{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T02:31:51Z","timestamp":1790303511770,"version":"4.1.0"},"reference-count":25,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2007,2,27]],"date-time":"2007-02-27T00:00:00Z","timestamp":1172534400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2007,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To evaluate the efficacy, immunogenicity, and tolerability of intravenous (IV) PEGylated recombinant mammalian urate oxidase (PEG\u2010uricase) for the treatment of severe gout.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Single infusions of PEG\u2010uricase (at doses ranging from 0.5 mg to 12 mg) were administered to 24 patients (6 cohorts of 4 patients each) in a phase I clinical trial. Plasma uricase activity (pUox), the plasma urate concentration (pUAc), and the uric acid\u2013to\u2010creatinine ratio (UAc:Cr) in urine were monitored for 21 days after dosing. Adverse events and the IgG antibody response to PEG\u2010uricase were followed up for 35 days.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All patients completed the trial. Maximum pUox was linearly related to the IV dose of PEG\u2010uricase, the area under the curve (AUC) value increased linearly (up to a dose of 8 mg), and the pUox half\u2010life was 6.4\u201313.8 days. After doses of 4\u201312 mg, the pUAc fell within 24\u201372 hours, from a mean \u00b1 SD value of 11.1 \u00b1 0.6 mg\/dl to 1.0 \u00b1 0.5 mg\/dl; the AUC value for the pUAc was equivalent to maintaining the pUAc at 1.2\u20134.7 mg\/dl for 21 days postinfusion. The UAc:Cr ratio in urine fell in parallel with the pUAc. IgG antibodies to PEG\u2010uricase, mostly IgG2 and specific for PEG, developed in 9 patients, who had more rapid enzyme clearance but no allergic reactions. All adverse events were mild to moderate, with gout flares being most common.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The bioavailability, efficacy, and tolerability of IV PEG\u2010uricase were greater than the bioavailability, efficacy, and tolerability observed in a previous phase I trial of subcutaneous PEG\u2010uricase. Infusing 4\u201312 mg of PEG\u2010uricase every 2\u20134 weeks should maintain the pUAc well below the therapeutic target of 6 mg\/dl and greatly reduce renal uric acid excretion. This treatment could be effective in depleting expanded tissue urate stores in patients with chronic or tophaceous gout.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.22403","type":"journal-article","created":{"date-parts":[[2007,2,27]],"date-time":"2007-02-27T22:39:54Z","timestamp":1172615994000},"page":"1021-1028","source":"Crossref","is-referenced-by-count":188,"title":["Pharmacokinetics and pharmacodynamics of intravenous PEGylated recombinant mammalian urate oxidase in patients with refractory gout"],"prefix":"10.1002","volume":"56","author":[{"given":"John S.","family":"Sundy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy J.","family":"Ganson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan J.","family":"Kelly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edna 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