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一种经过验证的基于网络的工具,可根据临床、血清学和基因变量显示个性化的克罗恩病预测结果。

A validated web-based tool to display individualised Crohn's disease predicted outcomes based on clinical, serologic and genetic variables.

作者信息

Siegel C A, Horton H, Siegel L S, Thompson K D, Mackenzie T, Stewart S K, Rice P W, Stempak J M, Dezfoli S, Haritunians T, Levy A, Baek M, Milgrom R, Dulai P S, Targan S R, Silverberg M S, Dubinsky M C, McGovern D P

机构信息

Dartmouth-Hitchcock Inflammatory Bowel Disease Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA.

Department of Medicine, Geisel School of Medicine at Dartmouth, Hanover, NH, USA.

出版信息

Aliment Pharmacol Ther. 2016 Jan;43(2):262-71. doi: 10.1111/apt.13460. Epub 2015 Nov 15.

Abstract

BACKGROUND

Early treatment for Crohn's disease (CD) with immunomodulators and/or anti-TNF agents improves outcomes in comparison to a slower 'step up' algorithm. However, there remains a limited ability to identify those who would benefit most from early intensive therapy.

AIM

To develop a validated, individualised, web-based tool for patients and clinicians to visualise individualised risks for developing Crohn's disease complications.

METHODS

A well-characterised cohort of adult patients with CD was analysed. Available data included: demographics; clinical characteristics; serologic immune responses; NOD2 status; time from diagnosis to complication; and medication exposure. Cox proportional analyses were performed to model the probability of developing a CD complication over time. The Cox model was validated externally in two independent CD cohorts. Using system dynamics analysis (SDA), these results were transformed into a simple graphical web-based display to show patients their individualised probability of developing a complication over a 3-year period.

RESULTS

Two hundered and forty three CD patients were included in the final model of which 142 experienced a complication. Significant variables in the multivariate Cox model included small bowel disease (HR 2.12, CI 1.05-4.29), left colonic disease (HR 0.73, CI 0.49-1.09), perianal disease (HR 4.12, CI 1.01-16.88), ASCA (HR 1.35, CI 1.16-1.58), Cbir (HR 1.29, CI 1.07-1.55), ANCA (HR 0.77, CI 0.62-0.95), and the NOD2 frameshift mutation/SNP13 (HR 2.13, CI 1.33-3.40). The Harrell's C (concordance index for predictive accuracy of the model) = 0.73. When applied to the two external validation cohorts (adult n = 109, pediatric n = 392), the concordance index was 0.73 and 0.75, respectively, for adult and pediatric patients.

CONCLUSIONS

A validated, web-based tool has been developed to display an individualised predicted outcome for adult patients with Crohn's disease based on clinical, serologic and genetic variables. This tool can be used to help providers and patients make personalised decisions about treatment options.

摘要

背景

与采用较慢的“逐步升级”方案相比,使用免疫调节剂和/或抗TNF药物对克罗恩病(CD)进行早期治疗可改善治疗效果。然而,识别那些能从早期强化治疗中获益最大的患者的能力仍然有限。

目的

开发一种经过验证的、个性化的基于网络的工具,供患者和临床医生查看患克罗恩病并发症的个性化风险。

方法

对一组特征明确的成年CD患者进行分析。可用数据包括:人口统计学资料;临床特征;血清学免疫反应;NOD2状态;从诊断到出现并发症的时间;以及用药情况。进行Cox比例分析以模拟随时间发生CD并发症的概率。该Cox模型在两个独立的CD队列中进行了外部验证。使用系统动力学分析(SDA),将这些结果转化为一个简单的基于网络的图形显示,向患者展示他们在3年内发生并发症的个性化概率。

结果

最终模型纳入了243例CD患者,其中142例出现了并发症。多变量Cox模型中的显著变量包括小肠疾病(风险比[HR]2.12,置信区间[CI]1.05 - 4.29)、左半结肠疾病(HR 0.73,CI 0.49 - 1.09)、肛周疾病(HR 4.12,CI 1.01 - 16.88)、抗酿酒酵母抗体(ASCA)(HR 1.35,CI 1.16 - 1.58)、抗嗜中性粒细胞胞浆抗体(Cbir)(HR 1.29,CI 1.07 - 1.55)、抗中性粒细胞胞浆抗体(ANCA)(HR 0.77,CI 0.62 - 0.95)以及NOD2移码突变/SNP13(HR 2.13,CI 1.33 - 3.40)。Harrell's C(模型预测准确性的一致性指数)= 0.73。当应用于两个外部验证队列(成年患者n = 109,儿科患者n = 392)时,成年患者和儿科患者的一致性指数分别为0.73和0.75。

结论

已开发出一种经过验证的基于网络的工具,可根据临床、血清学和基因变量显示成年克罗恩病患者的个性化预测结果。该工具可用于帮助医疗服务提供者和患者就治疗方案做出个性化决策。

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