Crohn's Disease Endoscopic Index Of Severity Research Articles

Stem Cells as Treatment in Inflammatory Bowel Disease

Background: The Autologous Stem Cell Transplantation International Crohn’s Disease (ASTIC) trial is a randomised controlled evaluation of the proposition that immunoablation and haemopoietic stem cell transplantation improves the course of Crohn’s disease. Recruitment of all 48 patients in the trial will be completed in early 2012 and the results to date are descriptively presented here. Methods: Patients with an impaired quality of life due to active Crohn’s disease, despite the administration of at least 3 immunosuppressive agents, all received mobilisation treatment (cyclophosphamide 4 g/m² over 2 days followed by recombinant human granulocyte colony stimulating factor (filgrastim) 10 µg/kg daily before randomisation to immediate (after 1 month) or delayed (after 1 year) immunoablation and stem cell transplantation. The conditioning regime was cyclophosphamide 50 mg/kg/day for 4 days, anti-thymocyte globulin 2.5 mg/kg/day and methylprednisolone 1 mg/kg on days 3–5. The bone marrow was reconstituted by the infusion of an unselected graft of 3–8 × 10⁶/kg CD34-positive stem cells. Results were compared 1 year after mobilisation alone or after transplantation. Results: Twelve months after stem cell transplantation (early or delayed) the Crohn’s Disease Activity Index (CDAI) fell from 324 (median, interquartile range 229–411) to 161 (85–257, n = 17) compared to 351 (287–443) to 272 (214–331) following mobilisation alone (n = 11). Six patients had a normal CDAI after transplantation versus 1 after mobilisation. C-reactive protein fell from 16.6 (6.7–32.0) to 6.5 (3.5–12.5) mg/l versus 14 (8.0–27.0) to 9.0 (2.0–23.4) mg/l following mobilisation alone. The Crohn’s Disease Endoscopic Index of Severity (CDEIS) (aggregate for upper and lower endoscopy) fell from 18 (10–25) to 5 (1–11) following transplantation versus 14 (12–16) to 9 (4–22) following mobilisation. Three patients achieved the goal of a normal CDAI, no drug therapy and normal upper and lower endoscopy 1 year after transplantation, but so did 1 patient following mobilisation alone. Serious adverse events were common (n = 100 to date) with 42 infective episodes requiring or prolonging hospitalisation, following both mobilisation and conditioning and transplantation. There were 7 episodes of viral (re)activation. Temporary flare of Crohn’s disease activity or a need for surgery occurred in 8 patients. Conclusions: Immunoablation and haemopoietic stem cell transplantation appear to be an effective treatment for some patients with Crohn’s disease, although full results will be required for a firm conclusion. The risks are significant, making it potentially suitable for only a limited number of patients. Data from the whole trial will be needed to judge whether mobilisation alone has any benefits.

Development of Three Practical Indices for Mucosal Healing Among Patients With Moderate to Severe Crohnʼs Disease

Healing of the intestinal mucosa is considered a valid and important metric of improvement in Crohn's disease (CD). However, a patient must undergo an endoscopy to verify the presence of mucosal ulceration. Regular monitoring using endoscopy is challenging owing to its expensive and intrusive nature. There are currently no easily accessible proxy measures for identifying patients who are likely to have achieved mucosal healing (MH) in CD. The practical MH indices were developed using intent-to-treat (ITT) patient-level data from the EXTend the Safety and Efficacy of Adalimumab Through ENDoscopic Healing (EXTEND) trial (160 mg adalimumab at Week 0, 80 mg at Week 2, and randomized to 40 mg every other week or placebo at Week 4). Each index corresponds to 1 of 3 mucosal healing measures: Simple Endoscopic Score for CD (SES-CD) <5, CD Endoscopic Index of Severity (CDEIS) score ≤4.24, and observed MH based on a review committee opinion. For each measure, a logistic regression model was developed to predict MH at Week 12 using demographic, laboratory, and CD severity characteristics. Important predictors were selected using the Least Absolute Shrinkage and Selection Operator (LASSO) procedure, which identifies a parsimonious model while retaining predictive accuracy. These 3 indices, named as SES-CD Based Index, CDEIS Based Index, and Observed MH Based Index, were evaluated using the accuracy (c-statistic), sensitivity, and specificity measures. Important factors associated with MH were similar across the 3 indices (Table). The performance of each index was also evaluated and listed in the table. Platelet count, CRP, and CDAI (number of liquid or very soft stools) are the common factors associated with MH across all 3 indices. The accuracy rates suggest the practical indices may be a clinically useful guide for identifying patients who are likely or unlikely to have achieved MH.

Certolizumab Pegol Plasma Concentrations and Endoscopic and Clinical Outcomes in Crohnʼs Disease: A Post Hoc Analysis of the MUSIC Trial: Presidential Poster

Purpose: The MUSIC trial (NCT00297648) demonstrated that certolizumab pegol (CZP) treatment in patients (pts) with active Crohn's disease (CD) and severe endoscopic disease showed improvement in both endoscopic and clinical outcomes as early as Wk 10.1 This post hoc analysis of data from the MUSIC trial evaluates the associations between serum plasma CZP concentrations and endoscopic and clinical outcomes at Wk 10. Methods: Adult pts (N=89) with active CD for ≥3 months and significant endoscopic lesions (ulcerations in ≥2 intestinal segments with CD Endoscopic Index of Severity [CDEIS] score ≥8) received open-label subcutaneous CZP 400 mg at Wks 0, 2, and 4 (induction dose) and then every 4 wks until Wk 54. CZP plasma concentrations were collected at Wk 8 (trough level) and stratified by quartiles. Rates of endoscopic response (CDEIS decrease from baseline >5) and remission (CDEIS <6) and of clinical response (CD Activity Index [CDAI] decrease from baseline ≥100) and remission (CDAI score ≤150) were determined at Wk 10. Results: A total of 45 pts received CZP 400 mg induction at 0, 2, and 4 wks and had an available CZP trough measurement at Wk 8 and response/remission status at Wk 10. At Wk 10, there was a significant difference between the CZP concentration quartiles regarding CDEIS response and remission rates (p=0.0016 and p=0.0302, respectively) (Table). A similar trend at Wk 10 was observed in clinical efficacy with a significant difference between the CZP concentration quartiles regarding CDAI remission (p=0.0378), while CDAI response did not achieve statistical significance (p=0.2993).Table: Proportions of pts achieving endoscopic and clinical outcomes by CZP plasma concentration quartiles (Q)Conclusion: This post hoc analysis of the MUSIC study identifies an association between endoscopic response and remission and clinical remission and higher plasma concentrations of CZP following standard induction therapy. Further prospective evaluation of the correlation between CZP plasma concentration and both endoscopic and clinical outcomes is warranted.

Dynamic contrast-enhanced MRI in patients with luminal Crohn's disease

ObjectivesTo prospectively assess dynamic contrast-enhanced (DCE-)MRI as compared to conventional sequences in patients with luminal Crohn's disease. MethodsPatients with Crohn's disease undergoing MRI and ileocolonoscopy within 1 month had DCE-MRI (3T) during intravenous contrast injection of gadobutrol, single shot fast spin echo sequence and 3D T1-weighted spoiled gradient echo sequence, a dynamic coronal 3D T1-weighted fast spoiled gradient were performed before and after gadobutrol. Maximum enhancement (ME) and initial slope of increase (ISI) were calculated for four colon segments (ascending colon+coecum, transverse colon, descending colon+sigmoid, rectum) and (neo)terminal ileum. C-reactive protein (CRP), Crohn's disease activity index (CDAI), per patient and per segment Crohn's disease endoscopic index of severity (CDEIS) and disease duration were determined. Mean values of the (DCE-)MRI parameters in each segment from each patient were compared between four disease activity groups (normal mucosa, non-ulcerative lesions, mild ulcerative and severe ulcerative disease) with Mann–Whitney test with Bonferroni adjustment. Spearman correlation coefficients were calculated for continuous variables. ResultsThirty-three patients were included (mean age 37 years; 23 females, median CDEIS 4.4). ME and ISI correlated weakly with segmental CDEIS (r=0.485 and r=0.206) and ME per patient correlated moderately with CDEIS (r=0.551). ME was significantly higher in segments with mild (0.378) or severe (0.388) ulcerative disease compared to normal mucosa (0.304) (p<0.001). No ulcerations were identified at conventional sequences. ME correlated with disease duration in diseased segments (r=0.492), not with CDAI and CRP. ConclusionsDCE-MRI can be used as a method for detecting Crohn's disease ulcerative lesions.

OC-043 Controlled trial of immunoablation and autologous haemopoetic stem cell transplantation in crohn's disease: interim report on behalf of the ASTIC trialists

IntroductionThe Autologous Stem Cell Transplantation International Crohn's Disease (ASTIC) Trial is a randomised controlled evaluation of the proposition that immunoablation and hemopoietic stem cell transplantation improves the course of Crohn's...

Endoscopic improvement of mucosal lesions in patients with moderate to severe ileocolonic Crohn's disease following treatment with certolizumab pegol

ObjectiveTo evaluate the efficacy of certolizumab pegol (CZP) in improving endoscopic lesions in patients with active ileocolonic Crohn's disease (CD).MethodsThis phase IIIB multicentre open-label clinical trial enrolled 89 adult patients...

Su1925 Development of Three Practical Indices for Mucosal Healing Among Patients With Moderate to Severe Crohn's Disease

s of the 7th Congress of ECCO the European Crohn’s and Colitis Organisation S3 OP05 Development of three practical indices for mucosal healing among patients with moderate to severe Crohn’s disease W. Sandborn1, R. Panaccione2, J.-F. Colombel3, E. Louis4 *, M. Yang5, R. Thakkar5, J. Chao5, P. Mulani5. 1University of California, San Diego, La Jolla, United States, 2University of Calgary, Director, Inflammatory Bowel Disease Clinic, Calgary, Canada, 3Centre Hospitalier Universitaire de Lille, Hopital Claude Huriez, Lille, France, 4University of Liege and CHU Liege, Department of Gastroenterology, Liege, Belgium, 5Abbott Laboratories, Illinois, United States Background: Healing of the intestinal mucosa is considered a valid and important metric of improvement in Crohn’s disease (CD). However, a patient must undergo an endoscopy to verify the presence of mucosal ulceration. Regular monitoring using endoscopy is challenging owing to its expensive and intrusive nature. There are currently no easily accessible proxy measures for identifying patients who are likely to have achieved mucosal healing (MH) in CD. Methods: The practical MH indices were developed using intent-to-treat (ITT) patient-level data from the EXTend the Safety and Efficacy of Adalimumab Through ENDoscopic Healing (EXTEND) trial (160mg adalimumab at Week 0, 80mg at Week 2, and randomised to 40mg every other week or placebo at Week 4). Each index corresponds to 1 of 3 mucosal healing measures: Simple Endoscopic Score for CD (SES-CD) <5, CD Endoscopic Index of Severity (CDEIS) score 4.24, and observed MH based on a review committee opinion. For each measure, a logistic regression model was developed to predict MH at Week 12 using demographic, laboratory, and CD severity characteristics. Important predictors were selected using the Least Absolute Shrinkage and Selection Operator (LASSO) procedure, which identifies a parsimonious model while retaining predictive accuracy. These 3 indices, named as SES-CD Based Index, CDEIS Based Index, and Observed MH Based Index, were evaluated using the accuracy (c-statistic), sensitivity, and specificity measures. Results: Important factors associated with MH were similar across the 3 indices (Table). The performance of each index was also evaluated and listed in the table. Name Components of Each Index (important factors associated with MH) Accuracy (c-statistic) Sens (%) Spec (%)

Introduction to the Feature Section on “Crohn’s disease activity: MRI assessment and clinical implications”

The purpose of this feature section is to provide a clinical–radiological update on an emerging topic of gastrointestinal imaging, the assessment of Crohn’s Disease (CD) activity with MRI. The term ‘‘Crohn’s Disease Activity’’ is widely used by gastroenterologists to evaluate the degree of intestinal inflammation. Currently, several clinical, biological, endoscopic, and histological indexes are used in the clinical practice to quantify inflammation of CD, including the widely used Crohn’s disease activity index (CDAI) and the Crohn’s disease endoscopic index of severity (CDEIS). Similarly, several imaging modalities, including contrast-enhanced ultrasonography, contrast-enhanced CT and MRI, are variably used for detecting the main signs of intestinal inflammation in CD. The growing interest shown by gastroenterologists in the assessment of CD activity is related to the need of monitoring the evolution of the disease and the therapeutic efficacy of both traditional and new biological treatments.

Fecal calprotectin is a surrogate marker for endoscopic lesions in inflammatory bowel disease

Fecal calprotectin is a marker of inflammation in inflammatory bowel disease (IBD). Since mucosal healing has become a goal of treatment in IBD we examined how reliably calprotectin levels reflect mucosal disease activity. In all, 126 IBD patients and 32 irritable bowel syndrome (IBS) patients needing colonoscopy delivered a sample of feces prior to the start of bowel cleansing. Besides collection of symptom scores and blood tests, experienced endoscopists recorded the Simple Endoscopic Score for Crohn's Disease (SES-CD) and the Crohn's Disease Endoscopic Index of Severity (CDEIS) in Crohn's disease (CD) patients and the Mayo endoscopic score in ulcerative colitis (UC) patients. Stool samples were shipped for central calprotectin PhiCal Assay (enzyme-linked immunosorbent assay [ELISA]). Correlation analysis was done with Pearson statistics. The median (interquartile range [IQR]) fecal calprotectin levels were 175 (44-938) μg/g in CD, 465 (61-1128) μg/g in UC, and 54 (16-139) μg/g in IBS. Correlations were significant with endoscopic disease scores in both CD and in UC. Using ROC statistics, a cutoff value of 250 μg/g indicated the presence of large ulcers with a sensitivity of 60.4% and a specificity of 79.5% (positive predictive value [PPV] 78.4%, negative predictive value [NPV] 62.0%) in CD. Levels ≤ 250 μg/g predicted endoscopic remission (CDEIS ≤ 3) with 94.1% sensitivity and 62.2% specificity (PPV 48.5%, NPV 96.6%). In UC, a fecal calprotectin >250 μg/g gave a sensitivity of 71.0% and a specificity of 100.0% (PPV 100.0%, NPV 47.1%) for active mucosal disease activity (Mayo >0). Calprotectin levels significantly correlated with symptom scores in UC (r = 0.561, P < 0.001), but not in CD. Fecal calprotectin levels correlate significantly with endoscopic disease activity in IBD. The test appears useful in clinical practice for assessment of endoscopic activity and remission.

P111 “EARS” (Erlanger Activity Related Score) of IBD: A new tool that allows accurate in vivo assessment of inflammatory activity in ulcerative colitis

Background: Increased vascular permeability and angiogenesis play a crucial role in the pathogenesis of inflammatory bowel disease (IBD). Previously, magnifying endoscopy and chromoendoscopy have been shown to be reliable tools for predicting histological assessment of severity in patients with mild or even inactive disease. i-scan (Pentax, Tokyo, Japan) was recently introduced as a novel computed virtual chromoendoscopy technique which enables a clear visualization of the mucosal vascular pattern within the gastrointestinal tract. Aim was to determine whether i-scan has the potential to enhance assessment of disease severity and extent in patients with mild or inactive IBD in comparison to high-definition white light endoscopy (HD-WL). Methods: Consecutive patients with IBD were randomly assigned at a 1:1 ratio to undergo colonoscopy with HD-WL (Group 1) or i-scan (Group 2). The mucosal vascular pattern and any mucosal abnormalities were recorded. Inflammation in ulcerative colitis was recorded according to Mayo ulcerative endoscopic score and in Crohn’s disease according to Crohn’s Disease Endoscopic Index of Severity (CDEIS). Subsequent to endoscopic characterization targeted biopsies were obtained from every segment for subsequent histopathological analysis of disease activity. Results: Overall, 100 patients were screened to participate in this study of whom 78 patients (HD white light, n = 39; i-scan, n = 39) completed the study protocol thereby matching the previously calculated sample size. Average duration of the examination was 18 minutes in group A and 20.5 minutes in group B which was not statistically significant. When comparing the endoscopic prediction of inflammatory extent and activity with the histological results an overall agreement of 51.28% and 56.41% (group A) and 92.31% and 89.74% (group B) was found, respectively. These differences were statistically significant (p = 0.0009 and p = 0.011). Conclusions: The present study indicates that i-scan significantly improves the diagnosis of the severity and extent of mucosal inflammation in patients with IBD. This newly developed imaging technique will therefore have important implications for diagnostic and therapeutic interventions in patients with IBD.

Crohn’s disease activity: quantitative contrast-enhanced ultrasound assessment

To determine whether quantitative parameters from contrast-enhanced ultrasound examination (CE-US) of the bowel wall correlate with endoscopic inflammatory activity in Crohn's disease and to assess its utility in the follow-up of patients on treatment. This was a prospective study of 30 patients with Crohn's disease requiring colonoscopy or flexible sigmoidoscopy. The Crohn's disease activity index (CDAI), serum C-reactive protein (CRP) and Crohn's disease endoscopic index of severity (CDEIS) were calculated. CE-US was performed within 7 days of endoscopy using intravenous perflutren lipid microsphere and repeated a median of 45.5 days following treatment. Time-intensity curves of bowel wall enhancement were generated to derive the area under the curve (AUC), time to peak intensity (TTP) and peak intensity (PI). In separate multivariate regression models, the AUC, TTP and PI showed no significant association with endoscopic activity whilst controlling for CDAI and CRP. However, the reductions in CDAI and CRP following treatment were mirrored by significant reductions in TTP (P = 0.05). CE-US does not appear to predict for Crohn's disease endoscopic activity independent of simple parameters such as CDAI and CRP. However, it may be useful in the serial assessment of patients on treatment.

Magnetic resonance imaging for evaluation of Crohnʼs disease

The use of magnetic resonance imaging (MRI) for assessment of Crohn's disease (CD) is expanding. The aim of this study is to define and provide an external validation of the MRI predictors of active CD, severe CD, and a quantitative Magnetic Resonance Index of Activity (MaRIA). In all, 48 patients with clinically active (n = 29) or inactive (n = 19) CD underwent ileocolonoscopy (reference standard) and MRI. T2-weighted and pre- and postcontrast-enhanced T1-weighted sequences were acquired. Endoscopic activity was evaluated by the Crohn's Disease Endoscopic Index of Severity (CDEIS), and also classified as absent, mild (inflammation without ulcers), or severe (presence of ulceration). In complete agreement with a previous derivation study, independent predictors of disease severity using CDEIS as a reference were wall thickness, relative contrast enhancement (RCE), presence of edema, and ulcers on MRI. Estimation of activity in each segment using this regression model, or another with simplified coefficients (MaRIA(S) = 1.5*wall thickness + 0.02*RCE + 5*edema + 10*ulceration) correlated with CDEIS (r = 0.798, P< 0.001; r = 0.80 P < 0.001, respectively). In the validation cohort both indexes had a high and equal accuracy for diagnosis of active disease: receiver operator characteristic (ROC) area 0.93, sensitivity 0.87, specificity 0.87 using a cutoff point ≥ 7, and for diagnosis of severe disease: ROC area 0.96, sensitivity 0.92, specificity 0.92 using a cutoff point ≥ 11. The total of segment values (MaRIA(T)) correlated with global CDEIS (r = 0.83, P< 0.001). The MRI variables that should be evaluated in clinical practice to diagnose active CD and severe CD are validated, as well as the quantitative index of activity for use in research studies.

Health-Related Quality of Life Improvements in Patients with Active Crohnʼs Disease Following Treatment with Certolizumab Pegol in the MUSIC Study (NCT00297648)

Purpose: To assess change in health-related quality of life (HRQoL) in patients with Crohn's disease (CD) treated with certolizumab pegol (CZP) in the MUSIC study. Methods: Patients in the MUSIC study had active CD (CD Activity Index score >225 to <450) and were treated with open-label CZP (400 mg subcutaneously [sc] every 2 weeks for 3 doses, then 400 mg sc every 4 weeks) for up to 54 weeks. Patients completed the Inflammatory Bowel Disease Questionnaire (IBDQ) at baseline, Week 10, and Week 54 to assess HRQoL. The IBDQ includes 32 questions that examine 4 aspects of patients' lives: bowel symptoms, systemic symptoms, emotional function, and social function (range of total score, 32-224). Least squares (LS) mean change (SD) in IBDQ total scores from baseline to Week 10 and Week 54 were evaluated; categorical rates of response (increase in IBDQ total score of ≥16 points) and remission (IBDQ total score ≥170 points) at each time point were also assessed. An exploratory analysis of the correlation between HRQoL remission as measured by the IBDQ and endoscopic remission as measured by the CD Endoscopic Index of Severity (remission, <6 points) was also performed. Results: A total of 89 patients entered the study; the IBDQ was completed by 78 patients at Week 10 and by 50 patients at Week 54. At baseline, mean (SD) IBDQ total score was 120.2 (29.8). At Week 10, LS mean (SD) change in IBDQ total score was 43.8 (33.8), the response rate was 66.3% (95% CI for percentage response, 55.5-76.0%), and the remission rate was 43.8% (95% CI, 33.3-54.7%). At Week 54, LS mean (SD) change in IBDQ total score was 44.1 (32.8), the response rate was 43.8% (95% CI, 33.3-54.7%), and the remission rate was 29.2% (95% CI, 20.1-39.8%). In the intent-to-treat population with an available endoscopic assessment at Week 10, the overall IBDQ remission rate was 69.7% in patients with endoscopic remission compared with 33.3% in patients not reaching endoscopic remission. Similar results were observed at Week 54. Conclusion: In patients with active CD, treatment with CZP at recommended dosages resulted in substantial improvement in HRQoL at both 10 and 54 weeks of therapy as measured by the IBDQ. Higher rates of IBDQ remission were associated with endoscopic remission compared with nonremission. Further evaluation of the impact of CZP therapy on improvement in HRQoL is warranted. Disclosure: Ernault - Employee UCB Coteur - Employee of UCB Colombel - Consultant, Lecturer, Grant and Research Support from UCB Lemann - Consultant for UCB Hebuterne - Consultant for UCB. This research was supported by an industry grant from UCB.

Infliximab and Azathioprine for Crohn's Disease: A Super-Sonic Combination?

Infliximab and Azathioprine for Crohn's Disease: A Super-Sonic Combination?

Serum immune-activation potency and response to anti-TNF-α therapy in Crohn's disease

To study whether immune-activation stage in serum of adult Crohn's disease (CD) patients correlates with disease activity and with treatment response to anti-tumor necrosis factor-α (TNF-α) therapy. Serum samples were obtained from 15 adult CD patients introduced to anti-TNF-α therapy. The individual stage of immune activation was studied applying our new in vitro assay, in which target cells (donor derived peripheral blood mononuclear cells) were cultured with patient serum and the T-cell activation induced by the patient serum was studied using a panel of markers for effector [interferon γ (IFNγ), interleukin (IL)-5] and regulatory T-cells [forkhead transcription factor 3 (FOXP3) and glucocorticoid-induced tumour necrosis factor receptor (GITR)]. The endoscopic disease activity was assessed with the Crohn's disease endoscopic index of severity (CDEIS) before and 3 mo after therapy with an anti-TNF-α agent. Low induction of FOXP3 and GITR in target cells cultured in the presence of patient serum was associated with high disease activity i.e. CDEIS assessed before therapy (r = -0.621, P = 0.013 and r = -0.625, P = 0.013, respectively). FOXP3 expression correlated inversely with pre-treatment erythrocyte sedimentation rate (r = -0.548, P = 0.034). Low serum induced FOXP3 (r = -0.600, P = 0.018) and GITR (r = -0.589, P = 0.021) expression and low IFNγ secretion from target cells (r = -0.538, P = 0.039) associated with treatment response detected as a decrease in CDEIS. The immune-activation potency in the patient serum prior to anti-TNF-α therapy reflected intestinal inflammation and the therapeutic response.

Circulating Cytokines Reflect Mucosal Inflammatory Status in Patients with Crohn’s Disease

There is a great need for a simple activity assessment tool that can reliably predict activity in patients with Crohn's disease (CD). To investigate the relationship between serum cytokines and endoscopic activity of CD using Crohn's Disease Endoscopic Index of Severity (CDEIS) as a gold standard. We prospectively evaluated 32 firmly established CD patients using ileocolonoscopy, CDEIS score, and Crohn's Disease Activity Index (CDAI) score. Blood samples for cytokine analysis were obtained 1 day prior to procedure. The correlation between CDEIS and CDAI was moderate (r = 0.43; P = 0.01); however, the correlation between CDEIS and inflammatory cytokines was excellent, with the highest coefficients for tumor necrosis factor alpha (TNFalpha) and interleukin-6 (IL-6) (r = 0.96 and r = 0.96, respectively; P < 0.001). CDEIS and anti-inflammatory cytokines were correlated nonlinearly (power function). We identified two separate models for predicting CDEIS value, based on the best performing pro-inflammatory [CDEIS = 0.445 x (IL-6) - 5,143] and anti-inflammatory [CDEIS = 27.478 x (IL-10)(-0.71)] cytokines. Both IL-6 and IL-10 models had high adjusted R(2) values (0.916 and 0.954, respectively). IL-6 had excellent diagnostic accuracy for detecting patients with CDEIS >7 (active disease), with area under the receiver operating characteristic (ROC) curve of 1.0 [95% confidence interval (CI) = 0.89-1.0; P < 0.001]. Serum cytokine levels are excellent predictors of endoscopic activity in patients with CD.

Changes in matrix metalloproteinase (MMP) and tissue inhibitors of metalloproteinases (TIMP) expression profile in Crohn's disease after immunosuppressive treatment correlate with histological score and calprotectin values

Matrix metalloproteinases (MMPs) constitute a family of enzymes capable of degrading various extracellular matrices (ECM) and basement membrane components playing a role in ECM turnover. They activate and degrade signaling molecules, such as cytokines and chemokines. MMPs are involved in inflammation and have been implicated in tissue degradation and repair occurring in inflammatory bowel disease. The aim of this study was to investigate the MMP profile of intestinal Crohn's disease (CD) patients before and after immunosuppressive treatment (anti-TNF-alpha agents or corticosteroids and conventional immunosuppressants azathioprine or methotrexate) to learn more about the therapeutic pathways for immunosuppressive agents. Expression of MMP-1, MMP-7, MMP-9, MMP-10, and MMP-26 and tissue inhibitors of metalloproteinases (TIMP)-1 and TIMP-3 was studied by immunohistochemistry in pretreatment and post-treatment tissue samples. Semiquantitative immunohistochemical scores were tested for correlations with fecal and serum inflammation markers as well as endoscopic and clinical disease activity scores. Neutrophil MMP-9 (p = 0.039) and MMP-26 (p = 0.030) and stromal TIMP-1 (p = 0.041) and TIMP-3 (p = 0.029) decreased along with treatment. However, expression of TIMP-3 by enterocytes tended to increase. Total histological score demonstrated positive correlation with neutrophil MMP-9 (p = 0.000), MMP-26 (p = 0.014), and macrophage TIMP-1 (p = 0.001). Calprotectin followed a similar pattern with stromal MMP-26 (p = 0.011), TIMP-1 (p = 0.000), and TIMP-3 (p = 0.001). Crohn's disease endoscopic index of severity (CDEIS) value correlated positively with macrophage TIMP-1 (p = 0.007) and stromal TIMP-3 (p = 0.005). Epithelial TIMP-3 presented with negative correlations with CDEIS (p = 0.006) and C-reactive protein values (p = 0.004). Our results suggest that immunosuppressive drugs modulate disease activity in CD by downregulation of MMP-9 and MMP-26 positive neutrophils and stromal TIMP-1 and TIMP-3.

Mapping of T1‐values and Gadolinium‐concentrations in MRI as indicator of disease activity in luminal Crohn's disease: A feasibility study

To determine the feasibility of T1-mapping and calculation of Gadolinium-values in luminal Crohn's Disease (CD). Nine patients with active CD were included. For each patient disease activity was determined, based on endoscopic and histopathological results. The Crohn's Disease Endoscopic Index of Severity (CDEIS), the Harvey-Bradshaw index (HBI) and C-reactive protein (CRP) were also determined as reference standards. T1-measurements were performed before and after intravenous administration of Gadodiamide in 14 slices in a single breath-hold using the Look-Locker (LL) sequence in combination with a segmented three-dimensional Turbo Field Echo sequence. A Region of Interest (ROI) was drawn around inflamed bowel loops and the mean Gadolinium-concentration within the ROI was calculated. Gadolinium-concentrations were compared between patients with mild and marked disease, as determined by the reference standards. Mean Gadolinium-concentrations were higher in bowel loops of patients with more active disease, as defined by endoscopic and histopathological examination, CRP, and HBI. By using a breath-hold LL sequence in the bowel quantitative assessment of contrast agent concentration is possible, thus permitting objective evaluation of physiological changes in actively inflamed tissue in an area that suffers from motion problems.

Magnetic resonance for assessment of disease activity and severity in ileocolonic Crohn’s disease

Objective:Assessment of disease extension and activity is crucial to guide treatment in Crohn’s disease. The objective of the current cross-sectional study was to determine the accuracy of MR for this...

Inflammatory bowel disease activity assessed by fecal calprotectin and lactoferrin: correlation with laboratory parameters, clinical, endoscopic and histological indexes

BackgroundResearch has shown that fecal biomarkers are useful to assess the activity of inflammatory bowel disease (IBD). The aim of the study is: to evaluate the efficacy of the fecal lactoferrin and calprotectin as indicators of inflammatory activity.FindingsA total of 78 patients presenting inflammatory bowel disease were evaluated. Blood tests, the Crohn's Disease Activity Index (CDAI), Mayo Disease Activity Index (MDAI), and Crohn's Disease Endoscopic Index of Severity (CDEIS) were used for the clinical and endoscopic evaluation. Two tests were performed on the fecal samples, to check the levels of calprotectin and lactoferrin. The performance of these fecal markers for detection of inflammation with reference to endoscopic and histological inflammatory activity was assessed and calculated sensitivity, specificity, accuracy.A total of 52 patient's samples whose histological evaluations showed inflammation, 49 were lactoferrin-positive, and 40 were calprotectin-positive (p = 0.000). Lactoferrin and calprotectin findings correlated with C-reactive protein in both the CD and UC groups (p = 0.006; p = 0.000), with CDAI values (p = 0.043; 0.010), CDEIS values in DC cases (p = 0,000; 0.000), and with MDAI values in UC cases (p = 0.000).ConclusionFecal lactoferrin and calprotectin are highly sensitive and specific markers for detecting intestinal inflammation. Levels of fecal calprotectin have a proportional correlation to the degree of inflammation of the intestinal mucosa.