265 Predicting endoscopic disease activity in IBD Introduction Crohn’s disease (CD) and ulcerative colitis (UC) are chronic idiopathic inflammatory bowel diseases (IBD), characterized by an inappropriate and uncontrolled immune response, stimulated by the gut microbiome in a genetically susceptible host.1 Typically, patients with IBD follow a disease course consisting of alternating exacerbations and periods of remission.2 In IBD, the extent of inflammatory disease activity is preferably established by endoscopy, that is translated to validated scoring systems, such as the Mayo endoscopic subscore for UC and the Simple Endoscopic Score for CD (SES-CD).3,4 Frequent monitoring of IBD disease activity is crucially important, since longlasting subclinical disease activity is known to increase the risk of future surgical interventions and hospitalization and to decrease patients’ quality of life and economic participation.5-8 Endoscopic examination is still the most reliable approach for diagnosing the presence and extent of IBD disease activity.9 This procedure, however, has several disadvantages, such as a high patient burden, but also risks of serious complications, like bowel perforation or bleeding. In addition, it is costly and time-consuming. Alternatives for endoscopy are therefore urgently needed. Non-endoscopic disease indices, such as the Crohn’s Disease Activity Index (CDAI) or Harvey Bradshaw Index (HBI) for CD and the Simple Clinical Colitis Activity Index (SCCAI) for UC, fail to correlate well with endoscopically-proven intestinal inflammation.10-13 Biomarkers for endoscopic disease activity have also been explored and are becoming increasingly important to predict the level of mucosal inflammation in IBD. Fecal calprotectin (FC) and serum C-reactive protein (CRP) levels are now widely used and considered predictive markers for the degree of inflammation, but also show inconsistent correlationwithmucosal inflammationwhen compared to endoscopy.14-16 This illustrates the need for better diagnostic measures for IBD exacerbations that preferably can also be applied to patients with subclinical disease activity.17 Cytokines play a pivotal role in the pathogenesis of IBD, controlling intestinal inflammation and disease activity and might be better predictive markers for disease activity than FC and CRP.1820 In many diseases, combinations of inflammatory cytokines have been shown to be predictive for inflammatory state and are therewith adequate biomarkers for non-invasive disease activity monitoring.21 Recently, we showed that for CD a positive correlation exists between multiple Th1- and Th17- associated serum cytokines and fecal calprotectin levels.22 Although no endoscopic results were available for that patient cohort, it demonstrated the proof of principle and value of selected Th1- and Th17-associated serum cytokines for measuring inflammation in IBD. As a next step, we aimed to evaluate the potential of a combined set of such cytokines to predict endoscopic disease activity, as one single biomarker will be unlikely to accurately predict the mucosal status in IBD. Therefore, a limited set of 10 candidate inflammatory biomarkers (C-reactive protein (CRP), serum amyloid A (SAA), IFN-γ, TNF-α, IL-6, IL-8, IL-10, IL-17A, Eotaxin-1 and Eotaxin-3) was selected based on results from the aforementioned pilot-study and available literature.18, 20-22 In the present study, we investigated a selection of 10 inflammatory biomarkers involved in IBD and their association to inflammatory disease activity as evaluated by endoscopic examination. Correlations between individual biomarkers and endoscopic disease activity were analyzed and used to compose an accurate prediction tool for the level of endoscopic disease activity, based on a subset of these biomarkers. Finally, we compared the predictive accuracy of this panel of biomarkers with commonly applied measures of disease activity, such as clinical indices (HBI/SCCAI), serum CRP and FC levels.
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