Department of Medicine, University of Otago, Christchurch, P.O. Box 4345, Christchurch, New Zealand.
Musculoskeletal Statistics Unit, The Parker Institute, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark; Department of Rheumatology, Odense University Hospital, Denmark; Department of Medicine, Vejle Hospital, Denmark.
Semin Arthritis Rheum. 2018 Oct;48(2):293-301. doi: 10.1016/j.semarthrit.2018.02.009. Epub 2018 Feb 21.
The primary efficacy outcome in trials of urate lowering therapy (ULT) for gout is serum urate (SU). The aim of this study was to examine the strength of the relationship between SU and patient-important outcomes to determine whether SU is an adequate surrogate endpoint for clinical trials.
Multiple databases through October 2017 were searched. Randomized controlled trials comparing any ULT in people with gout with any control or placebo, ≥three months duration were included. Open label extension (OLE) trial data were included in secondary analyses. Standardized data elements were extracted independently by two reviewers.
Ten RCTs and 3 OLE studies were identified. From the RCTs (maximum duration 24 months) meta-regression did not reveal an association between the relative risk of a gout flare and the difference in proportions of individuals with SU < 6mg/dL (P = 0.47; R = 8%). In a post hoc analysis, the ratio of the time in months at which the proportion of individuals having a flare was reported/time in months at which the proportion of individuals with SU < 6mg/dL was reported was calculated and studies where the ratio was <2 were excluded. Using the remaining 6 studies there was an association between proportion of individuals achieving SU < 6mg/dL and gout flares (over patient years). Duration of ULT was inversely associated with the proportion of patients experiencing a flare. Study duration and variability in reporting of outcomes limited the analysis. Observational studies supported the trend of fewer flares in those with lower SU.
Based on aggregate clinical trial-level data an association between SU and gout flare could not be confirmed. However, based on observational ecological study design data-including longer duration extension studies-SU < 6mg/dL was associated with reduced gout flares.
降尿酸治疗（ULT）治疗痛风的主要疗效终点是血清尿酸（SU）。本研究旨在探讨 SU 与患者重要结局的关系强度，以确定 SU 是否为临床试验的合适替代终点。
通过 2017 年 10 月前的多个数据库进行搜索。纳入比较任何 ULT 与任何对照或安慰剂治疗痛风患者、持续时间≥3 个月的随机对照试验。将开放标签扩展（OLE）试验数据纳入次要分析。两名评审员独立提取标准化数据元素。
确定了 10 项 RCT 和 3 项 OLE 研究。从 RCT （最长 24 个月）的荟萃回归分析中，没有发现痛风发作的相对风险与 SU<6mg/dL 的个体比例差异之间存在关联（P=0.47；R=8%）。在事后分析中，计算了报告痛风发作个体比例的月份数与报告 SU<6mg/dL 的个体比例的月份数之比，并排除比值<2 的研究。使用其余 6 项研究，SU<6mg/dL 的个体比例与痛风发作之间存在关联（超过患者年）。ULT 的持续时间与患者出现发作的比例呈反比。研究持续时间和结局报告的变异性限制了分析。观察性研究支持 SU 越低痛风发作越少的趋势。
基于汇总临床试验水平的数据，不能确认 SU 与痛风发作之间的关联。然而，基于观察性生态研究设计的数据，包括更长时间的延伸研究，SU<6mg/dL 与减少痛风发作有关。
