Castrejon Isabel, Toledano Esther, Rosario María Piedad, Loza Estíbaliz, Pérez-Ruiz Fernando, Carmona Loreto
Division of Rheumatology, Rush University Medical Center, 1611 West Harrison Street, Suite 510, Chicago, IL, 60612, USA,
Rheumatol Int. 2015 Jul;35(7):1127-37. doi: 10.1007/s00296-014-3189-6. Epub 2014 Dec 18.
Allopurinol is the most widely used urate-lowering drug (ULD). Together with efficacy and cost, safety is an aspect that helps taking clinical decisions. This systematic review analyzes allopurinol safety. The literature search was performed in MEDLINE, EMBASE, and the Cochrane Library (January 2014).
(a) patients >18, (b) gout by the ACR criteria or evidence of urate crystal in synovial fluid, (c) comparator (placebo or other ULD), and (d) RCTs, cohorts, or meta-analysis.
rate of adverse events and death. The quality was assessed with the Jadad's scale. A meta-analysis with fixed effects was performed. From 544 studies, seven met the eligibility criteria and were included. All RCT presented a low power for safety. All RCTs included a mixed population of patients with gout and hyperuricemia. Allopurinol (300 mg) was compared to febuxostat (40-240 mg) in five RCTs, to benzbromarone and probenecid in two RCTs, and to placebo in one. In the RCTs comparing allopurinol with benzbromarone and probenecid, the highest discontinuation rate was with probenecid (26 %), followed by allopurinol (11 %) and benzbromarone (4 %). The incidence of adverse events was similar between allopurinol (range 38.6-85) and febuxostat (range 41.8-80). Six patients on febuxostat and three on allopurinol died during the studies; no deaths were judged related to drug. The combined risk of adverse events was RR = 1.04 (95 % CI 0.98, 1.11). Allopurinol is a safe option, slightly better than other ULDs. The grade of evidence is high, but further research is needed to evaluate higher doses and long-term safety.
别嘌醇是使用最广泛的降尿酸药物（ULD）。除疗效和成本外，安全性也是辅助临床决策的一个方面。本系统评价分析别嘌醇的安全性。于2014年1月在MEDLINE、EMBASE和Cochrane图书馆进行文献检索。
（a）患者年龄>18岁；（b）符合美国风湿病学会（ACR）标准的痛风或滑液中有尿酸盐结晶的证据；（c）对照（安慰剂或其他ULD）；（d）随机对照试验（RCT）、队列研究或荟萃分析。
不良事件发生率和死亡率。采用Jadad量表评估质量。进行了固定效应荟萃分析。从544项研究中，7项符合纳入标准并被纳入。所有RCT安全性检验效能均较低。所有RCT纳入的患者群体均为痛风和高尿酸血症患者的混合群体。在5项RCT中，将别嘌醇（300毫克）与非布司他（40 - 240毫克）进行比较，在2项RCT中与苯溴马隆和丙磺舒进行比较，在1项RCT中与安慰剂进行比较。在比较别嘌醇与苯溴马隆和丙磺舒的RCT中，停药率最高的是丙磺舒（26%），其次是别嘌醇（11%）和苯溴马隆（4%）。别嘌醇（范围38.6 - 85）和非布司他（范围41.8 - 80）之间不良事件发生率相似。研究期间，6例使用非布司他的患者和3例使用别嘌醇的患者死亡；未判定有死亡与药物相关。不良事件的合并风险为RR = 1.04（95%CI 0.98，1.11）。别嘌醇是一种安全的选择，略优于其他ULD。证据等级高，但需要进一步研究以评估更高剂量和长期安全性。
