Tausche Anne-Kathrin, Alten Rieke, Dalbeth Nicola, Kopicko Jeff, Fung Maple, Adler Scott, Bhakta Nihar, Storgard Chris, Baumgartner Scott, Saag Kenneth
Department of Rheumatology, Technical University Dresden, Dresden.
Department of Internal Medicine II, University Medicine Berlin, Berlin, Germany.
Rheumatology (Oxford). 2017 Dec 1;56(12):2170-2178. doi: 10.1093/rheumatology/kex350.
To investigate the efficacy and safety of lesinurad, a selective uric acid reabsorption inhibitor, in a 6 month, phase 3 clinical trial and extension study.
Patients with gout who cannot take a xanthine oxidase inhibitor (XOI) and have serum uric acid (sUA) ⩾6.5 mg/dl were randomized to receive oral lesinurad (400 mg daily) or placebo. The primary endpoint was the proportion of patients with sUA <6.0 mg/dl at month 6. Safety assessments included treatment-emergent adverse events (TEAEs) and laboratory data. Patients who completed the study were eligible for an open-label, uncontrolled extension study of lesinurad 400 mg monotherapy.
Patients (n = 214) were primarily white males (mean age 54.4 years; gout duration 11.2 years). Significantly more patients achieved the primary endpoint with lesinurad than placebo (29.9 vs 1.9%; P < 0.0001). Overall TEAE rates were higher with lesinurad (77.6 vs 65.4%); renal-related TEAEs (17.8%), renal-related serious TEAEs (4.7%) and serum creatinine elevations (1.5 times baseline, 24.3%) occurred only with lesinurad. A total of 143 patients (65 lesinurad, 78 placebo) enrolled in the extension study. Treatment with lesinurad 400 mg resulted in rapid and sustained sUA lowering that persisted for up to 18 months before the study was terminated prematurely. No new safety findings were observed in the extension.
In patients with gout and intolerance/contraindication to XOIs, lesinurad 400 mg monotherapy demonstrated superior sUA lowering compared with placebo, with sustained effects for up to 18 months. Due to a high incidence of serum creatinine elevations and renal-related adverse events, including serious adverse events with lesinurad 400 mg, lesinurad should not be used as monotherapy.
ClinicalTrials.gov (http://clinincaltrials.gov), NCT01508702.
在一项为期6个月的3期临床试验及扩展研究中，调查选择性尿酸重吸收抑制剂雷西纳德的疗效和安全性。
无法服用黄嘌呤氧化酶抑制剂（XOI）且血清尿酸（sUA）⩾6.5mg/dl的痛风患者被随机分组，接受口服雷西纳德（每日400mg）或安慰剂。主要终点为第6个月时sUA<6.0mg/dl的患者比例。安全性评估包括治疗中出现的不良事件（TEAE）和实验室数据。完成研究的患者有资格参加雷西纳德400mg单药治疗的开放标签、非对照扩展研究。
患者（n = 214）主要为白人男性（平均年龄54.4岁；痛风病程11.2年）。与安慰剂相比，使用雷西纳德达到主要终点的患者显著更多（29.9%对1.9%；P<0.0001）。雷西纳德的总体TEAE发生率更高（77.6%对65.4%）；仅雷西纳德出现了与肾相关的TEAE（17.8%）、与肾相关的严重TEAE（4.7%）和血清肌酐升高（高于基线1.5倍，24.3%）。共有143名患者（65名雷西纳德组，78名安慰剂组）参加了扩展研究。使用400mg雷西纳德治疗可使sUA迅速且持续降低，在研究提前终止前这种降低持续了长达18个月。扩展研究中未观察到新的安全性发现。
在对XOIs不耐受/有禁忌的痛风患者中，400mg雷西纳德单药治疗在降低sUA方面优于安慰剂，且效果可持续长达18个月。由于血清肌酐升高及与肾相关不良事件的发生率较高，包括400mg雷西纳德所致的严重不良事件，雷西纳德不应作为单药使用。
ClinicalTrials.gov（http://clinincaltrials.gov），NCT01508702
