Becker Michael A, Schumacher H Ralph, Wortmann Robert L, MacDonald Patricia A, Eustace Denise, Palo William A, Streit Janet, Joseph-Ridge Nancy
University of Chicago Pritzker School of Medicine, Chicago, USA.
N Engl J Med. 2005 Dec 8;353(23):2450-61. doi: 10.1056/NEJMoa050373.
Febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase, is a potential alternative to allopurinol for patients with hyperuricemia and gout.
We randomly assigned 762 patients with gout and with serum urate concentrations of at least 8.0 mg per deciliter (480 micromol per liter) to receive either febuxostat (80 mg or 120 mg) or allopurinol (300 mg) once daily for 52 weeks; 760 received the study drug. Prophylaxis against gout flares with naproxen or colchicine was provided during weeks 1 through 8. The primary end point was a serum urate concentration of less than 6.0 mg per deciliter (360 micromol per liter) at the last three monthly measurements. The secondary end points included reduction in the incidence of gout flares and in tophus area.
The primary end point was reached in 53 percent of patients receiving 80 mg of febuxostat, 62 percent of those receiving 120 mg of febuxostat, and 21 percent of those receiving allopurinol (P<0.001 for the comparison of each febuxostat group with the allopurinol group). Although the incidence of gout flares diminished with continued treatment, the overall incidence during weeks 9 through 52 was similar in all groups: 64 percent of patients receiving 80 mg of febuxostat, 70 percent of those receiving 120 mg of febuxostat, and 64 percent of those receiving allopurinol (P=0.99 for 80 mg of febuxostat vs. allopurinol; P=0.23 for 120 mg of febuxostat vs. allopurinol). The median reduction in tophus area was 83 percent in patients receiving 80 mg of febuxostat and 66 percent in those receiving 120 mg of febuxostat, as compared with 50 percent in those receiving allopurinol (P=0.08 for 80 mg of febuxostat vs. allopurinol; P=0.16 for 120 mg of febuxostat vs. allopurinol). More patients in the high-dose febuxostat group than in the allopurinol group (P=0.003) or the low-dose febuxostat group discontinued the study. Four of the 507 patients in the two febuxostat groups (0.8 percent) and none of the 253 patients in the allopurinol group died; all deaths were from causes that the investigators (while still blinded to treatment) judged to be unrelated to the study drugs (P=0.31 for the comparison between the combined febuxostat groups and the allopurinol group).
Febuxostat, at a daily dose of 80 mg or 120 mg, was more effective than allopurinol at the commonly used fixed daily dose of 300 mg in lowering serum urate. Similar reductions in gout flares and tophus area occurred in all treatment groups.
非布司他是一种新型的非嘌呤类黄嘌呤氧化酶选择性抑制剂，对于高尿酸血症和痛风患者而言，它是别嘌醇的一种潜在替代药物。
我们将762例痛风患者且血清尿酸盐浓度至少为每分升8.0毫克（480微摩尔/升）的患者随机分组，分别给予非布司他（80毫克或120毫克）或别嘌醇（300毫克），每日一次，持续52周；760例患者接受了研究药物治疗。在第1周至第8周期间，采用萘普生或秋水仙碱预防痛风发作。主要终点是在最后三次每月测量时血清尿酸盐浓度低于每分升6.0毫克（360微摩尔/升）。次要终点包括痛风发作次数的减少和痛风石面积的缩小。
接受80毫克非布司他的患者中有53%达到主要终点，接受120毫克非布司他的患者中有62%达到主要终点，接受别嘌醇的患者中有21%达到主要终点（各非布司他组与别嘌醇组比较，P<0.001）。尽管随着持续治疗痛风发作的发生率有所降低，但在第9周至第52周期间所有组的总体发生率相似：接受80毫克非布司他的患者中有64%，接受120毫克非布司他的患者中有70%，接受别嘌醇的患者中有64%（80毫克非布司他与别嘌醇比较，P = 0.99；120毫克非布司他与别嘌醇比较，P = 0.23）。接受80毫克非布司他的患者痛风石面积的中位数减少了83%，接受120毫克非布司他的患者减少了66%，而接受别嘌醇的患者减少了5%（80毫克非布司他与别嘌醇比较，P = 0.08；120毫克非布司他与别嘌醇比较，P = 0.16）。高剂量非布司他组中停止研究的患者比别嘌醇组（P = 0.003）或低剂量非布司他组更多。两个非布司他组的507例患者中有4例（0.8%）死亡，别嘌醇组的253例患者中无死亡；所有死亡原因经研究者（仍对治疗不知情）判断与研究药物无关（联合非布司他组与别嘌醇组比较，P = 0.31）。
每日剂量为80毫克或120毫克的非布司他在降低血清尿酸方面比常用的每日固定剂量300毫克的别嘌醇更有效。所有治疗组痛风发作次数和痛风石面积的减少相似。
