal-title":"J Rheumatol"},{"key":"e_1_2_5_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.10511"},{"key":"e_1_2_5_13_2","first-page":"337","article-title":"Diagnosis and management of gout","volume":"10","author":"Chen LX","year":"2003","journal-title":"J Clin Outcomes Management"},{"key":"e_1_2_5_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(74)90634-2"},{"key":"e_1_2_5_15_2","first-page":"227","article-title":"Decreasing prevalence of tophaceous gout","volume":"50","author":"O'Duffy JD","year":"1975","journal-title":"Mayo Clin Proc"},{"key":"e_1_2_5_16_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M208307200"},{"issue":"9","key":"e_1_2_5_17_2","first-page":"S531","article-title":"Effect of febuxostat, a novel non\u2010purine, selective inhibitor of xanthine oxidase (NP\u2010SIXO), on enzymes in purine and pyrimidine metabolism pathway","volume":"48","author":"Zhao L","year":"2003","journal-title":"Arthritis Rheum"},{"key":"e_1_2_5_18_2","first-page":"307","article-title":"A comparative study on the hypouricemic activity and potency in renal xanthine calculus formation of two xanthine oxidase\/xanthine dehydrogenase inhibitors: TEI\u20106720 and allopurinol in rats","volume":"104","author":"Horiuchi H","year":"1999","journal-title":"Res Commun Mol Pathol Pharmacol"},{"key":"e_1_2_5_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(93)90201-R"},{"key":"e_1_2_5_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(93)90033-E"},{"key":"e_1_2_5_21_2","doi-asserted-by":"publisher","DOI":"10.1081\/NCN-200027372"},{"issue":"9","key":"e_1_2_5_22_2","first-page":"S529","article-title":"Effect of renal impairment on pharmacokinetics, pharmacodynamics, and safety of febuxostat (TMX\u201067), a novel non\u2010purine selective inhibitor of xanthine oxidase","volume":"48","author":"Swan S","year":"2003","journal-title":"Arthritis Rheum"},{"key":"e_1_2_5_23_2","volume-title":"Allopurinol tablets, USP","year":"2001"},{"key":"e_1_2_5_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780200320"},{"key":"e_1_2_5_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/biomet\/75.4.800"},{"key":"e_1_2_5_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(68)90210-6"},{"key":"e_1_2_5_27_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcp030733"},{"key":"e_1_2_5_28_2","first-page":"2314","volume-title":"Arthritis and allied conditions: a textbook of rheumatology","author":"Edwards NL","year":"2001"},{"key":"e_1_2_5_29_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.57.9.545"},{"key":"e_1_2_5_30_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11926-001-0048-8"},{"key":"e_1_2_5_31_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1445-5994.2000.tb00857.x"},{"key":"e_1_2_5_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(84)90743-5"},{"key":"e_1_2_5_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(92)90236-5"},{"key":"e_1_2_5_34_2","doi-asserted-by":"publisher","DOI":"10.1177\/106002809302700317"},{"key":"e_1_2_5_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780290111"},{"key":"e_1_2_5_36_2","first-page":"1621","article-title":"Should patients with interval gout be treated with urate lowering drugs?","volume":"22","author":"Fam AG","year":"1995","journal-title":"J Rheumatol"},{"key":"e_1_2_5_37_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.20405"},{"key":"e_1_2_5_38_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197011262832201"},{"key":"e_1_2_5_39_2","first-page":"696","article-title":"Mechanism of allopurinol\u2010mediated inhibition of pyrimidine biosynthesis","volume":"78","author":"Beardmore TD","year":"1971","journal-title":"J Lab Clin Med"},{"key":"e_1_2_5_40_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01968126"},{"key":"e_1_2_5_41_2","first-page":"126","article-title":"Effects of a xanthine oxidase inhibitor on thiopurine metabolism, hyperuricemia, and gout","volume":"76","author":"Rundles RW","year":"1963","journal-title":"Trans Assoc Am Physicians"},{"key":"e_1_2_5_42_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.168.3933.861"},{"key":"e_1_2_5_43_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.169.3943.388"}],"container-title":["Arthritis &amp; Rheumatism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.20935","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.20935","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T17:03:10Z","timestamp":1697043790000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/art.20935"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,3]]},"references-count":42,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2005,3]]}},"alternative-id":["10.1002\/art.20935"],"URL":"https:\/\/doi.org\/10.1002\/art.20935","archive":["Portico"],"relation":{},"ISSN":["0004-3591","1529-0131"],"issn-type":[{"value":"0004-3591","type":"print"},{"value":"1529-0131","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,3]]}}}