University of South Australia and Southern Adelaide Local Health Network, Adelaide, South Australia, Australia.
University of South Australia, Adelaide, South Australia, and Monash University, Melbourne, Victoria, Australia.
Arthritis Care Res (Hoboken). 2024 Jun;76(6):871-881. doi: 10.1002/acr.25309. Epub 2024 Mar 14.
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.
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.
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.
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.
我们系统地检查了起始或升级不同尿酸降低疗法（ULT）后的比较痛风发作风险、有和没有伴随的预防发作治疗的比较发作风险、与预防发作治疗相关的不良事件发生率以及预防发作治疗的最佳持续时间。
我们从建立到 2021 年 11 月在 Medline、Embase、Web of Science 和 Cochrane 数据库以及临床试验登记处搜索了调查起始或升级 ULT 的成年痛风患者的试验。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）。使用修订后的 Cochrane 偏倚风险工具评估了偏差。
我们确定了 3775 条记录，其中 29 篇出版物（27 项试验）被纳入。与安慰剂加预防治疗相比，发作的 RR 范围从非布司他 40mg 加预防治疗的 1.08（95%置信区间 [CI] 0.87-1.33）到非布司他 80mg 加 lesinurad 400mg 加预防治疗的 2.65（95% CI 1.58-4.45）。与 ULT 单独治疗相比，ULT 加 rilonacept 160mg（RR 0.35 [95% CI 0.25-0.50]）、ULT 加 rilonacept 80mg（RR 0.43 [95% CI 0.31-0.60]）和 ULT 加秋水仙碱（RR 0.50 [95% CI 0.35-0.72]）的发作 RR 较低。对于其他预防发作治疗和预防发作危害以及最佳持续时间，证据有限。主要由于缺失结局数据和报告结果选择的偏倚，71.4%和 63.4%的研究在发作和不良事件方面被评估为高偏倚风险。
引入 ULT 时的发作 RR 因 ULT 药物和剂量策略而异。ULT 升级的数据有限。秋水仙碱和 rilonacept 的预防发作治疗可降低发作发生率。需要更多关于预防发作治疗的危害和最佳持续时间的研究。
