Endoscopic Disease Activity In Patients Research Articles

P454 Systemic free thiols associate with clinical and biochemical disease activity in Inflammatory Bowel Disease: a prospective diagnostic validation study

Abstract Background In the pathophysiology of inflammatory bowel diseases (IBD), oxidative stress plays an important role. Lower levels of plasma free thiols (FT) reflect a higher oxidative stress burden and correlate with IBD disease activity. However, their clinical significance as biomarker for disease activity remains unclear. This study aimed to prospectively validate the utility of plasma FT levels as biomarker for clinical, biochemical, and endoscopic disease activity in patients with IBD. Methods In an ongoing prospective diagnostic trial aiming to include 100 IBD patients, we conducted an interim analysis of plasma FT levels in 52 patients with IBD (24 Crohn's disease [CD], 21 ulcerative colitis [UC], and 7 patients with undetermined IBD). Clinical disease activity was quantified by the Harvey-Bradshaw Index (HBI) for CD and Simple Clinical Colitis Activity Index (SCCAI) for UC. Biochemical disease activity was determined by measuring blood C-reactive protein [CRP] and faecal calprotectin [fCal]). Endoscopic disease activity was quantified with the Mayo endoscopic subscore for UC and the Simple Endoscopic Score (SES-CD) for CD. Plasma FT levels were assessed for correlations with disease activity parameters using linear and logistic regressions models. Discriminative capacity of biomarkers was evaluated through calculating receiver operating characteristics (ROC) statistics. Results Plasma FT levels were significantly negatively correlated in clinical parameters, like HBI (r = -0.53, p < 0.05) (Fig. 1A). Other inflammatory biomarkers, like CRP, were also negatively correlated with plasma FT levels and were reduced in patients with active IBD (r = -0.43, p < 0.05) (Fig. 1B). Plasma FT levels accurately discriminated between CD patients with clinically quiescent (HBI < 5) and active disease (HBI ≥ 5) (AUC = 0.80, p = 0.02, Fig. 1C), better than fCal (AUC = 0.55, p = 0.83). Plasma FT were not significantly different for biochemically quiescent (CRP < 5 mg/l) and active (CRP ≥ 5mg/l) disease (AUC = 0.69, p = 0.20, Fig. 1D). Both Mayo and SES-CD scores, after adjusting for confounders, also exhibited a trend towards negative association with plasma FT levels (Fig. 1E). Figure 1 Conclusion Further completion of the trial will reveal whether systemic FT levels will reflect endoscopically observed disease activity, and this interim analysis shows strong correlations FT levels and parameters of clinically and biochemically active disease. Measuring systemic FTs in IBD may be a promising, minimally invasive strategy to monitor IBD disease activity. Funding None

P136 Blood-based biomarkers of type III collagen remodeling as surrogate markers of endoscopic disease activity in patients with Ulcerative Colitis

Abstract Background The chronic inflammation of Ulcerative Colitis (UC) causes excessive extracellular matrix (ECM) remodeling, resulting in clinical complications. Currently, endoscopic evaluation remains the gold standard method for determining disease activity. However, due to its invasiveness and accompanying patient discomfort, novel methods are wanted. Focusing on type III collagen, a major component of the intestinal ECM, we sought to investigate three blood-based neoepitope biomarkers of type III collagen formation, degradation, and fibrosis resolution as surrogate markers of disease activity. Methods Fifty-one patients with UC were scored endoscopically at weeks 0 (W0) and 24 (W24), according to the total Mayo score (TMS) and the UC Endoscopic Index of Severity (UCEIS). Three biomarkers of type III collagen remodeling, PRO-C3 (formation), C3M (MMP-9 degradation), and CTX-III (fibrosis resolution), were measured in the sera of patients and evaluated against the disease activity scores. Patients were grouped based on their disease activity score, and the biomarkers were evaluated by one-way ANOVA, correcting for multiple comparisons using Tukey (parametric data) or Dunn’s test (nonparametric). Results Grouping patients according to the TMS at W0, patients with severe disease had elevated serum C3M compared to patients with mild or moderate disease (p<0.05 and <0.01) (Figure 1A). Based on the UCEIS, patients with a severe disease presented with reduced CTX-III than moderate disease activity (p<0.05) (Figure 1C). While not statistically significant, a numerical trend of elevated C3M levels with increasing endoscopic disease activity was observed at W24 (Figure 1B). No statistically significant results were achieved evaluating C3M according to the UCEIS score, CTX-III according to the TMS or PRO-C3 according to the TMS and UCEIS score (Data not shown). Conclusion The serum levels of C3M were elevated in patients with UC at W0 when scoring their endoscopic disease activity using the TMS. At W24, a similar trend of elevated C3M with increasing disease activity could be observed. Using the UCEIS score, the CTX-III biomarker reflecting type III collagen resolution was reduced in patients with severe endoscopic disease. The data suggest an elevation of MMP-9 catalyzed type III collagen degradation with disease severity and reduced type III collagen resolution. The PRO-C3 biomarker provided no statistical value in the current study.

P177 C-reactive protein/albumin ratio: a novel biomarker for monitoring of the disease activity in Ulcerative Colitis patients

Abstract Background Fecal calprotectin (FC) is a reliable laboratory test for non-invasive assessment of disease activity in ulcerative colitis (UC) patients; it's high cost, absence of widespread availability and low patient adherence limits it's use as a potential surrogate for endoscopy. The association of higher C-reactive protein (CRP) and low albumin levels, both obtained from patient's sera, with disease acitivity in UC, is well established. C-reactive protein/albumin ratio (CAR) is suggested as a biomarker for evaluating disease activity in various inflammatory conditions. We aimed to evaluate association between CAR, FC, CRP and serum albumin values with disease activity in UC patients. Methods A single center, noninterventional retrospective chart review of adult UC patients treated with biologics at a tertiary center was performed. Routine clinical (stool frequency score – SFS, and rectal bleeding score – RBS), biochemical (CRP, serum albumin, FC), and endoscopic (Mayo Endoscopic Subscore – MES) findings were assessed prior to initiating biologics. Active UC was defined as SFS 2/3 + RBS 2/3 + MES 2/3. Differences between continuous variables were calculated using independent sample t-tests and Mann–Whitney U test. Sperman’s correlation and ROC curve analysis were carried out. The Z statistic was used to compare correlation coefficients and AUC. Results Total of 82 patients (52.2% females, mean age 40.3 ± 15.3 years, smokers 16.9%) with dominantly extensive UC (57.3%) were analysed. The CAR (0.175 vs 0.025; p=0.02) and FC (1363.5 vs 65.5; p=0.01) levels were significantly higher in active vs inactive UC patients. Positive correlation was observed between CAR (rs = 0.354, p = 0.01), FC (rs = 0.448, p = 0.001) and CRP (rs = 0.316, p = 0.005) with active UC. Although serum albumin (r's = - 0.093, p = 0.532) negatively correlated with disease activity it didn't reach statistical significance. There was no statistically significant difference between CAR and FC correlation coefficients. The area under the curve (AUC) for the diagnosis of active UC was 0.896 (SE: 0.058; 95% CI 0.73 - 0,983, p=0.015) and 0.994 (SE: 0.009; 95% CI 0.98 - 1, p=0.001) for CAR and FC, respectively. Although AUC for FC was higher compared to CAR it didn’t reach statistical significance (p = 0.1). The cut-off value associated with the active UC for CAR was 0.06 (sensitivity 77,2%, specificity 100%), and 120 mcg/g for FC (sensitivity 97.6%, specificity 100%). Conclusion There is good correlation between CAR and clinical as well as endoscopic disease activity in patients with UC, comparable to FC. CAR could be offered as a cheap and practical biomarker for detection of active UC disease.

Predictive models for endoscopic disease activity in patients with ulcerative colitis: Practical machine learning-based modeling and interpretation.

Endoscopic disease activity monitoring is important for the long-term management of patients with ulcerative colitis (UC), there is currently no widely accepted non-invasive method that can effectively predict endoscopic disease activity. We aimed to develop and validate machine learning (ML) models for predicting it, which are desired to reduce the frequency of endoscopic examinations and related costs. The patients with a diagnosis of UC in two hospitals from January 2016 to January 2021 were enrolled in this study. Thirty nine clinical and laboratory variables were collected. All patients were divided into four groups based on MES or UCEIS scores. Logistic regression (LR) and four ML algorithms were applied to construct the prediction models. The performance of models was evaluated in terms of accuracy, sensitivity, precision, F1 score, and area under the receiver-operating characteristic curve (AUC). Then Shapley additive explanations (SHAP) was applied to determine the importance of the selected variables and interpret the ML models. A total of 420 patients were entered into the study. Twenty four variables showed statistical differences among the groups. After synthetic minority oversampling technique (SMOTE) oversampling and RFE variables selection, the random forests (RF) model with 23 variables in MES and the extreme gradient boosting (XGBoost) model with 21 variables in USEIS, had the greatest discriminatory ability (AUC = 0.8192 in MES and 0.8006 in UCEIS in the test set). The results obtained from SHAP showed that albumin, rectal bleeding, and CRP/ALB contributed the most to the overall model. In addition, the above three variables had a more balanced contribution to each classification under the MES than the UCEIS according to the SHAP values. This proof-of-concept study demonstrated that the ML model could serve as an effective non-invasive approach to predicting endoscopic disease activity for patients with UC. RF and XGBoost, which were first introduced into data-based endoscopic disease activity prediction, are suitable for the present prediction modeling.

Leucine-Rich Alpha-2 Glycoprotein Is a Reliable Serum Biomarker for Evaluating Clinical and Endoscopic Disease Activity in Inflammatory Bowel Disease.

Leucine-rich alpha-2 glycoprotein (LRG) is a novel serum biomarker for inflammation in inflammatory bowel disease (IBD). This prospective study aimed to compare the value of LRG with C-reactive protein (CRP) and fecal calprotectin for evaluating clinical and endoscopic disease activity in patients with IBD. At entry, clinical and endoscopic disease activity was assessed in 267 patients with IBD (ulcerative colitis [UC] 203; Crohn's disease [CD] 64), and the levels of LRG, CRP and fecal calprotectin were measured. The accuracy of the biomarkers for the detection of clinical and endoscopic disease activity was determined by the area under the receiver operating characteristic curve. Leucine-rich alpha-2 glycoprotein showed a significant relationship with the clinical and endoscopic severity in both UC and CD (both diseases, P < .0001). In the clinical assessment of UC, the accuracy of LRG was significantly higher than that of CRP (0.73 vs 0.63; P < .001). In the endoscopic assessment of UC, the accuracy of LRG was significantly higher than that of CRP (P = .01), but it was significantly lower than that of fecal calprotectin (P = .009; LRG, 0.80; CRP, 0.72; fecal calprotectin, 0.91). In the clinical and endoscopic assessment of CD, the accuracy was not significantly different between the biomarkers (clinical activity: LRG, 0.71; CRP, 0.64; fecal calprotectin, 0.66; in endoscopic activity: LRG, 0.79; CRP, 0.78; fecal calprotectin, 0.81). Leucine-rich alpha-2 glycoprotein is a reliable serum biomarker for the assessment of clinical and endoscopic disease activity in patients with IBD. It can be an alternative to CRP for the assessment of UC.

P127 Type I collagen degradation fragments (C1M) and human neutrophil elastase-derived fragments of calprotectin (CPa9-HNE) reflect biochemical and endoscopic disease activity in patients with Inflammatory Bowel Disease

Abstract Background Crohn’s disease (CD) and ulcerative colitis (UC) are characterized by intestinal inflammation and increased extracellular matrix (ECM) remodeling, which are key pathophysiological mechanisms in patients with IBD and highly related to mucosal damage. Alterations in intestinal ECM turnover as well as macrophage and neutrophil activity may be reflected by secreted products that are released into the systemic circulation. In this study, we aimed to investigate associations between serum biomarkers of neutrophil activity (serum calprotectin) and collagen degradation (mucosal damage), and disease activity in patients with IBD. Methods Serological biomarkers of collagen formation (PRO-C3, PRO-C4, PRO-C6), matrix metalloproteinase (MMP)-mediated collagen degradation (C1M, C3M, C4M, C4G, C6Ma3) and intestinal inflammation (VICM [macrophage activity], human neutrophil elastase-derived fragment of calprotectin (CPa9-HNE [serum calprotectin, neutrophil activity]) were measured using Protein FingerPrint assay (PFA) technology in 100 patients with IBD (CD: n=44; UC: n=56). Biochemical disease activity was assessed using C-reactive protein (CRP) levels and available faecal calprotectin (FCal) levels. Endoscopic disease activity was determined using the Simple Endoscopic Score for CD (SES-CD) and Mayo endoscopic subscore for UC. Results C1M strongly associated with elevated CRP levels (defined as &amp;gt;5mg/L, P&amp;lt;0.001) in patients with IBD and significantly associated with faecal calprotectin levels in patients with UC (Spearman’s ρ=0.75, P&amp;lt;0.001). In patients with CD, C1M reasonably discriminated between patients with mild and moderate-to-severe endoscopic disease activity (AUC=0.73, P=0.01), whereas this discrimination was more subtle in patients with UC (AUC=0.68, P=0.08). CPa9-HNE levels were significantly increased in patients with elevated CRP levels (P=0.002 for both CD and UC) and associated best with faecal calprotectin levels in patients with CD compared with UC (CD: ρ=0.43, P=0.06; UC: ρ=0.20, P=0.45). Finally, CPa9-HNE levels were able to discriminate between mild and moderate-to-severe endoscopic disease activity in patients with CD (AUC=0.75, P&amp;lt;0.01). Conclusion C1M and CPa9-HNE levels associate with biochemical (CRP, FCal) and endoscopic disease activity in patients IBD, where C1M demonstrated higher accuracy in UC and CPa9-HNE appeared to be more useful in CD in this cohort. Therefore, C1M and CPa9-HNE could serve as surrogate biomarkers for the assessment of disease activity in patients with UC and CD, respectively. Our results should be validated in additional prospective, larger patient cohorts to corroborate these findings.

P497 The value of endoscopic healing index monitoring for guiding infliximab dosing in patients with Crohn’s disease

Abstract Background The endoscopic healing index (EHI) is a novel multi-protein serum biomarker test developed and validated to assess endoscopic disease activity in patients with Crohn’s disease (CD). Evidence for the use of EHI to guide decision-making during infliximab (IFX) treatment remains scarce. Therefore, we aimed to characterise the relationships between IFX dose, serum IFX concentrations, EHI, and endoscopic remission (ER). Methods Data were obtained from 118 biologic naïve adult patients with CD enrolled in the phase 4 TAILORIX trial (EudraCT 2011 003038 14). All patients had confirmed active CD at baseline based on clinical, biological, and endoscopic criteria. IFX and EHI (scores ranging from 0–100) were measured using a homogenous mobility shift assay (HMSA) and immunoassay, respectively (Prometheus Laboratories). First, the previously published population pharmacokinetic (popPK) model of the TAILORIX study population was revisited to describe the HMSA data. The effect of EHI, faecal calprotectin (FC), C-reactive protein (CRP), and serum albumin (ALB) on IFX clearance was evaluated. Next, a minimal continuous-time Markov model was developed to describe the time course of EHI within patients. EHI was considered as a three-stage ordinal variable (scores 0–19, 20–49, and 50–100) with the lowest score stage (0–19) indicative of ER. The course-modifying effect of IFX on EHI was assessed. Finally, a generalised linear model was used to describe the relationship between EHI and the probability of attaining ER (Simple Endoscopic Score for CD [SES-CD] ≤2). The predictive ability of EHI for ER was compared with that of FC, CRP, ALB, and IFX using a receiver operating characteristic (ROC) curve analysis. Results The revisited two-compartment popPK model described the IFX data with adequate descriptive and predictive accuracies. EHI, FC, CRP, and ALB at week (w)0 were not found to explain interpatient variability in IFX clearance. In contrast, higher IFX at w14 was associated with a higher probability of achieving EHI &amp;lt;20 at w14 (Figure 1). The probability of attaining EHI &amp;lt;20 at w14 was predicted to increase more than four-fold when IFX at w14 was targeted at 10 mg/L instead of 5 mg/L (Table 1). EHI and FC equally well predicted the probability of attaining ER at the same time point (Figure 2, Table 2). Conclusion EHI, FC, ALB, and CRP at w0 should not be considered for a priori IFX dose optimisation. Nevertheless, a posteriori IFX dose optimisation (based on IFX concentrations measurements) towards a predefined IFX concentration at w14 may lead to lower post-induction EHI scores and thus improved ER rates. An IFX target of 10 mg/L at w14 is associated with four-fold higher normalisation of EHI as compared to the commonly used target of 5 mg/L.

P149 Ulcerative colitis patients with high calprotectin levels should undergo endoscopy within 7 days for therapeutic decision

Abstract Background Fecal calprotectin (FC) has considered as a useful surrogate marker to predict which patients with ulcerative colitis (UC) are in endoscopic activity. FC has to be collected at the time of endoscopy for more accurate correlation between FC and endoscopic disease activity. In real practice, however, both tests cannot be easy to perform at the same time. Therefore, the aim of this study was to evaluate the optimal time interval for the correlation between FC and endoscopic disease activity in UC patients. Methods We analysed retrospectively 103 cases (79 patients) that was performed FC measurement and endoscopy within 3 months. FC quantitative tests was defined as normal (&amp;lt;100 μg/g), mild (100–200, 100–250 or 100–300 μg/g), and moderate to severe activity (&amp;gt;200, &amp;gt; 250, or &amp;gt; 300 μg/g). Endoscopic activity was graded using the Mayo endoscopic subscore (MES). After assessing concordance between FC level and MES, we use the youden index method to estimate the optimal time interval between both tests using the receiver operator curves (ROCs). Results Among 79 UC patients, 64.5% (51/79) were male. The mean FC level was 673.6 ± 1054 μg/g. The mean interval between FC measurement and endoscopy was 13.8 ± 22.7 days. FC levels and MES were positively correlated (r = 0.473, p &amp;lt; 0.001). Using a ROC curve with a cut off value of FC 200 μg/g, the optimal cut-off of the time interval for separation of non-correlation and correlation between FC level and MES was 7 days with a sensitivity of 74.4% and a specificity of 50.0% (AUC 0.6032; 95% CI 0.4779–0.6896). Similarly, using ROC curves with a cut off value of FC 250 or 300 μg/g as a standard for dividing mild and moderate, the optimal cut-off of the time interval were all 5.5 days (FC 250, sensitivity 71.7%, specificity 49.1, AUC 0.5862, 95% CI 0.4728–0.6884; FC 300, sensitivity 69.6%, specificity 47.4, AUC 0.5549, 95% CI 0.4668–0.6513). Conclusion FC level within 7 days could reflect endoscopic disease activity in patients with UC. In patients with high-level FC more than 200 μg/g, endoscopic evaluation for therapeutic decision making should be performed within a maximum of 7 days.

Tu1745 – Correlation of Fecal Calprotectin and C-Reactive Protein Concentrations with Clinical Outcomes and Endoscopic Disease Activity in Patients with Ulcerative Colitis Receiving Induction Therapy with Etrasimod

Tu1745 – Correlation of Fecal Calprotectin and C-Reactive Protein Concentrations with Clinical Outcomes and Endoscopic Disease Activity in Patients with Ulcerative Colitis Receiving Induction Therapy with Etrasimod

P166 A combined set of four serum inflammatory biomarkers reliably predicts endoscopic disease activity in inflammatory bowel disease

Background Mucosal healing is the ultimate treatment goal in inflammatory bowel disease (IBD). Endoscopic examination is the gold standard to determine disease activity in IBD, as routine activity measures, such as C-reactive protein (CRP), faecal calprotectin and clinical disease indices are inconsistent in representing luminal disease activity. Therefore, there is a great need for non-invasive biomarkers to assess mucosal inflammation. The aim of this study was to build an accurate prediction model of endoscopic disease activity in patients with quiescent and active IBD, based on a combination of serum inflammatory biomarkers. Methods Serum concentrations of 10 inflammatory biomarkers were analysed in 118 IBD patients (64 Crohn’s disease (CD), 54 ulcerative colitis (UC)) prior to biological treatment and 20 healthy controls. In 71 IBD patients, endoscopic disease activity was assessed by the Simple Endoscopic Score for CD (SES-CD) and Mayo endoscopic subscore for UC. Nonparametric ROC estimation with bootstrap inference was used to establish the best combination of inflammatory biomarkers predicting endoscopic disease activity. Results Six (6) inflammatory biomarkers (serum amyloid A (SAA), Eotaxin-1, IL-6, IL-8, IL-17A and TNF-α) all individually showed better prediction of IBD disease activity compared with routine measures (CRP, faecal calprotectin and HBI/SCCAI scores). The best combination of predictive inflammatory biomarkers consisted of serum SAA, IL-6, IL-8 and Eotaxin-1, showing an optimism-adjusted area under the ROC curve of 0.84 (95% CI: 0.73–0.94, P < 0.0001), which predicted significantly better (P = 0.002) than serum CRP levels with an AuROC of 0.57 (95% CI: 0.43–0.72, P = 0.32). The resulting combined calculated probability had a maximum sensitivity of 90.7% and specificity of 68.4% in correctly classifying IBD patients into the low and high endoscopic disease activity category (Youden’s J statistic = 0.58). Conclusions The combination of SAA, IL-6, IL-8 and Eotaxin-1 is superior over routine measures in predicting endoscopic disease activity in IBD. Serum inflammatory biomarkers are valuable tools for monitoring intestinal inflammation and guiding therapeutic decisions.

DOP64 Minimal additional benefits in adding faecal haemoglobin to faecal calprotectin in predicting endoscopic disease activity in patients with inflammatory bowel disease

DOP64 Minimal additional benefits in adding faecal haemoglobin to faecal calprotectin in predicting endoscopic disease activity in patients with inflammatory bowel disease

Novel computer-assisted diagnosis system for endoscopic disease activity in patients with ulcerative colitis

Evaluation of endoscopic disease activity for patients with ulcerative colitis (UC) is important when determining the treatment of choice. However, endoscopists require a certain period of training to evaluate the activity of inflammation properly, and interobserver variability exists. Therefore, we constructed acomputer-assisted diagnosis (CAD) system using a convolutional neural network (CNN) and evaluated its performance using a large dataset of endoscopic images from patients with UC. A CNN-based CAD system was constructed based on GoogLeNet architecture. The CNN was trained using 26,304 colonoscopy images from a cumulative total of 841 patients with UC, which were tagged with anatomic locations andMayo endoscopic scores. The performance of the CNN in identifying normal mucosa (Mayo 0) and mucosal healing state (Mayo 0-1) was evaluated in an independent test set of 3981 images from 114 patients with UC, by calculating the areas under the receiver operating characteristic curves (AUROCs). In addition, AUROCs in the right side of the colon, left side of the colon, and rectum were evaluated. The CNN-based CAD system showed a high level of performance with AUROCs of 0.86 and 0.98 to identify Mayo 0 and 0-1, respectively. The performance of the CNN was better for the rectum than for the right side and left side of the colon when identifying Mayo 0 (AUROC= 0.92, 0.83, and 0.83, respectively). The performance of the CNN-based CAD system was robust when used to identify endoscopic inflammation severity in patients with UC, highlighting its promising role in supporting less-experienced endoscopists and reducing interobserver variability.

P548 Limited clinical value in assessing the distribution of endoscopic disease activity in patients with ulcerative colitis

P548 Limited clinical value in assessing the distribution of endoscopic disease activity in patients with ulcerative colitis

Association between serum adalimumab concentrations and endoscopic disease activity in patients with Crohn's disease.

The serum trough level of adalimumab (ADA) associated with mucosal healing (MH) remains unclear. Our objective was to determine the association between ADA trough levels and the endoscopic activity in Crohn's disease. This was a cross-sectional study including 42 patients with Crohn's disease. Endoscopic activity was assessed using the modified Rutgeerts scoring system. The primary outcome was mucosal healing, and the secondary outcomes were serum levels of C-reactive protein and albumin. Endoscopic disease activity negatively correlated with serum ADA trough levels (Spearman's rank correlation coefficient (ρ) = -0.42, P < 0.01). MH was achieved in 14 of 42 patients (33.3%). Serum ADA trough levels were significantly higher in the MH group than in the no-MH group (ADA mean trough level, 11.7 vs 7.5 µg/mL). The proportion of patients with ADA as the first biologic was significantly higher in the MH group than in the no-MH group (85.7% vs 53.5%, P = 0.04). The ADA trough levels that were best associated with normal C-reactive protein and albumin levels were 5.57 µg/mL (odds ratio [OR] 16.0, specificity 0.80) and 6.95 µg/mL (OR 9.2, specificity 0.81), respectively. The ADA trough level that was best associated with MH was 7.9 µg/mL (OR 13.5, specificity 0.86). The endoscopic disease activity was significantly higher in the patients with ADA as the second biologic as compared with those with ADA as the first biologic (P < 0.05). Mucosal healing requires higher ADA trough levels, compared with those required to normalization of routine clinical markers.

The Correlation of Serum IL-12B Expression With Disease Activity in Patients With Inflammatory Bowel Disease.

Genetic variants in IL12B, encoding the p40 subunit common in interleukin-12 (IL-12) and interleukin-23, were identified as the susceptibility loci for inflammatory bowel disease (IBD). This study aimed to identify the correlation of serum IL-12B expression with disease activity in patients with IBD and evaluate the possibility of IL-12B as a biomarker for assessing inflammatory status in IBD.A total of 102 patients with IBD, including 38, 32, and 32 patients with Crohn's disease (CD), ulcerative colitis (UC), and intestinal Behçet's disease (intestinal BD), respectively, were included. The clinical and laboratory data from the patients were collected at the time of serum IL-12B measurement. Serum IL-12B levels were measured using an enzyme-linked immunosorbent assay.The median IL-12B levels in patients with CD, UC, and intestinal BD were significantly higher than those in controls (1.87, 2.74, and 2.73 pg/mL, respectively, vs. 1.42 pg/mL, all P <0.05). IL-12B concentrations were associated with disease activity in patients with UC and intestinal BD but not in those with CD. IL-12B levels were increased with increasing disease activity in patients with UC (P <0.001). Likewise, patients with active intestinal BD had higher IL-12B levels than those without active disease (P = 0.008). IL-12B levels were correlated with the endoscopic disease activity of UC (P = 0.002) and intestinal BD (P = 0.001) but not that of CD.Serum IL-12B levels were significantly correlated with clinical and endoscopic disease activity in patients with UC and intestinal BD, suggesting its potential use as a biomarker for assessing disease activity in these patients.

Tu1929 Association of Macro/Micro Nutrients With Endoscopic Disease Activity in Patients With Inflammatory Bowel Disease Suggests Possible Protective Role for Dietary Components

Tu1929 Association of Macro/Micro Nutrients With Endoscopic Disease Activity in Patients With Inflammatory Bowel Disease Suggests Possible Protective Role for Dietary Components

P270. Association of macro/micro nutrients with endoscopic disease activity in patients with inflammatory bowel disease suggests possible protective role for dietary components

P270. Association of macro/micro nutrients with endoscopic disease activity in patients with inflammatory bowel disease suggests possible protective role for dietary components

Predicting Endoscopic Disease Activity in Crohn's Disease: A New and Validated Noninvasive Disease Activity Index (The Utrecht Activity Index).

Mucosal healing is presently considered one of the primary goals in treatment of Crohn's disease (CD), but this can only be confirmed by endoscopy. We aimed to design and validate a new disease activity index based on a combination of clinical characteristics and readily available laboratory parameters, which reliably predicts the presence and severity of endoscopic disease activity in patients with CD. Thirteen clinical characteristics and laboratory variables were selected for analysis. Endoscopic disease activity was assessed by the Crohn's disease Endoscopic Index of Severity. A linear regression model was based on 93 ileocolonoscopies performed in 82 patients with CD and internally validated by bootstrap resampling. Subsequently, the newly developed model was validated in a cohort of 99 patients. The number of liquid stools during 1 day × 0.25 + C-reactive protein (in milligrams per liter) × 0.1 + platelet count (× 10(9)/L) × 0.01 + fecal calprotectin (in milligrams per liter) × 0.001 - mean platelet volume (in femtoliters) × 0.2 optimally predicted the severity of endoscopic disease activity (bootstrap adjusted R2 = 0.50). The model demonstrated good agreement in the external validation (r = 0.7), especially for (ileo)colonic CD (r = 0.8). Using receiver operator characteristic statistics, a cutoff point of 3 on the new index indicated endoscopic disease activity with a sensitivity of 80% and a specificity of 92%. This newly developed, noninvasive, index was found to reliably predict endoscopic disease activity in patients with CD. This tool can facilitate clinical decision making and might prove valuable in clinical trials.

Correlation of Intestinal Tissue Anti-TNF Drug Levels with Endoscopic Disease Activity in Patients with Inflammatory Bowel Disease: The ATLAS Study

Correlation of Intestinal Tissue Anti-TNF Drug Levels with Endoscopic Disease Activity in Patients with Inflammatory Bowel Disease: The ATLAS Study

Neopterin Is a Novel Reliable Fecal Marker as Accurate as Calprotectin for Predicting Endoscopic Disease Activity in Patients with Inflammatory Bowel Diseases

Fecal biomarkers have emerged as an important tool for assessing and monitoring disease activity in patients with inflammatory bowel diseases (IBDs). We performed a prospective head-to-head comparison of the diagnostic accuracy of both fecal calprotectin (fCal) and neopterin (fNeo), and serum C-reactive protein in predicting endoscopic disease severity in patients with IBD. A total of 133 consecutive patients with IBD (78 Crohn's disease [CD] and 55 ulcerative colitis [UC]) undergoing a colonoscopy provided fecal samples for the measurement of fCal and fNeo concentrations and a blood sample for the serum C-reactive protein measurement. Endoscopic disease activities were scored independently according to the Simple Endoscopic Score for CD in patients with CD and to the Rachmilewitz Index in patients with UC. The respective performances of the fecal markers with respect to endoscopic disease severity were assessed by computing correlations, sensitivities, specificities, and overall accuracies at adjusted cutoffs and also test operating characteristics. The fCal and fNeo concentrations differed significantly in clinically and endoscopically active IBD when compared with those in patients with inactive disease. Both fCal and fNeo concentrations correlated closer with endoscopic scores in UC (r = 0.75 and r = 0.72, respectively; P < 0.0001 for both) than in CD (r = 0.53 and r = 0.47, respectively; P < 0.0001 for both). Using cutoffs of 250 μg/g for fCal and 200 pmol/g for fNeo, both fecal markers had similar overall accuracies to predict endoscopic activity in patients with CD (74%) and also a higher and similar accuracies (88% and 90%, respectively) in patients with UC, whereas accuracies of C-reactive protein were slightly lower in patients with CD and UC. The fNeo is a novel reliable surrogate biomarker with the potential to identify patients with IBD with active mucosal lesions and represents an alternative marker as accurate as fCal to predict and monitor the severity of mucosal damages in patients with IBD.