Canakinumab's Effect Against Subsequent Gout Flares and High-Sensitivity C-Reactive Protein Levels: A Causal Mediation Analysis.
Canakinumab's Effect Against Subsequent Gout Flares and High-Sensitivity C-Reactive Protein Levels: A Causal Mediation Analysis.
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卡那奴单抗对随后的痛风发作和高敏 C 反应蛋白水平的影响：因果中介分析。
DOI：
10.1002/acr.24832
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发表时间：
2023
影响因子：
4.7
通讯作者：
Solomon,DanielH
中科院分区：
文献类型：
--
作者：
Yoshida,Kazuki;Glynn,RobertJ;Choi,HyonK;Everett,BrendanM;Li,Yi;MacFadyen,JeanG;Ridker,PaulM;Solomon,DanielH
本研究的目的是量化早期抑制高敏C反应蛋白(HsCRP)水平作为Canakinumab对未来痛风发作的保护作用的生物标志物的价值。方法我们对Canakinumab抗炎血栓形成结果研究的痛风发作进行了一项特殊的因果中介分析。记录hsCRP水平的3个月变化是感兴趣的中介因素。在因果中介分析中，我们对hsCRP水平进行线性回归，对痛风发作结果进行COX或WEIBUR回归。结果我们分析了9221例非痛风患者和747例痛风患者。与安慰剂相比，痛风发作的Cox回归风险比(HR)为0.50(95%可信区间[95%CI]0.37-0.68)，其中6%是通过前3个月hsCRP水平降低的中介效应解释的。在痛风流行亚组中，HR为0.58(95%CI为0.36~0.95)，其中31%可用hsCRP水平降低的中介效应来解释。威布尔分析给出的比例中介估计为47%。在无痛风流行的亚组中，hsCRP水平下降的间接影响尚不清楚。结论在整个队列中，hsCRP水平前3个月的下降不是Canakinumab对未来痛风发作的保护作用的良好生物标志物。在痛风流行的患者中，早期hsCRP水平降低作为白细胞介素1β抑制剂未来痛风发作益处的生物标志物可能具有潜在作用。
ObjectiveThe objective of this study was to quantify the value of early suppression of high‐sensitivity C‐reactive protein (hsCRP) levels as a biomarker of the protective role of canakinumab against future gout flares.MethodsWe conducted a post hoc causal mediation analysis of the Canakinumab Anti‐Inflammatory Thrombosis Outcome Study for gout flares. The 3‐month change in the log hsCRP level was the mediator of interest. We used linear regression for the hsCRP level mediator and Cox or Weibull regression for gout‐flare outcomes, combining them in causal mediation analysis. We examined the cohort overall, as well as stratified by prevalent gout at baseline.ResultsWe analyzed 9,221 patients without prevalent gout and 747 with prevalent gout. The Cox regression hazard ratio (HR) for a gout flare was 0.50 (95% confidence interval [95% CI] 0.37–0.68) comparing canakinumab with placebo, of which 6% was explained by the mediated effect through hsCRP level reduction in the first 3 months. In the prevalent‐gout subgroup, the HR was 0.58 (95% CI 0.36–0.95), of which 31% was explained by the mediated effect through hsCRP level reduction. The Weibull analysis gave a proportion‐mediated estimate of 47%. The indirect effect via hsCRP level reductions was unclear in the subgroup without prevalent gout.ConclusionThe first 3‐month reduction in hsCRP level was not a good biomarker for canakinumab's protective effect on future gout flares in the overall cohort. Among patients with prevalent gout, there may be a potential role for early hsCRP level reduction as a biomarker for interleukin‐1β inhibitors' future gout‐flare benefit.