Development and validation of a novel Endoscopic ulcer Activity Score for Evaluation of Crohn's Disease (EASE-CD) using data from two randomised controlled trials.

Existing indices for evaluating endoscopic Crohn's disease activity are only modestly correlated with clinical disease activity, contain items with ambiguous definitions and poor interobserver reliability, and do not have validated thresholds for defining clinically relevant changes.

现有的评估内窥镜下克罗恩病活动的指数与临床病变活动的相关性仅属中等，包含定义模糊、观察者间可靠性差的项目，并且没有经过验证的阈值来定义临床上相关的变化。

To address these issues, we conducted a multiphase study to develop and validate a novel endoscopic index for Crohn's disease.

为了解决这些问题，我们进行了一项多阶段研究，以开发和验证一种新的克罗恩病内镜指数。

Methods

Paired baseline and post-induction ileocolonoscopy videos from a phase 3b adalimumab trial (NCT00348283) and phase 2 risankizumab trial (NCT02031276) were assessed by multiple central readers using candidate endoscopic items with face validity derived using modified RAND/UCLA appropriateness methods.

通过使用修改的RAND/UCLA适宜性方法得出的具有表面有效性的候选内镜项目，由多个中心读者评估了3b期阿达木单抗试验（NCT00348283）和2期risankizumab试验（NCT02031276）的基线和诱导后回结肠镜视频对。

The four readers were masked to all clinical information, including treatment assignment and patient symptom scores.

四位读者对所有临床信息（包括治疗分配和患者症状评分）均不知情。

A total of 112 and 99 paired ileocolonoscopy videos with treatment assignment were available from the adalimumab trial and risankizumab trial, respectively; after the four readers assessed the 112 videos, two readers then reassessed 44 post-treatment videos to assess inter-rater reliability in index development.

在阿达木单抗试验和瑞舒伐单抗试验中，分别有112对和99对回盲肠镜检查视频可用于治疗分配；在四位读者评估了112个视频后，又有两位读者重新评估了44个治疗后的视频，以评估指标开发中的评分者间信度。

Items with acceptable inter-rater reliability (with an intraclass correlation coefficient [ICC] of ≥0·41) and responsiveness (win probability [WinP], the probability that a patient receiving active treatment has a better endoscopy score than a patient receiving placebo, of ≥0·56) were included as covariables in regression for model building with internal validation with bootstrapping.

具有可接受的评价者间信度（组内相关系数[ICC]≥0·41）和反应性（胜率[WinP]，即接受活性治疗的患者比接受安慰剂的患者有更好的内镜评分的概率，≥0·56）的项目被包括在回归模型构建中，该模型通过自助法进行了内部验证。

External validation was conducted using the paired videos from the risankizumab trial.

使用risankizumab试验中的配对视频进行了外部验证。

Results

Ten endoscopic items met ICC and WinP thresholds and were considered for novel index development.

十个内镜项目满足ICC和WinP阈值，被考虑用于新指数的开发。

They included items from the SES-CD (presence and size of ulcers, extent of ulcerated surface, and extent of affected surface) and CDEIS (percentage of surface involved by Crohn's disease, percentage of ulcerated surface, deep ulceration, and superficial ulceration) and exploratory items (presence of Crohn's disease-related lesions, Crohn's disease-related lesion severity, and Crohn's disease-related lesion involvement).

它们包括来自SES-CD（溃疡的存在和大小、溃疡表面的范围以及受影响表面的范围）和CDEIS（克罗恩病影响的表面百分比、溃疡表面的百分比、深溃疡和浅溃疡）以及探索性项目（克罗恩病相关病变的存在、克罗恩病相关病变的严重程度和克罗恩病相关病变的涉及范围）。

The final model, Endoscopic ulcer Activity Score for Evaluating CD (EASE-CD), included the presence and size of ulcerations measured on an ordinal scale of 0 (none), 1 (ulcers <5 mm), 2 (ulcers between 5 mm and 20 mm), and 3 (ulcers >20 mm); the presence or absence of deep ulcerations measured dichotomously, with 0 for absent and 1 for present; and the proportion of ulcerated surface area, expressed as a continuous proportion from 0-1, with each item evaluated and averaged across visualised bowel segments.

最终模型，即用于评估克罗恩病（CD）的内镜溃疡活动评分（EASE-CD），包括按等级量表评估的溃疡存在及其大小，等级为0（无溃疡）、1（溃疡<5毫米）、2（溃疡介于5毫米和20毫米之间）以及3（溃疡>20毫米）；深度溃疡的存在与否以二分法测量，0表示不存在，1表示存在；以及溃疡表面积比例，以0-1的连续比例表示，每个项目在可视肠段中进行评估并取平均值。

The total score ranges from 0-100 with higher scores indicating greater endoscopic activity.

总分范围为0-100，分数越高表示内镜活动性越大。

The r2 and optimism adjusted r2 of EASE-CD in internal validation were 0·608 and 0·554, and the index was well calibrated with a slope of 0·983.

在内部验证中，EASE-CD的r2和调整后的r2分别为0.608和0.554，且该指数校准良好，斜率为0.983。

In external validation, the adjusted r2 was 0·565 and the calibration slope was 0·997.

在外部验证中，调整后的r2为0.565，校准斜率为0.997。

EASE-CD also demonstrated substantial inter-rater reliability (ICC 0·798 [95% CI 0·711-0·836]) and a large degree of responsiveness (WinP 0·769 [95% CI 0·658-0·851], p<0·001) in external validation.

EASE-CD还展示了显著的评分者间信度（ICC 0·798 [95% 置信区间 0·711-0·836]）和在外部验证中具有很大的反应性（WinP 0·769 [95% 置信区间 0·658-0·851], p<0·001）。

A 10-point reduction in EASE-CD had 82·4% specificity (95% CI 78·6-86·0) and 69·9% sensitivity (63·3-76·4) for endoscopic response, defined by at least 50% reduction in SES-CD or CDEIS.

EASE-CD评分降低10分对于内镜反应的特异性为82·4%（95% 置信区间 78·6-86·0），敏感性为69·9%（63·3-76·4），内镜反应定义为SES-CD或CDEIS至少减少50%。

Ulcer-free endoscopic remission results in EASE-CD score of 0.

内镜下无溃疡的缓解结果导致EASE-CD评分为0。

interpretation

EASE-CD is a novel, internally and externally validated continuous measure of endoscopic ulcer activity in Crohn's disease that is reliable and responsive to treatment.

EASE-CD是一种新颖的、经过内部和外部验证的克罗恩病内镜溃疡活动的连续测量方法，它对治疗反应可靠。

funding

None.

无。