Duke Clinical Research Unit, Duke University Medical Center, Durham, North Carolina, USA.
JAMA. 2011 Aug 17;306(7):711-20. doi: 10.1001/jama.2011.1169.
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.
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.
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).
Primary end point was plasma uric acid levels of less than 6.0 mg/dL in months 3 and 6.
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 < .001 and <.04 for comparisons between biweekly and monthly groups vs placebo, respectively). Among patients treated with pegloticase in trial C0406, 16 of 42 in the biweekly group (38%; 95% CI, 24%-54%) and 21 of 43 in the monthly group (49%; 95% CI, 33%-65%) achieved the primary end point; no placebo-treated patients reached the primary end point (0/23; 95% CI, 0%-15%; P = .001 and < .001, respectively). When data in the 2 trials were pooled, the primary end point was achieved in 36 of 85 patients in the biweekly group (42%; 95% CI, 32%-54%), 29 of 84 patients in the monthly group (35%; 95% CI, 24%-46%), and 0 of 43 patients in the placebo group (0%; 95% CI, 0%-8%; P < .001 for each comparison). Seven deaths (4 in patients receiving pegloticase and 3 in the placebo group) occurred between randomization and closure of the study database (February 15, 2008).
Among patients with chronic gout, elevated serum uric acid level, and allopurinol intolerance or refractoriness, the use of pegloticase 8 mg either every 2 weeks or every 4 weeks for 6 months resulted in lower uric acid levels compared with placebo.
clinicaltrials.gov Identifier: NCT00325195.
需要及时治疗以控制与组织尿酸盐晶体沉积相关的疾病表现的慢性致残性痛风患者，需要进行常规降尿酸治疗。聚乙二醇化尿酸酶是一种单甲氧基聚乙二醇结合的哺乳动物重组尿酸酶，用于满足这一需求。
评估聚乙二醇尿酸酶治疗难治性慢性痛风的疗效和耐受性。
设计、地点和患者：2006 年 6 月至 2007 年 10 月期间，在美国、加拿大和墨西哥的 56 个风湿病诊所进行了两项复制、随机、双盲、安慰剂对照试验（C0405 和 C0406），入组了患有严重痛风、别嘌呤醇不耐受或难治性疾病以及血清尿酸浓度为 8.0mg/dL 或更高的患者。共有 225 名患者参与：试验 C0405 中 109 名，试验 C0406 中 116 名。
每两周静脉输注 12 次，每次输注含 8mg 聚乙二醇尿酸酶（每周两次治疗组）、连续输注时聚乙二醇尿酸酶与安慰剂交替（每月治疗组）或安慰剂（安慰剂组）。
主要终点是第 3 个月和第 6 个月时血浆尿酸水平<6.0mg/dL。
在试验 C0405 中，每周两次治疗组的主要终点达到 43 例患者中的 20 例（47%；95%CI，31%-62%）、每月治疗组的 41 例患者中的 8 例（20%；95%CI，9%-35%）和安慰剂组的 0 例患者（0%；95%CI，0%-17%；与每月治疗组和安慰剂组相比，P<0.001 和<0.04）。在试验 C0406 中接受聚乙二醇尿酸酶治疗的患者中，每周两次治疗组的 42 例患者中的 16 例（38%；95%CI，24%-54%）和每月治疗组的 43 例患者中的 21 例（49%；95%CI，33%-65%）达到了主要终点；安慰剂治疗组无患者达到主要终点（0/23；95%CI，0%-15%；P=0.001 和<0.001）。当合并两项试验的数据时，每周两次治疗组的 85 例患者中有 36 例（42%；95%CI，32%-54%）、每月治疗组的 84 例患者中有 29 例（35%；95%CI，24%-46%）和安慰剂组的 43 例患者中 0 例（0%；95%CI，0%-8%；与安慰剂相比，P<0.001）达到了主要终点。7 例死亡（聚乙二醇尿酸酶治疗组 4 例，安慰剂组 3 例）发生在随机分组至研究数据库关闭期间（2008 年 2 月 15 日）。
在慢性痛风、血清尿酸水平升高和别嘌呤醇不耐受或难治的患者中，与安慰剂相比，每 2 周或每 4 周使用 8mg 聚乙二醇尿酸酶治疗 6 个月可降低尿酸水平。
临床试验.gov 标识符：NCT00325195。
