Abstract：
OBJECTIVE: We systematically examined comparative gout flare risk after initiation or escalation of different urate-lowering therapies (ULTs), comparative flare risk with and without concomitant flare prophylaxis, adverse event rates associated with flare prophylaxis, and optimal duration of flare prophylaxis.
METHODS: We searched the Medline, Embase, Web of Science, and Cochrane databases and clinical trial registries from inception to November 2021 for trials investigating adults with gout initiating or escalating ULT. We performed random effects network meta-analyses and calculated risk ratios (RRs) between treatments. Bias was assessed using the revised Cochrane risk-of-bias tool.
RESULTS: We identified 3,775 records, of which 29 publications (27 trials) were included. When compared to placebo plus prophylaxis, the RR of flares ranged from 1.08 (95% confidence interval [CI] 0.87-1.33) for febuxostat 40 mg plus prophylaxis to RR 2.65 [95% CI 1.58-4.45] for febuxostat 80 mg plus lesinurad 400 mg plus prophylaxis. Compared to ULT alone, the RR of flares was lower for ULT plus rilonacept 160 mg (RR 0.35 [95% CI 0.25-0.50]), ULT plus rilonacept 80 mg (RR 0.43 [95% CI 0.31-0.60]) and ULT plus colchicine (RR 0.50 [95% CI 0.35-0.72]). There was limited evidence for other flare prophylaxis and on prophylaxis harms and optimal duration. Primarily because of missing outcome data and bias in the selection of reported results, 71.4% and 63.4% of studies were assessed as high risk of bias for flares and adverse events, respectively.
CONCLUSIONS: The RR of flares when introducing ULT varies depending on ULT drug and dosing strategies. There were limited data on ULT escalation. Flare prophylaxis with colchicine and rilonacept reduces flare incidence. More research is required on the harms and optimal duration of prophylaxis.
METHODS: We searched the Medline, Embase, Web of Science, and Cochrane databases and clinical trial registries from inception to November 2021 for trials investigating adults with gout initiating or escalating ULT. We performed random effects network meta-analyses and calculated risk ratios (RRs) between treatments. Bias was assessed using the revised Cochrane risk-of-bias tool.
RESULTS: We identified 3,775 records, of which 29 publications (27 trials) were included. When compared to placebo plus prophylaxis, the RR of flares ranged from 1.08 (95% confidence interval [CI] 0.87-1.33) for febuxostat 40 mg plus prophylaxis to RR 2.65 [95% CI 1.58-4.45] for febuxostat 80 mg plus lesinurad 400 mg plus prophylaxis. Compared to ULT alone, the RR of flares was lower for ULT plus rilonacept 160 mg (RR 0.35 [95% CI 0.25-0.50]), ULT plus rilonacept 80 mg (RR 0.43 [95% CI 0.31-0.60]) and ULT plus colchicine (RR 0.50 [95% CI 0.35-0.72]). There was limited evidence for other flare prophylaxis and on prophylaxis harms and optimal duration. Primarily because of missing outcome data and bias in the selection of reported results, 71.4% and 63.4% of studies were assessed as high risk of bias for flares and adverse events, respectively.
CONCLUSIONS: The RR of flares when introducing ULT varies depending on ULT drug and dosing strategies. There were limited data on ULT escalation. Flare prophylaxis with colchicine and rilonacept reduces flare incidence. More research is required on the harms and optimal duration of prophylaxis.
摘要：
目的：系统检查：不同降尿酸治疗（ULT）开始或升级后的比较耀斑风险；有和没有伴随耀斑预防的比较耀斑风险；与耀斑预防相关的不良事件发生率；以及耀斑预防的最佳持续时间。
方法：我们搜索了Medline，Embase,WebofScience,Cochrane数据库和临床试验注册中心从开始到2021年11月，用于调查患有痛风的成年人开始或升级的ULT。我们进行了随机效应网络荟萃分析，并计算了治疗之间的风险比（RR）。使用修订的Cochrane偏倚风险工具评估偏倚。
结果：我们确定了3775条记录，其中29篇出版物(27项试验)被纳入.与安慰剂+预防相比，耀斑的RR范围为:非布索坦40mg+预防的1·08[95%置信区间(95%CI)0·87-1·33],非布索坦80mg+lesinurad400mg+预防的2·65[95%CI1·58-4·45]。与ULT相比，ULT+rilonacept160mg的耀斑RR较低(RR=0·35[95%CI0·25-0·50])，ULT+利洛纳80mg(RR=0·43[95%CI0·31-0·60])和ULT+秋水仙碱(RR=0·50[95%CI0·35-0·72])。其他预防耀斑的证据有限，以及预防危害和最佳持续时间。主要由于缺少结果数据和选择报告结果的偏差，分别有71·4％和63·4％的研究被评估为耀斑和不良事件的高偏倚风险。
结论：引入ULT时发生耀斑的相对风险因ULT药物和给药策略而异。关于ULT升级的数据有限。用秋水仙碱和利洛沙普预防耀斑可降低耀斑发生率。需要对预防的危害和最佳持续时间进行更多研究。
方法：我们搜索了Medline，Embase,WebofScience,Cochrane数据库和临床试验注册中心从开始到2021年11月，用于调查患有痛风的成年人开始或升级的ULT。我们进行了随机效应网络荟萃分析，并计算了治疗之间的风险比（RR）。使用修订的Cochrane偏倚风险工具评估偏倚。
结果：我们确定了3775条记录，其中29篇出版物(27项试验)被纳入.与安慰剂+预防相比，耀斑的RR范围为:非布索坦40mg+预防的1·08[95%置信区间(95%CI)0·87-1·33],非布索坦80mg+lesinurad400mg+预防的2·65[95%CI1·58-4·45]。与ULT相比，ULT+rilonacept160mg的耀斑RR较低(RR=0·35[95%CI0·25-0·50])，ULT+利洛纳80mg(RR=0·43[95%CI0·31-0·60])和ULT+秋水仙碱(RR=0·50[95%CI0·35-0·72])。其他预防耀斑的证据有限，以及预防危害和最佳持续时间。主要由于缺少结果数据和选择报告结果的偏差，分别有71·4％和63·4％的研究被评估为耀斑和不良事件的高偏倚风险。
结论：引入ULT时发生耀斑的相对风险因ULT药物和给药策略而异。关于ULT升级的数据有限。用秋水仙碱和利洛沙普预防耀斑可降低耀斑发生率。需要对预防的危害和最佳持续时间进行更多研究。
