BACKGROUND & AIMS Noninvasive tests to measure endoscopic activity in patients with Crohn's disease (CD) have limitations. We aimed to develop a test to identify patients in remission, based on endoscopic analysis, and monitor CD activity based on serum levels of proteins. METHODS We developed a test to measure 13 proteins in blood (ANG1, ANG2, CRP, SAA1, IL7, EMMPRIN, MMP1, MMP2, MMP3, MMP9, TGFA, CEACAM1, and VCAM1), called the endoscopic healing index [EHI], using samples from 278 patients with CD from a multinational training cohort. We validated the test using 2 independent cohorts of patients with CD: 116 biologic-naive patients with early-stage CD (validation cohort 1) and 195 biologic-exposed patients with chronic CD (validation cohort 2). The ability of the test to identify patients with active disease vs patients in remission (defined as a simple endoscopic score for CD of ≤2 and ≤1 in each segment, or a total CD endoscopic index of severity score <3) was assessed by using area under receiver operating characteristic curve (AUROC) analysis. The diagnostic accuracy of the test was compared with that of measurement of serum C-reactive protein (CRP) and fecal calprotectin. RESULTS The EHI scores range from 0 to 100 units; higher scores indicate more severe CD activity, based on endoscopy findings. The EHI identified patients in remission with an AUROC of 0.962 in validation cohort 1 (95% confidence interval, 0.942-0.982) and an AUROC of 0.693 in validation cohort 2 (95% confidence interval, 0.619-0.767), regardless of CD location or phenotype. A cutoff value of 20 points identified patients in remission with the highest level of sensitivity (97.1% in validation cohort 1 and 83.2% in validation cohort 2), with specificity values of 69.0% and 36.6%, respectively. A cutoff value of 50 points identified patients in remission with the highest level of specificity (100% in validation cohort 1 and 87.8% in validation cohort 2), with sensitivity values of 37.3% and 30.0%, respectively. The EHI identified patients in remission with a significantly higher AUROC value than the test for CRP (0.876, P < .001 in validation cohort 1 and 0.624, P = .109 in validation cohort 2). In analysis of patients with available FC measurements, the AUROC value for the EHI did not differ significantly from that of measurement of FC (AUROC, 0.950 for EHI vs AUROC, 0.923 for FC; P = .147 in validation cohort 1 and AUROC, 0.803 for EHI vs AUROC, 0.854 for FC; P = .298 in validation cohort 2). CONCLUSIONS We developed an index called the EHI to identify patients with CD in endoscopic remission based on blood levels of 13 proteins. The EHI identified patients with resolution of endoscopic disease activity, with good overall accuracy, although with variation between the 2 cohorts assessed. The EHI AUROC values were comparable to measurement of FC and higher than measurement of serum CRP. The test might be used in practice to assess endoscopic activity in patients with CD.

中文翻译：

---

基于血清蛋白质水平监测克罗恩病患者内窥镜活动的测试的开发和验证。


背景和目的 测量克罗恩病 (CD) 患者内窥镜活动的无创测试有其局限性。我们的目标是开发一种测试，基于内窥镜分析来识别缓解患者，并根据血清蛋白质水平监测 CD 活性。方法 我们开发了一种测试来测量血液中的 13 种蛋白质（ANG1、ANG2、CRP、SAA1、IL7、EMMPRIN、MMP1、MMP2、MMP3、MMP9、TGFA、CEACAM1 和 VCAM1），称为内镜愈合指数 [EHI]，使用来自跨国培训队列的 278 名 CD 患者的样本。我们使用 2 个独立的 CD 患者队列验证了该测试：116 名未接受过生物制剂的早期 CD 患者（验证队列 1）和 195 名接受过生物制剂的慢性 CD 患者（验证队列 2）。该测试识别活动性疾病患者与缓解患者的能力（定义为每个节段的 CD 简单内镜评分≤2 和 ≤1，或严重评分 <3 的总 CD 内镜指数）通过以下方法进行评估：接受者操作特征曲线（AUROC）分析下的面积。该测试的诊断准确性与血清C反应蛋白（CRP）和粪便钙卫蛋白的测量结果进行了比较。结果 EHI 分数范围从 0 到 100 个单位；根据内窥镜检查结果，分数越高表明 CD 活动越严重。 EHI 确定缓解患者在验证队列 1 中的 AUROC 为 0.962（95% 置信区间，0.942-0.982），在验证队列 2 中 AUROC 为 0.693（95% 置信区间，0.619-0.767），无论 CD 位置或表型。 20 分的临界值确定了缓解患者的敏感性最高（验证队列 1 中为 97.1%，验证队列 2 中为 83.2%），特异性值分别为 69.0% 和 36.6%。 50 分的临界值确定了具有最高特异性的缓解患者（验证队列 1 中为 100%，验证队列 2 中为 87.8%），敏感性值分别为 37.3% 和 30.0%。 EHI 识别出缓解期患者的 AUROC 值显着高于 CRP 测试（验证队列 1 中为 0.876，P < .001，验证队列 2 中为 0.624，P = .109）。在对具有可用 FC 测量值的患者进行分析时，EHI 的 AUROC 值与 FC 的测量值没有显着差异（EHI 的 AUROC 为 0.950，FC 的 AUROC 为 0.923；验证队列 1 中 P = 0.147，AUROC 为 0.803对于 EHI 与 AUROC，FC 为 0.854；验证队列 2 中 P = 0.298）。结论 我们开发了一个名为 EHI 的指数，根据 13 种蛋白质的血液水平来识别内镜缓解的 CD 患者。 EHI 识别出内窥镜疾病活动已得到缓解的患者，总体准确性良好，尽管所评估的 2 个队列之间存在差异。 EHI AUROC 值与 FC 测量值相当，并且高于血清 CRP 测量值。该测试可在实践中用于评估 CD 患者的内窥镜活动。