University of Alabama at Birmingham.
East-West Medical Research Institute, Honolulu, Hawaii.
Arthritis Rheumatol. 2017 Jan;69(1):203-212. doi: 10.1002/art.39840.
Lesinurad is a selective uric acid reabsorption inhibitor used for the treatment of gout in combination with a xanthine oxidase inhibitor. The Combining Lesinurad with Allopurinol Standard of Care in Inadequate Responders (CLEAR 1) study, a 12-month, multicenter, randomized, double-blind, placebo-controlled phase III trial, was conducted to investigate daily lesinurad (200 mg or 400 mg orally) added to allopurinol versus placebo plus allopurinol in patients with serum urate (UA) levels above a target of <6.0 mg/dl.
Patients receiving ≥300 mg of allopurinol (≥200 mg in those with moderate renal impairment) who had serum UA levels ≥6.5 mg/dl at screening and ≥2 gout flares during the previous year were studied. The primary end point was the proportion of patients achieving a serum UA level of <6.0 mg/dl at month 6. Key secondary end points were the mean gout flare rate requiring treatment (months 7-12) and the proportions of patients with complete resolution of ≥1 target tophus (month 12). Safety assessments included adverse events and laboratory data.
The study patients (n = 603) were predominantly male and had a mean ± SD age of 51.9 ± 11.3 years, a gout duration of 11.8 ± 9.4 years, a baseline serum UA level of 6.94 ± 1.27 mg/dl, and were receiving an allopurinol dosage of 306.6 ± 59.58 mg/day. Lesinurad at doses of 200 mg or 400 mg added to allopurinol therapy significantly increased the proportions of patients who achieved serum UA target levels by month 6 as compared with those receiving allopurinol alone (54.2%, 59.2%, and 27.9%, respectively, P < 0.0001). Lesinurad was not significantly superior to allopurinol alone in terms of the secondary end points: rates of gout flares and complete resolution of tophi. Lesinurad was generally well-tolerated; the safety profile of the 200-mg dose was comparable to that of allopurinol alone, except for higher incidences of predominantly reversible elevations of serum creatinine levels.
Lesinurad added to allopurinol provided benefit as compared with allopurinol alone in reducing serum UA levels and represents a new treatment option for patients needing additional urate-lowering therapy.
Lesinurad 是一种选择性尿酸重吸收抑制剂，用于与黄嘌呤氧化酶抑制剂联合治疗痛风。在血清尿酸（UA）水平高于目标值<6.0mg/dl 的患者中，进行了为期 12 个月、多中心、随机、双盲、安慰剂对照的 III 期临床试验，即联合 Lesinurad 与别嘌醇标准治疗在不充分应答者中的研究（CLEAR 1），以评估每日 Lesinurad（200mg 或 400mg 口服）加别嘌醇与安慰剂加别嘌醇相比的疗效。
研究纳入了正在接受≥300mg 别嘌醇（中度肾功能不全者≥200mg）治疗、筛选时血清 UA 水平≥6.5mg/dl 且在前一年有≥2 次痛风发作的患者。主要终点是在第 6 个月时达到血清 UA 水平<6.0mg/dl 的患者比例。次要关键终点是治疗期间需要治疗的痛风发作平均率（第 7-12 个月）和完全缓解≥1 个目标痛风石的患者比例（第 12 个月）。安全性评估包括不良事件和实验室数据。
研究患者（n=603）主要为男性，平均年龄为 51.9±11.3 岁，痛风病程为 11.8±9.4 年，基线血清 UA 水平为 6.94±1.27mg/dl，正在接受 306.6±59.58mg/dl 的别嘌醇剂量治疗。与单独使用别嘌醇相比，Lesinurad 200mg 和 400mg 剂量分别显著增加了在第 6 个月达到血清 UA 目标水平的患者比例（分别为 54.2%、59.2%和 27.9%，P<0.0001）。在次要终点方面，Lesinurad 与单独使用别嘌醇相比并没有显著优势：痛风发作率和痛风石完全缓解率。Lesinurad 总体耐受性良好；200mg 剂量的安全性与单独使用别嘌醇相当，除了血清肌酐水平升高的发生率较高且主要为可逆外。
与单独使用别嘌醇相比，Lesinurad 加用别嘌醇可降低血清 UA 水平，为需要额外降尿酸治疗的患者提供了一种新的治疗选择。
