Jairath Vipul, Rubin David T, Verstockt Bram, Çekin Ayhan H, Abreu Maria T, Lees Charlie W, Fellmann Marc, Woolcott John C, Crosby Catherine, Wu Joseph, Bhattacharjee Abhishek, Herman David, Gu Guibao, Siegmund Britta
Department of Medicine and Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada.
University of Chicago Medicine Inflammatory Bowel Disease Center, Chicago, IL, USA.
Inflamm Bowel Dis. 2025 Apr 10;31(4):923-934. doi: 10.1093/ibd/izae111.
Biomarkers offer potential alternatives to endoscopies in monitoring ulcerative colitis (UC) progression and therapeutic response. This post hoc analysis of the ELEVATE UC clinical program assessed potential predictive values of fecal calprotectin (fCAL) and high-sensitivity C-reactive protein (hsCRP) as biomarkers and associated responses to etrasimod, an oral, once-daily, selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active UC, in 2 phase 3 clinical trials.
In ELEVATE UC 52 and ELEVATE UC 12, patients were randomized 2:1 to 2 mg of etrasimod once daily or placebo for 52 or 12 weeks, respectively. Fecal calprotectin/hsCRP differences between responders and nonresponders for efficacy end points (clinical remission, clinical response, endoscopic improvement-histologic remission [EIHR]) were assessed by Wilcoxon P-values. Sensitivity and specificity were presented as receiver operating characteristics (ROC) curves with area under the curve (AUC).
In ELEVATE UC 52 and ELEVATE UC 12, 289 and 238 patients received etrasimod and 144 and 116 received placebo, respectively. Baseline fCAL/hsCRP concentrations were generally balanced. Both trials had lower week-12 median fCAL levels in week-12 responders vs nonresponders receiving etrasimod for clinical remission, clinical response, and EIHR (all P < .001), with similar trends for hsCRP levels (all P < .01). For etrasimod, AUCs for fCAL/hsCRP and EIHR were 0.85/0.74 (week 12; ELEVATE UC 52), 0.83/0.69 (week 52; ELEVATE UC 52), and 0.80/0.65 (week 12; ELEVATE UC 12).
Fecal calprotectin/hsCRP levels decreased with etrasimod treatment; ROC analyses indicated a prognostic correlation between fCAL changes during induction and short-/long-term treatment response.
生物标志物为监测溃疡性结肠炎（UC）的进展和治疗反应提供了内镜检查的潜在替代方法。这项对ELEVATE UC临床项目的事后分析评估了粪便钙卫蛋白（fCAL）和高敏C反应蛋白（hsCRP）作为生物标志物的潜在预测价值，以及在两项3期临床试验中对etrasimod（一种口服、每日一次的选择性1,4,5-鞘氨醇-1-磷酸[S1P]受体调节剂，用于治疗中度至重度活动性UC）的相关反应。
在ELEVATE UC 52和ELEVATE UC 12试验中，患者分别以2:1的比例随机分配，接受每日一次2mg的etrasimod或安慰剂治疗52周或12周。通过Wilcoxon P值评估疗效终点（临床缓解、临床反应、内镜改善-组织学缓解[EIHR]）的反应者和无反应者之间的粪便钙卫蛋白/hsCRP差异。敏感性和特异性以曲线下面积（AUC）的受试者工作特征（ROC）曲线表示。
在ELEVATE UC 52和ELEVATE UC 12试验中，分别有289例和238例患者接受了etrasimod治疗，144例和116例患者接受了安慰剂治疗。基线fCAL/hsCRP浓度总体平衡。在两项试验中，对于临床缓解、临床反应和EIHR，接受etrasimod治疗的第12周反应者的第12周fCAL中位数水平均低于无反应者（所有P < .001），hsCRP水平也有类似趋势（所有P < .01）。对于etrasimod，fCAL/hsCRP和EIHR的AUC分别为0.85/0.74（第12周；ELEVATE UC 52）、0.83/0.69（第52周；ELEVATE UC 52）和0.80/0.65（第12周；ELEVATE UC 12）。
etrasimod治疗后粪便钙卫蛋白/hsCRP水平降低；ROC分析表明诱导期fCAL变化与短期/长期治疗反应之间存在预后相关性。
