背景:生物标志物在监测溃疡性结肠炎(UC)进展和治疗反应方面为内窥镜检查提供了潜在的替代方案。对ELEVATEUC临床计划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值以及对etrasimod的相关反应,一个口头,每天一次,选择性鞘氨醇1-磷酸(S1P)1,4,5受体调节剂用于治疗中度至重度活动性UC,在2个3期临床试验中。
方法:在ELEVATEUC52和ELEVATEUC12中,患者随机分为2:1至2mg依曲莫德每天一次或安慰剂52或12周,分别。疗效终点反应者和无反应者之间的粪便钙卫蛋白/hsCRP差异(临床缓解,临床反应,内镜改善-组织学缓解[EIHR])通过WilcoxonP值进行评估。敏感性和特异性表示为受试者操作特征(ROC)曲线以及曲线下面积(AUC)。
结果:在ELEVATEUC52和ELEVATEUC中,12、289和238名患者接受了etrasimod,144和116名患者接受了安慰剂,分别。基线fCAL/hsCRP浓度通常是平衡的。两项试验在第12周应答者中的第12周中位数fCAL水平较低,而在接受etrasimod进行临床缓解的非应答者中,临床反应,和EIHR(所有P<.001),hsCRP水平趋势相似(均P<0.01)。对于Etrasimod来说,fCAL/hsCRP和EIHR的AUC为0.85/0.74(第12周;ELEVATEUC52),0.83/0.69(第52周;ELEVATEUC52),和0.80/0.65(第12周;升高UC12)。
结论:粪便钙卫蛋白/hsCRP水平随着etrasimod治疗而降低;ROC分析表明诱导期间fCAL变化与短期/长期治疗反应之间存在预后相关性。
我们显示了每天一次服用2mg依曲莫德的患者的粪便钙卫蛋白(fCAL)和高敏C反应蛋白(hsCRP)水平与疗效结果之间的关系。fCAL水平可能是长期疗效终点成就的早期指标。
BACKGROUND: 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.
METHODS: 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).
RESULTS: 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).
CONCLUSIONS: 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.
We show associations between fecal calprotectin (fCAL) and high-sensitivity C-reactive protein (hsCRP) levels with efficacy outcomes among patients receiving 2 mg of etrasimod once daily, and that fCAL levels may be an early indicator of the achievement of long-term efficacy end point achievement.