Fan Meida, Liu Jian, Zhao Bingcheng, Wu Xinyu, Li Xuefeng, Gu Jieruo, Schlesinger Naomi
Department of Rheumatology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People's Republic of China.
Department of Rheumatology, The Third Affiliated Hospital of Sun Yat-sen University, 600 Tianhe Road, Tianhe, Guangzhou, 510630, People's Republic of China.
Clin Rheumatol. 2021 Feb;40(2):683-692. doi: 10.1007/s10067-020-05272-4. Epub 2020 Jul 11.
To assess the efficacy and safety of the commonly used urate-lowering therapies (ULTs): febuxostat, allopurinol, and lesinurad in hyperuricemic patients with gout.
We included all randomized controlled trials (RCTs) that compared ULTs with placebo or head to head. The primary efficacy endpoint was the proportion of subjects achieving the target serum urate (SU) level at month 6. Safety outcomes included total adverse events (AEs), serious AEs, withdrawals due to AEs, and AEs per organ system. A Bayesian network model was used to compare all ULTs with placebo and among themselves.
Fifteen RCTs were included for the analysis, in which 7968 patients were randomly assigned to take either placebo or one of 11 ULTs: allopurinol, febuxostat 40/80/120/240 mg/day, lesinurad 400 mg/day, lesinurad 200/400/600 mg/day plus allopurinol, and lesinurad 200/400 mg/day plus febuxostat. All ULTs were effective in achieving the target SU level at month 6 compared with placebo (ORs between 26.81 and 1928). Febuxostat 80/120/240 mg/day was superior to allopurinol and well tolerated for urate reduction. And as febuxostat dosage increased, more patients achieved the target SU level. Furthermore, the lesinurad combination with xanthine oxidase inhibitor (XOI) groups had a higher proportion of patients achieving the target SU level than the febuxostat 40 mg/day group (ORs between 2.89 and 9.17), the allopurinol group (ORs between 3.56 and 11.27), or the lesinurad 400 mg/day monotherapy group (ORs between 12.30 and 39.17) but might have a high risk of AEs.
All ULTs are effective in achieving the target SU level compared with placebo in hyperuricemic patients with gout. Lesinurad in combination with febuxostat or allopurinol is effective in urate lowering, especially for patients with inadequate response to XOI monotherapy. Key Points • All urate-lowering therapies (ULTs) were effective in achieving the target serum urate (SU) level at month 6 compared with placebo in hyperuricemic patients with gout. • Febuxostat 80/120/240 mg/day was superior to allopurinol and well tolerated for urate reduction. And as febuxostat dosage increased, more patients achieved the target SU level. • Lesinurad in combination with febuxostat or allopurinol was effective in urate lowering, especially for patients with inadequate response to xanthine oxidase inhibitor monotherapy, but might have a high risk of AEs.
评估常用降尿酸治疗（ULTs）药物非布司他、别嘌醇和雷西纳德在痛风高尿酸血症患者中的疗效和安全性。
我们纳入了所有将ULTs与安慰剂进行比较或ULTs之间进行头对头比较的随机对照试验（RCTs）。主要疗效终点是在第6个月达到目标血清尿酸（SU）水平的受试者比例。安全性指标包括总不良事件（AEs）、严重不良事件、因不良事件导致的撤药以及各器官系统的不良事件。使用贝叶斯网络模型对所有ULTs与安慰剂以及ULTs之间进行比较。
纳入15项RCTs进行分析，其中7968例患者被随机分配服用安慰剂或11种ULTs之一：别嘌醇、40/80/120/240mg/天的非布司他、400mg/天的雷西纳德、200/400/600mg/天雷西纳德加别嘌醇以及200/400mg/天雷西纳德加非布司他。与安慰剂相比，所有ULTs在第6个月达到目标SU水平方面均有效（比值比在26.81至1928之间）。80/120/240mg/天的非布司他优于别嘌醇，且降尿酸耐受性良好。并且随着非布司他剂量增加，更多患者达到目标SU水平。此外，雷西纳德与黄嘌呤氧化酶抑制剂（XOI）联合治疗组达到目标SU水平的患者比例高于40mg/天非布司他组（比值比在2.89至9.17之间）、别嘌醇组（比值比在3.56至11.27之间）或400mg/天雷西纳德单药治疗组（比值比在12.30至39.17之间），但可能有较高的不良事件风险。
与安慰剂相比，所有ULTs在痛风高尿酸血症患者中实现目标SU水平方面均有效。雷西纳德与非布司他或别嘌醇联合使用在降低尿酸方面有效，特别是对于XOI单药治疗反应不佳的患者。要点：•与安慰剂相比，所有降尿酸治疗（ULTs）在痛风高尿酸血症患者第6个月时实现目标血清尿酸（SU）水平方面均有效。•80/120/240mg/天的非布司他优于别嘌醇，且降尿酸耐受性良好。并且随着非布司他剂量增加，更多患者达到目标SU水平。•雷西纳德与非布司他或别嘌醇联合使用在降低尿酸方面有效，特别是对于黄嘌呤氧化酶抑制剂单药治疗反应不佳的患者，但可能有较高的不良事件风险。
