Baseline urate level and renal function predict outcomes of urate-lowering therapy using low doses of febuxostat and benzbromarone: a prospective, randomized controlled study in a Chinese primary gout cohort
Baseline urate level and renal function predict outcomes of urate-lowering therapy using low doses of febuxostat and benzbromarone: a prospective, randomized controlled study in a Chinese primary gout cohort
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基线尿酸水平和肾功能预测使用低剂量非布索坦和苯溴马隆降尿酸治疗的结果：一项针对中国原发性痛风队列的前瞻性、随机对照研究
DOI：
10.1186/s13075-019-1976-x
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发表时间：
2019-09-02
影响因子：
4.9
通讯作者：
Li, Changgui
中科院分区：
文献类型：
--
作者：
Liang, Nan;Sun, Mingshu;Li, Changgui
背景低剂量非布司他或苯溴马隆在亚洲国家广泛使用，但缺乏研究来比较这两种降尿酸药物的疗效和安全性。在中国一家专门的痛风诊所，在原发性痛风男性患者中进行了一项开放标签试验，用于降低尿酸盐治疗（AUG）。由第三方机构根据随机数字表进行随机化。将患者按1：1随机分为非布司他组（Feb组）和苯溴马隆组（Ben组），分别给予非布司他20 mg/d和苯溴马隆25 mg/d，治疗12周。在基线和每月每次访视时收集一般信息和生化数据。结果两组患者共240例，其中214例完成了12周的随访，其中Feb组105例，Ben组109例。12周后，Feb组和Ben组均有相当比例的患者达到目标血清尿酸（sUA）（< 360 μmol/L），两组的血清尿酸水平均显著降低（Feb组为39.5%和156.83 μmol/L，Ben组为35.7%和163.99 μmol/L）。多因素分析表明，基线sUA水平和肾功能与达到目标sUA（RAT）率的结局相关。亚组分析表明，对于基线时sUA < 540 μmol/L且肌酐清除率（Ccr）≤ 110 mL min−11.73 m− 2的患者，低剂量非布司他和苯溴马隆可提供更好的RAT。结论非布司他20 mg/d和苯溴马隆25 mg/d均能降低sUA水平，且基线时sUA水平< 540 μmol/L或Ccr ≤ 110 mL min-11.73 m-2的痛风患者有更好的机会达到目标尿酸水平。目前的研究表明，sUA水平和肾功能是向痛风患者推荐低剂量非布司他和苯溴马隆时要考虑的关键因素。 ChiCTR 1800019352 （追溯登记）。
BackgroundLow doses of febuxostat or benzbromarone are widely used in Asian countries, but lacking studies to compare the efficacy and safety of the two urate-lowering drugs.MethodsTo compare the efficacy and safety of low-dose febuxostat with low-dose benzbromarone in patients with primary gout, a randomized controlled, open-label trial was performed among male patients with primary gout for urate-lowering therapy (ULT) in a dedicated gout clinic in China. Randomization was carried out by a third-party institution according to random number table. Patients were randomly assigned 1:1 to febuxostat group (Feb group) (20 mg daily) or benzbromarone group (Ben group) (25 mg daily) and treated for 12 weeks. General information and biochemical data were collected at baseline and at every visit monthly. Clinical characteristics before and after the ULT were analyzed in the two groups by SPSS and EmpowerStats software.ResultsTwo hundred forty patients were enrolled and randomized in the two groups, with 214 patients completing 12 weeks’ ULT (105 in the Feb group and 109 in the Ben group). After 12 weeks, substantial percentages of patients in both Feb and Ben group achieved the target serum uric acid (sUA) (< 360 μmol/L) and serum urate levels were reduced significantly for both groups (Feb 39.5% and 156.83 μmol/L vs. Ben 35.7% and 163.99 μmol/L). Multivariate analysis suggests baseline sUA level and renal function were associated with the outcome of the rate of achieving target sUA (RAT). Sub-group analysis suggests low doses of febuxostat and benzbromarone rendered better RAT for patients with sUA < 540 μmol/L and creatinine clearance rate (Ccr) ≤ 110 mL min−11.73 m−2at baseline. The drugs were well tolerated, and the incidence of gout flares in Feb group was similar with that in Ben group (22.85% vs. 33.94%).ConclusionOverall, febuxostat 20 mg daily and benzbromarone 25 mg daily reduced sUA, and gout patients with sUA level < 540 μmol/L or Ccr ≤ 110 mL min−11.73 m−2at baseline had better chance to achieve target uric acid levels. The current study suggests sUA level and renal function are key factors to consider when recommending low doses of febuxostat and benzbromarone to gout patients.Trial registrationRegistered with ChiCTR, No. ChiCTR1800019352 (retrospectively registered).