Background & Aims

Endoscopic healing, an important target of treatment for Crohn’s disease (CD), requires ileocolonoscopy, which is costly and burdensome. We investigated whether published noninvasive models (based on symptoms and biomarkers) to evaluate CD activity have sufficient accuracy to replace ileocolonoscopy.

Methods

We performed a systematic review of published noninvasive diagnostic models to evaluate CD activity that used endoscopic features of activity (endoscopic activity) or healing as the reference standard. We externally validated these models for the outcome endoscopic activity (CD endoscopic index of severity scores, ≥3) using data from the a randomized controlled trial investigating tailored treatment with infliximab for active luminal Crohn's disease (TAILORIX) study (346 ileocolonoscopies in 155 patients) and the Utrecht Activity Index (UAI) study (93 ileocolonoscopies in 82 patients). We calculated the area under the receiver operating characteristic curves (AUROCs) for the models using data from these studies, and compared the performance of these models against measurements of fecal calprotectin (FC) and C-reactive protein (CRP).

Results

We screened 5303 articles and identified 27 models (from 21 studies) for our analysis. Seven models could be validated externally; in the TAILORIX data set, these models identified patients with endoscopic activity with AUROC values ranging from 0.61 (95% CI, 0.51–0.70) to 0.81 (95% CI, 0.76–0.86). In this data set, the AUROC value for FC concentration was 0.79 (95% CI, 0.74–0.85) and the AUROC value for CRP level was 0.72 (95% CI, 0.66–0.77). The AUROC values for the validation in the UAI data set were similar. In the TAILORIX and/or UAI data set, 4 of the 7 models, as well as the FC and CRP assays, were able to identify patients with endoscopic activity with positive predictive values of 90% or more. Two of the 7 models (but not the FC or CRP values) identified patients without endoscopic activity with a negative predictive value (NPV) of 90% or more, leading to correct prediction of endoscopic healing in 3.2% to 11.3% of all patients. For example, applying the Herranz–Bachiller model (1 of 7 models) at a NPV of 92.1% and a positive predictive value of 91.9% correctly identified 35.7% of all patients in whom ileocolonoscopy could be avoided for expected endoscopic activity or healing but incorrectly identified 3.2% of all patients. Most ileocolonoscopies (66.5% in TAILORIX and 72.6% in the UAI of all ileocolonoscopies) could be avoided correctly based on concentrations of FC of 100 μg/g or less and 250 μg/g or higher. However, using this range of FC concentrations to identify patients who do not require ileocolonoscopy caused 18.7% of all patients in the TAILORIX cohort and 19.8% of all patients in the UAI cohort to be predicted incorrectly to have endoscopic activity or healing.

Conclusions

In a systematic review and external validation of noninvasive models to identify patients with endoscopic activity of CD, we found only 2 of 7 models evaluated to have NPVs of 90% or more, however, leading to correctly predicted EH in only a small proportion of patients. Ileocolonoscopy therefore remains the mainstay to evaluate CD mucosal disease activity and healing.

中文翻译：

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基于症状和生物标志物的预测模型的系统评价和外部验证，用于识别克罗恩病的内窥镜活动。

背景与目标

内窥镜愈合是克罗恩病 (CD) 治疗的重要目标，需要回肠结肠镜检查，成本高且负担重。我们调查了已发表的评估 CD 活动的无创模型（基于症状和生物标志物）是否具有足够的准确性来取代回肠镜检查。

方法

我们对已发表的无创诊断模型进行了系统审查，以评估 CD 活动，这些模型使用活动（内窥镜活动）或愈合的内窥镜特征作为参考标准。我们使用来自一项随机对照试验的数据对这些模型的内窥镜活动结果（CD 内窥镜严重程度评分指数，≥3）进行了外部验证，该试验调查了英夫利昔单抗针对活动性克罗恩病的定制治疗（TAILORIX）研究（155 名患者进行了 346 次回肠结肠镜检查）和乌得勒支活动指数 (UAI) 研究（82 名患者进行了 93 次回肠结肠镜检查）。我们使用这些研究的数据计算了模型的受试者工作特征曲线 (AUROC) 下面积，并将这些模型的性能与粪便钙卫蛋白 (FC) 和 C 反应蛋白 (CRP) 的测量值进行了比较。

结果

我们筛选了 5303 篇文章并确定了 27 个模型（来自 21 项研究）用于我们的分析。可以从外部验证七个模型；在 TAILORIX 数据集中，这些模型通过 AUROC 值范围从 0.61（95% CI，0.51-0.70）到 0.81（95% CI，0.76-0.86）来识别具有内窥镜活动的患者。在该数据集中，FC 浓度的 AUROC 值为 0.79（95% CI，0.74-0.85），CRP 水平的 AUROC 值为 0.72（95% CI，0.66-0.77）。UAI 数据集中验证的 AUROC 值相似。在 TAILORIX 和/或 UAI 数据集中，7 个模型中的 4 个以及 FC 和 CRP 检测能够识别具有 90% 或更高阳性预测值的内窥镜活动患者。7 个模型中的两个（但不是 FC 或 CRP 值）识别出没有内窥镜活动的患者，其阴性预测值 (NPV) 为 90% 或更高，导致所有患者中 3.2% 至 11.3% 的内窥镜愈合预测正确。例如，以 92.1% 的 NPV 和 91.9% 的阳性预测值应用 Herranz-Bachiller 模型（7 个模型中的 1 个）正确识别了 35.7% 可以避免回肠结肠镜检查以进行预期内窥镜活动或愈合但不正确的患者确定了所有患者的 3.2%。大多数回肠结肠镜检查（TAILORIX 为 66.5%，所有回肠结肠镜检查的 UAI 为 72.6%）基于 100 μg/g 或更低和 250 μg/g 或更高的 FC 浓度可以正确避免。然而，使用这个范围的 FC 浓度来识别不需要回肠镜检查的患者会导致 18。

结论

在用于识别内窥镜活动性 CD 患者的无创模型的系统评价和外部验证中，我们发现 7 个模型中只有 2 个被评估为具有 90% 或更高的 NPV，然而，仅在一小部分患者中导致正确预测 EH . 因此，回肠结肠镜检查仍然是评估 CD 黏膜疾病活动和愈合的主要手段。