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P454 Prediction of endoscopic activity in patients with Crohn’s disease: systematic review and external validation of published prediction models

E. C. Brand*1,2, S. G. Elias3, I. M. Minderhoud4, J. J. van der Veen1, F. Baert5, D. Laharie6, P. Bossuyt7, Y. Bouhnik8, A. Buisson9, G. Lambrecht10, E. Louis11, B. Pariente12, M. J. Pierik13, C. J. van der Woude14, G. R. D'Haens15, S. Vermeire16, B. Oldenburg1

1University Medical Centre Utrecht, Department of Gastroenterology and Hepatology, Utrecht, The Netherlands, 2University Medical Centre Utrecht, Laboratory for Translational Immunology, Utrecht, The Netherlands, 3University Medical Centre Utrecht, Julius Centre for Health Sciences and Primary Care, Utrecht, The Netherlands, 4Tergooi hospitals, Department of Gastroenterology and Hepatology, Blaricum/Hilversum, The Netherlands, 5AZ Delta, Department of Gastroenterology, Roeselare, Belgium, 6Hôpital Haut-Lévêque, Service d'Hépato-gastroentérologie et Oncologie Digestive, Bordeaux, France, 7Imelda General Hospital, IBD Clinic, Bonheiden, Belgium, 8Beaujon Hospital, APHP, Paris Diderot University, Department of Gastroenterology, Clichy, France, 9Estaing University Hospital, Department of Gastroenterology, Clermont-Ferrand, France, 10AZ Damiaan, Department of Gastroenterology, Oostende, Belgium, 11Liège University Hospital CHU, Department of Gastroenterology, Liège, Belgium, 12Huriez Hospital, Lille 2 University, Department of Gastroenterology, Lille, France, 13Maastricht University Medical Centre, Department of Gastroenterology and Hepatology, Maastricht, The Netherlands, 14Erasmus Medical Centre, Department of Gastroenterology and Hepatology, Rotterdam, The Netherlands, 15Amsterdam UMC, University of Amsterdam, Department of Gastroenterology, Amsterdam, The Netherlands, 16University Hospitals Leuven, Department of Gastroenterology and Hepathology, Leuven, Belgium

Background

Endoscopic healing (EH) is associated with an improved long-term prognosis and is therefore considered a key target in the treatment of Crohn’s disease (CD). Assessment of EH requires ileocolonoscopy, which is a costly and burdensome procedure. A non-invasive index, combining several predictors, to predict EH would simplify and improve management of CD in clinical practice. Published non-invasive models predicting EH often lack external validation. We reviewed the current literature for prediction models for ileocolonic endoscopic activity and subsequently compared their discriminatory abilities using two datasets.

Methods

We systematically searched PubMed, Embase, and the Cochrane libraries until 14 February 2018 for all published diagnostic models based on a combination of at least three predictors, for example, symptoms, serological, or faecal parameters, for ileocolonic endoscopic activity or EH in CD assessed by ileocolonoscopy. We subsequently evaluated the discriminatory value (area under the receiver-operating characteristic curve [AUC]) of the identified models in two separate cohorts, that is, the TAILORIX study1 (346 colonoscopies in 155 patients), and the development dataset of the Utrecht Activity Index (UAI)2 (93 colonoscopies in 82 patients). We corrected for clustering per patient employing the Obuchowski method.

Results

After screening 5303 titles, 21 studies reporting on 27 models with ≥3 predictors were identified. The most commonly used predictors, alongside other predictors in the models, were C-reactive protein (n = 18 [67%]) and faecal calprotectin (n = 13 [48%]). Twelve models were reported in sufficient detail for validation; of these, 8 models could be validated: 6/8 in the TAILORIX and 6/8 in the Utrecht Activity Index dataset. For a threshold of endoscopic activity measured by the CD Endoscopic Index of Severity (CDEIS) ≥3, the AUCs of the published models ranged from 0.55 to 0.85 in the TAILORIX dataset, and from 0.59 to 0.77 in the UAI development dataset (figure). When considering the discriminative ability of continuous values of faecal calprotectin the AUC was 0.82 and 0.79, in the TAILORIX and UAI dataset, respectively, and for CRP: 0.75 and 0.80, respectively.

Conclusion

Based on the discrimnatory ability published prediction models display limited benefit over faecal calprotectin or CRP in prediction of endoscopic activity in CD.

Figure. Discriminative ability of published prediction models, faecal calprotectin and CRP for CDEIS ≥3 as tested in the TAILORIX and UAI development dataset. If no AUC is indicated for a model, it was not validated in that particular dataset, because the predictors were not available. Beigel (2014) was only validated within the colonoscopies performed after the baseline colonoscopy in the TAILORIX dataset. Minderhoud (2015) was not validated in the UAI development dataset, because it was developed in that dataset. The model of Nakarai (2014) was only developed and thus validated for patients with a low CRP value. AUC, area under the receiver operating characteristic curve; CRP, C-reactive protein, UAI, Utrecht Activity Index development dataset.

Reference

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9. Nakarai A, Kato J, Hiraoka S, et al. Slight increases in the disease activity index and platelet count imply the presence of active intestinal lesions in C-reactive protein-negative Crohn’s disease patients. Intern Med 2014;53:1905–11.