Efficacy and Tolerability of Pegloticase for the Treatment of Chronic Gout in Patients Refractory to Conventional Treatment Two Randomized Controlled Trials
Efficacy and Tolerability of Pegloticase for the Treatment of Chronic Gout in Patients Refractory to Conventional Treatment Two Randomized Controlled Trials
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DOI：
10.1001/jama.2011.116
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发表时间：
2011-08-17
影响因子：
120.7
通讯作者：
Becker, Michael A.
中科院分区：
文献类型：
--
作者：
Sundy, John S.;Baraf, Herbert S. B.;Becker, Michael A.
背景慢性致残性痛风对常规降尿酸治疗无效，需及时治疗以控制组织尿酸结晶沉积相关疾病表现。Pegloticase是一种单甲氧基聚乙二醇偶联的哺乳动物重组尿酸酶，正是为了满足这一需求而开发的。目的评价pegloticase治疗难治性慢性痛风的疗效和耐受性。设计、环境和患者2006年6月至2007年10月，在美国、加拿大和墨西哥的56个风湿病诊所进行了两项重复、随机、双盲、安慰剂对照试验（C0405和C0406），研究对象为严重痛风、别嘌呤醇不耐受或难耐、血清尿酸浓度为8.0 mg/dL或更高的患者。共有225例患者参与：109例试验C0405, 116例试验C0406。干预措施每两周静脉输注12次，每次输注含pegloticase 8mg（两周治疗组），连续输注pegloticase与安慰剂交替输注（每月治疗组）或安慰剂（安慰剂组）。主要终点为第3和6个月血浆尿酸水平低于6.0 mg/dL。在C0405试验中，两周治疗组43例患者中有20例达到主要终点（47%,95% CI, 31%-62%），每月治疗组41例患者中有8例（20%,95% CI, 9%-35%），安慰剂治疗组0例患者（0/20,95% CI, 0%-17%）达到主要终点
Context Patients with chronic disabling gout refractory to conventional urate-lowering therapy need timely treatment to control disease manifestations related to tissue urate crystal deposition. Pegloticase, monomethoxypoly(ethylene glycol)-conjugated mammalian recombinant uricase, was developed to fulfill this need.Objective To assess the efficacy and tolerability of pegloticase in managing refractory chronic gout.Design, Setting, and Patients Two replicate, randomized, double-blind, placebo-controlled trials (C0405 and C0406) were conducted between June 2006 and October 2007 at 56 rheumatology practices in the United States, Canada, and Mexico in patients with severe gout, allopurinol intolerance or refractoriness, and serum uric acid concentration of 8.0 mg/dL or greater. A total of 225 patients participated: 109 in trial C0405 and 116 in trial C0406.Intervention Twelve biweekly intravenous infusions containing either pegloticase 8 mg at each infusion (biweekly treatment group), pegloticase alternating with placebo at successive infusions (monthly treatment group), or placebo (placebo group).Main Outcome Measure Primary end point was plasma uric acid levels of less than 6.0 mg/dL in months 3 and 6.Results In trial C0405 the primary end point was reached in 20 of 43 patients in the biweekly group (47%; 95% CI, 31%-62%), 8 of 41 patients in the monthly group (20%; 95% CI, 9%-35%), and in 0 patients treated with placebo (0/20; 95% CI, 0%-17%; P