Activity Score For Crohn's Disease Research Articles

Development and validation of a novel therapeutic drug monitoring-based nomogram for prediction of primary endoscopic response to anti-TNF therapy in active Crohn's disease.

Anti-tumor necrosis factor (TNF) monoclonal antibodies, especially infliximab (IFX) and adalimumab (ADA), are considered the first-line treatment for active Crohn's disease (CD). However, the predictive role of therapeutic drug monitoring (TDM) of serum anti-TNF in monitoring the treatment of inflammatory bowel disease (IBD) remains controversial. To explore the correlation between serum anti-TNF levels and early endoscopic response in active CD using a TDM-based nomogram. Cross-sectional study. The simplified endoscopic activity score for CD (SES-CD), Crohn's disease activity index (CDAI), laboratory parameters, and the serum trough levels of IFX and ADA were assessed. The trough levels of IFX or ADA were significantly higher in patients with endoscopic response compared to non-responders in the development cohort (p < 0.001). The IFX and ADA levels showed a weak but significantly negative correlation with SES-CD (p < 0.001), CDAI (p < 0.001), and C-reactive protein (CRP) (p < 0.001) at week 14 post-IFX therapy in the development cohort. Furthermore, the receiver operating characteristic curve revealed that an optimal level of IFX (4.80 μg/mL) and ADA (8.80 μg/mL) exhibited the best performance in predicting endoscopic response. Concomitantly, we developed a novel nomogram prediction model based on the results of multivariate logistic regression analysis, which consisted of CRP, albumin (Alb), and anti-TNF trough levels at week 14. The nomogram showed significant discrimination and calibration for both IFX and ADA in the development cohort and performed well in the external validation cohort. This study demonstrates a robust association between serum concentrations of IFX, ADA, Alb, and CRP and primary endoscopic response in active CD patients. Importantly, the TDM- and laboratory marker-based nomogram may be used to evaluate the primary endoscopic response to anti-TNF therapy, especially for optimizing treatment strategies and switching therapy in CD patients.

Association of Periodontal Disease with Activity of Crohn's Disease.

Crohn's disease (CD) is a chronic inflammatory granulomatous disease that can affect the entire gastrointestinal tract. It is characterized by various extraintestinal manifestations (EIMs), of which oral manifestations (OMs) are often possible. One of the possible OMs is periodontal disease (PD), a chronic inflammatory condition of the supporting tissues of the teeth. This study aimed to show the existence of a mutual relationship between the clinical activity of PD and the clinical and endoscopic activity of CD. One clinical and two endoscopic indexes were used for the assessment of CD activity and clinical attachment loss (CAL), bleeding on probing (BOP), pocket probing depth (PPD), and radiographic bone loss (RBL) in a dental panoramic tomogram to assess PD in CD patients. A total of 38 patients underwent the entire study process, of which 20 patients had CD and 18 patients had CD and PD. Considering all CD activity scores, there were 26 patients with active disease; half of them had PD, and 85.7% of operated patients had active CD. The values of CAL, PPD, BOP, and RBL were higher in active CD patients than those in remission, except for BOP when comparing to the CDAI score, which was higher in those in remission of CD. The results of this study indicate that there is a connection between the activity of CD and worse conditions of the supporting tissues of the gums in the oral cavity, so it is important to keep in mind the necessity of referring patients with CD to a dentist for timely and adequate therapeutic measures.

Correlation between Treatment Outcomes and Serum Vitamin D Levels As Well As Infliximab Trough Concentration among Chinese Patients with Crohn's Disease.

The relationship between vitamin D (vit-D) levels and the effectiveness of infliximab (IFX) in patients with Crohn's disease (CD) remains controversial. To evaluate the interaction between vit-D levels and the response to IFX therapy in patients with CD. This was a retrospective cohort study. Serum vit-D and IFX trough concentrations (TC) were measured in 84 patients, and statistical analyses were performed. The total vit-D deficiency rate at enrollment, at week 14 and week 38, was 64.3%, 41.67%, and 37.5%, respectively (P < 0.001). CD activity index (CDAI) (120, range, 93-142.75) and simplified endoscopic activity score for CD (SES-CD) (2, range, 0-4) at week 14 were lower than that of enrollment (CDAI, 136.5, range, 101.25-196; SES-CD 13, range, 5-23) (P < 0.001). The biochemical remission (BR), clinical remission (CR), endoscopic remission (ER), and response (ERe) rates of week 38 were 76.1%, 88.5%, 22.4%, and 67.2%, respectively. vit-D levels at enrollment were positively correlated with CDAI at week 38 (P = 0.024). IFX serum TC was related to BR (P = 0.036), CR (P = 0.032) at week 14, and ERe (P = 0.009) at week 38. Among Chinese patients with CD, vit-D levels prior to IFX therapy are related to CDAI scores, and IFX serum TC is associated with BR, CR, and ERe.

The use of therapeutic drug monitoring for early identification of vedolizumab response in Saudi Arabian patients with inflammatory bowel disease

Vedolizumab is a humanized monoclonal antibody used to treat moderate-to-severe inflammatory bowel disease (IBD). The aim of the study was to assess the effectiveness of the induction of vedolizumab trough level in predicting short-term (week 14) clinical outcomes, and covariates that affect the response in Saudi Arabian patients. This prospective, real-life study included a total of 16 patients (4 Crohn's disease (CD) and 12 ulcerative colitis (UC)) with a confirmed diagnosis of IBD and generally naïve to receiving vedolizumab therapy. Using ELISA assay, vedolizumab induction trough and peak levels were measured at weeks 0, 2, and 6. The follow-up assessment was at week 14, where clinical outcomes were measured using the partial Mayo score for UC, and the CD activity score (CDAI), and Harvey Bradshaw index (HBI) for CD. At week 14, 9 patients (52.9%) out of 16 patients demonstrated response to therapy; clinical remission was reported in 5 patients (29.4%), and in 4 cases a clinical response was noted (23.5%). Clinical remission at week 14 was linked significantly with week 6 median vedolizumab levels in responders (25.1 µg/ml 95% CI: 16.5–42.9) compared to non-responders (7.7 µg/ml, 95% CI: 4.6–10.6) (P = 0.002). Receiver operator curve analysis at week 6 identified a cut-off > 8.00 µg/mL for short-term clinical remission. Also, at week 14, BMI significantly correlated with week 6 vedolizumab trough levels (P = 0.02). No other covariates correlated with drug levels at any time point examined. Week 6 early vedolizumab trough level measurements in IBD patients predicted short-term week 14 clinical remission.

Alteration of the Inflammatory and Anti-Inflammatory Cytokine Profiles of Peripheral Blood Mononuclear Cell in Crohn's Disease Patients after Following up.

Background:Crohn’s disease (CD) has a chronic course, which its recurrence varies widely among different patients. In this study we prospectively analyzed blood samples of 19 CD patients. Alteration in transcription of inflammatory and anti-inflammatory cytokines was analyzed compared with household members after three month follow up.Methods:CD patients were diagnosed based on clinical symptoms, endoscopic and histopathologic characteristics. Nineteen CD patients and their households were evaluated from Jun 2019 to Feb 2021 at Tehran university hospitals. CD activity score, biological, clinical and demographic data of the patients were recorded at two time point intervals. Bacteriological tests were done using aerobic and anaerobic blood cultures. To investigate transcriptional alterations, peripheral blood mononuclear cells (PBMCs) were isolated using Ficol centrifugation method and relative quantitative real-time PCR was done to determine the expression level of IFN-γ, TNF-α, IL10, and FOXP3 cytokines.Results:Our results showed a correlation between fecal calprotectin level (709.8 ± 554.6), C-reactive protein concentration (18.1 ± 15.9), and erythrocyte sedimentation rate (30.4 ± 17.9) with disease activity (Flare/remission). IL10 and Foxp3 anti-inflammatory gene’s expression were significantly (P = 0.003 for IL10 and P = 0.008 Foxp3) higher during the flare and remission in patients with active disease respectively. Bacteriological examination showed infection with Streptococcus spp. and Clostridium spp. in two CD patients during flares, which was correlated with upregulation and down-regulation of IL10, TNF-α, IFN-γ and FOXP3 proteins, respectively.Conclusion:Occurrence of bacteremia, and higher amount of CAP, CRP and ESR are correlated with higher level of transcription for inflammatory cytokines, which could effectively reflect the disease activity. Raise in FoxP3 transcription proposed change in Treg sub-population in PBMC or its activity during the CD remission phase.

P186 Can transabdominal bowel ultrasound accurately detect both small and large bowel Crohn Disease in pediatric patients when compared to MRE?

Abstract Background Magnetic resonance enterography (MRE) has been the modality of choice to assess small bowel inflammation in patients with Crohn disease (CD). It can also assess large bowel when not feasible to assess endoscopically. Transabdominal bowel ultrasound (TABUS) is an attractive non-invasive tool to assess CD activity. Studies to date have focused on its correlation to large bowel endoscopic findings in adult CD. This study aimed to compare TABUS and MRE in identifying small and large bowel CD in pediatric patients. Methods Pediatric patients (≤18 years old) seen for suspected CD were prospectively enrolled and underwent baseline TABUS, endoscopy, MRE, blood work and stool studies. The Pediatric Crohn’s Disease Activity Index (PCDAI) and Simple Endoscopic Score for Crohn’s Disease (SES-CD) were used to assess disease activity. Bowel wall thickness (BWT) was assessed by TABUS and MRE. TABUS measurements were scored with the Simple Ultrasound Activity Score for Crohn Disease (SUS-CD) (0=≤3mm, 1=3–4.9mm, 2=5–7.9mm, 3=≥8mm). Pearson Chi-square was used to compare BWT between TABUS and MRE. Results 21 patients (71% male) were included, with a median age of 13 years (range 6–16). Median PCDAI was 40 (25–49) and SES-CD 15 (6.5–22). There was a high level of agreement between MRE and TABUS (Figure 1) with some disagreement in the jejunum (n=9/21, 43%). For terminal ileal (TI) disease where there was disagreement, endoscopy of TI was in agreement with TABUS in two patients and MRE in five patients. Endoscopic TI disease that was documented as normal on TABUS was mild (SES-CD 3). In patients with abnormal MRE, BWT was not significantly different between the two modalities (Table 1). In patients with normal MRE, TABUS SUS-CD scores were accurately 0 in almost all segments (score 1 in TI) (Table 2). TABUS correctly identified no fistulae and 2 small bowel strictures (identified at endoscopy), but did not detect 1 intra-abdominal abscess and 4 large bowel strictures (only 1 stricture seen on endoscopy). Excessive lymph nodes (&amp;gt;4) were successfully seen on TABUS in 10/16 patients. TABUS correctly identified 75% of patients with significant mesenteric fibrofatty proliferation. Hyperemia on TABUS corresponded to an abnormal MRE for that segment in 92–100% of small bowel and 50–86% of large bowel. Conclusion TABUS and MRE are comparable modalities in the assessment of small and large bowel disease in newly diagnosed pediatric CD patients. Assessment of proximal small bowel is complex, and MRE may over-call disease. MRE still plays an important role in assessing abscesses and mild large bowel narrowing. Hyperemia on TABUS is an important indicator of active bowel inflammation, and is particularly useful for endoscopically inaccessible small bowel.

Magnetic resonance imaging-based body composition is associated with nutritional and inflammatory status: a longitudinal study in patients with Crohn's disease

ObjectiveTo evaluate the changes in magnetic resonance imaging-based body composition parameters during follow-ups in patients with Crohn's disease (CD).MethodsBetween November 1, 2017, and June 30, 2021, patients diagnosed with CD, who underwent two or more magnetic resonance enterography (MRE) scans at our institution were retrospectively reviewed. The baseline and one subsequent follow-up scan for each patient were paired to form longitudinal comparisons. Skeletal muscle, visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) indexes were calculated from tissue areas measured at the third lumbar vertebra level per scan, standardized by dividing the height2 and lumbar height2 (heightL1–L5). We also assessed the correlation between changes in VAT to total adipose tissue ratio (VA/TA index) and CD activity scores (5-point MRE classification) using Spearman’s correlation analysis. A multivariate linear regression model was used to adjust for the follow-up duration and treatment type.ResultsOverall, 49 patients (with 49 paired scans) were enrolled. VA/TA index changes were negatively correlated with changes in skeletal muscle index (SMI; r = − 0.339, p < 0.05). The VA/TA index (52.69 ± 10.66% vs. 49.18 ± 10.80%, p < 0.001) and the total MRE score (8.0 ± 3.9 vs. 5.7 ± 3.4, p < 0.001) decreased significantly during follow-up, regardless of follow-up duration and treatment type (both p > 0.05). Changes in total MRE score were negatively correlated with SMI changes (r = − 0.408, p < 0.01) but positively correlated with VA/TA index changes (r = 0.479, p < 0.01).ConclusionAn increase in SMI and a decrease in VA/TA index could reflect improved nutritional and inflammatory status.

Predictive Value of Bowel Ultrasound in Crohn’s Disease: A 12-Month Prospective Study

Mucosal healing is associated with better outcomes in Crohn's disease (CD). Colonoscopy is invasive and poorly tolerated. Bowel ultrasound (US) is a noninvasive tool that increasingly is being used for CD assessment. We assessed the predictive role of baseline bowel US findings on disease course in a large prospective cohort of CD patients for 12 months. Ileocolonic CD consecutive patients were followed up for 12 months after performing bowel US. The negative course of CD, defined as the need for steroids and/or change of therapy and/or hospitalization and/or the need for surgery, was assessed. We evaluated this composite end point and subsequently considered each individual end point separately. Predictors of negative disease course were analyzed by logistic regression analysis. There were 225 ileal and/or colonic CD consecutive patients included in the study. We analyzed the association between baseline bowel US parameters and endoscopic activity (defined as a Simplified Endoscopic Activity score for CD > 2) to set up a noninvasive quantitative ultrasound-based score (bowel ultrasound score). The multivariable analysis identified the following independent predictors of a worse outcome throughout the 12-month period as follows: bowel ultrasound score greater than 3.52 (odds ratio [OR], 6.97; 95% CI, 2.87-16.93; P < .001), presence of at least 1 disease complication (stricture, fistula, abscess) at baseline bowel US (OR, 3.90; 95% CI, 1.21-12.53; P= .021), fecal calprotectin value of 250 μg/g or greater at baseline (OR, 5.43; 95% CI, 2.25-13.11; P < .001), and male sex (OR, 2.60; 95% CI, 1.12-6.02; P= .025). Bowel US predicts the 12-month course in CD.

Assessment of Ileocolonic Inflammation in Crohn's Disease: Which Surrogate Marker Is Better-MaRIA, Clermont, or PET/MR Index? Initial Results of a Feasibility Trial.

Our objective was to define an 18F-FDG PET/MR enterography index as a hybrid surrogate marker for active ileocolonic inflammation in Crohn's disease (CD) and assess its diagnostic performance in comparison to validated MR indices (MR index of activity [MaRIA], Clermont score). Methods: Fifty-two CD patients with recurrent symptoms underwent ileocolonoscopy and 18F-FDG PET/MR enterography. Three hundred three ileocolonic segments were assessed for inflammation using MaRIA and the Clermont score as well as the newly defined PET/MR index. On the basis of tobit regression, the PET/MR index was defined as (0.87 × wall thickness) + (1.97 × edema) + (0.83 × ulceration) + (0.55 × SUVmax ratio) + 1.14. The endoscopic activity of inflammation was determined by the simplified endoscopic activity score for CD (SES-CD). Receiver-operating-characteristic curves for each surrogate marker were created and tested against each other using the DeLong test, and diagnostic accuracies were compared using the McNemar test. Correlations between surrogate markers and SES-CD were tested with the Spearman rank correlation test. Results: The PET/MR index showed a comparable sensitivity but a significantly higher specificity and accuracy than MaRIA and the Clermont score in predicting both active and severe inflammation (active inflammation: specificities of 0.933, 0.711, and 0.707 and accuracies of 0.921, 0.739, and 0.736, P < 0.001; severe inflammation: specificities of 0.91, 0.81, and 0.785 and accuracies of 0.914, 0.818, and 0.795, P < 0.01, respectively). All surrogate markers correlated moderately with SES-CD on a segmental basis and a global level (0.5 < ρ < 0.7, all P < 0.001). Conclusion: As a hybrid surrogate marker comprising MR parameters and the PET component, the PET/MR index yielded significantly improved specificity and diagnostic accuracy compared with conventional MR indices (MaRIA and the Clermont score), demonstrating its high potential for noninvasive assessment of CD.

Quantitative study on grading activity of Crohn disease with CT enterography

Objective To explore the feasibility and the value of CT enterography (CTE) in the quantitative evaluation of Crohn's disease (CD). Methods Retrospectively analyzed 49 patients diagnosed as CD by clinical, enteroscopy, pathology, and imaging from April 2016 to June 2017 in Zhongnan Hospital of Wuhan University. All patients underwent routine enteroscopy and standardized CTE. The interval between the two examinations was less than 2 weeks. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were measured at intervals. The ESR ranged from 2.0 to 97.0 mm/1 h, with an average of (30.6±26.5) mm/1 h, CRP from 0.3 to 143.3 mg/L, and a median of 27.7 mg/L. CD patients were classified into inactive, mild and moderate-severe according to Crohn's disease simplified endoscopic activity score(SES-CD) after enteroscopy. CTE evaluated the site of lesion, the thickness and enhanced patterns of the most severe lesions of the bowel wall, mural enhanced CT value in the portal vein phase, ΔCT value, stenosis, perienteric inflammation, mesenteric hypervascularity (comb sign), enlarged lymph nodes, abdominal abscesses, fistulas, etc. The Chi-square test was used to compare the differences of enhanced patterns among different groups. ANOVA (Analysis of Variance) was used to compare the differences in bowel wall thickness, plain CT values, mural enhanced CT value in the portal vein phase and ΔCT values among different groups. The correlation between CTE parameters and SES-CD or laboratory data was analyzed by Pearson (normal distribution data) or Spearman (skewed distribution data). Results SES-CD ranged from 1 to 15, with an average of 5.1±2.6. Among 49 cases, 13 were inactive, 19 were mild, and 17 were moderate-severe. There were 25 cases of intestinal obstruction or stenosis, including 24 cases in the active group and 1 case in the non-active group, and the difference was statistically significant (χ2=13.3, P 0.05). Bowel wall thickness, mural enhanced CT value in the portal vein phase and ΔCT values were all moderately correlated with SES-CD (r were 0.564, 0.585, 0.533, respectively; P all 0.05). Conclusion The bowel wall thickness, mural enhanced CT value in the portal vein phase and the ΔCT value can be used to accurately assess the activity of CD lesions. Key words: Crohn disease; Tomography,X-ray computed; Simplified endoscopic activity score for Crohn disease

Efficacy of vedolizumab for induction of clinical response and remission in patients with moderate to severe inflammatory bowel disease who failed at least two TNF antagonists.

Vedolizumab is a recently available monoclonal antibody targeting α4β7 integrin for the treatment of ulcerative colitis (UC) and Crohn's disease (CD). The objective of this article is to evaluate the efficacy of vedolizumab induction therapy in anti-TNF-refractory/intolerant UC and CD patients in real life. A cohort of 149 moderately to severely active UC and CD patients who failed or showed intolerance to at least two TNF antagonists participated in a medical need program and received vedolizumab in 37 Belgian centers (April-September 2015). Rates of clinical response and remission were retrospectively evaluated at Week 10 for UC and Week 14 for CD using the physician's global assessment (PGA), Mayo score and Harvey Bradshaw index (HBI) or Crohn's disease activity score (CDAI) scores. Eighty-four patients (29 UC, 55 CD) had sufficient data for analysis. For UC patients, clinical response was observed in 76% based on PGA and 59% based on the Mayo score. The corresponding percentages for CD patients were 80% for PGA and 65% for HBI/CDAI. Clinical remission rates were 10% and 40% for UC and CD, respectively. Steroid-free remission was observed in respectively 10% and 35%. Globally, corticosteroids were stopped in 14 out of 48 patients (29%). No new safety signals were reported. Up to 70% TNF-refractory/intolerant UC and CD patients achieved a clinical response after 10 to 14 weeks of vedolizumab treatment in this real-life cohort.

P250 Correlation of faecal calprotectin levels with Crohn's disease activity scores using two different immunoassays

operative data for the extent of disease in 35 patients (77%) and in 37 patients (82%) for stenosis. Regarding any fistula presence and their tracks, imaging data and per-operative observations gave similar results for 62% of cases. Cross sectional imaging had overestimated fistula in 12 patients, had not found peroperatively described fistula in 3 patients and had incorrectly described the fistula tracks in 3 patients. Conclusions: In this study, cross sectional imaging data were not consistent with per-operative data in 53.33% of the cases. This discrepancy concerned mainly the fistula tracks description and the exact extent of disease.

FDG PET/CT in Crohn’s disease: correlation of quantitative FDG PET/CT parameters with clinical and endoscopic surrogate markers of disease activity

The aim of this study was to determine the feasibility and potential clinical utility of assessment of Crohn's disease (CD) activity by (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT employing a new quantitative approach. A total of 22 subjects (mean age 37) with CD who had undergone FDG PET/CT followed by ileocolonoscopy within 1 week were included in this analysis. The CD endoscopy index of severity (CDEIS) for various bowel segments was calculated. The CD activity index (CDAI) was evaluated, and fecal calprotectin was measured. On PET, regions with increased FDG uptake in large bowel were segmented with an adaptive contrast-oriented thresholding algorithm, and metabolically active volume (MAV), uncorrected mean standardized uptake value (SUV(mean)), partial volume-corrected SUV(mean) (PVC-SUV(mean)), SUV(max), uncorrected total lesion glycolysis (TLG = MAV × SUV(mean)), and PVC total lesion glycolysis (PVC-TLG = MAV × PVC-SUV(mean)) were measured. Global CD activity score (GCDAS) was calculated as the sum of PVC-TLG over all clinically significant FDG-avid regions in each subject. Correlations between regional PET quantification measures (SUVs, TLGs) and CDEIS were calculated. Correlations between the global PET quantification measure (GCDAS, global SUVs) with CDAI, fecal calprotectin, CDEIS, and CRP level were also calculated. SUV(max), PVC-SUV(mean), and PVC-TLG significantly correlated with segment CDEIS subscores (r = 0.50, r = 0.69, and r = 0.31, respectively; p < 0.05). GCDAS significantly correlated with CDAI and fecal calprotectin (r = 0.64 and r = 0.51, respectively; p < 0.05). By employing this new quantitative approach, we were able to calculate indices of regional and global CD activity, which correlated well with both clinical and pathological disease activity surrogate markers. This approach may be of clinical importance in measuring both global disease activity and treatment response in patients with CD.

Correlations of Plasma Citrulline Levels With Clinical and Endoscopic Score and Blood Markers According to Small Bowel Involvement in Pediatric Crohn Disease

Several studies have indicated that plasma citrulline levels reflect the extent of mucosal injury of the small intestine. This study was performed to determine whether plasma citrulline levels correlate with the disease activity in pediatric patients with Crohn disease (CD). A total of 63 CD and 23 ulcerative colitis (UC) patients were included in this study. Disease severity was assessed by pediatric CD activity index (PCDAI), pediatric UC activity index, simplified endoscopic activity score for CD, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). The correlations among these variables and plasma citrulline levels were evaluated. We performed subgroup analysis whether correlations between plasma citrulline levels and disease activity depend on small bowel involvement in patients with CD. The plasma citrulline levels correlated negatively with CRP (r = -0.332, P = 0.008), ESR (r = -0.290, P = 0.022), and PCDAI (r = -0.424, P = 0.001) in patients with CD. The plasma citrulline levels were significantly lower in patients with jejunal involvement than in those without (P = 0.027). In subgroup analysis, patients with CD with jejunal involvement showed significantly negative correlations of plasma citrulline levels with CRP (r = -0.628, P = 0.016) and PCDAI (r = -0.632, P = 0.015); however, patients with CD without jejunal involvement revealed no correlations of plasma citrulline levels with CRP and PCDAI. There were no significant correlations between plasma citrulline levels and simplified endoscopic activity score for CD. There were no significant correlations of plasma citrulline levels with CRP, ESR, and pediatric UC activity index in patients with UC. Plasma citrulline levels correlated with disease severity as measured by PCDAI, CRP, and ESR in pediatric patients with CD with jejunal involvement.

Evaluation of Crohn’s disease activity: Initial validation of a magnetic resonance enterography global score (MEGS) against faecal calprotectin

To develop an MRI enterography global score (MEGS) of Crohn's disease (CD) activity compared with a reference standard of faecal calprotectin (fC), C-reactive protein (CRP) and Harvey-Bradshaw index (HBI). Calprotectin, CRP and HBI were prospectively recorded for 71 patients (median age 33, male 35) with known/suspected CD undergoing MRI enterography. Two observers in consensus scored activity for nine bowel segments, grading mural thickness, T2 signal, mesenteric oedema, T1 enhancement and pattern, and haustral loss. Segmental scores were multiplied according to disease length. Five points each were added for lymphadenopathy, comb sign, fistulae and abscesses to derive the MEGS. A previously validated MRI CD activity score (CDAS) was also calculated. MRI scores were correlated with clinical references using Spearman's rank. A logistic regression diagnostic model was built to discriminate active (fC > 100 μg/g) from inactive disease. MEGS and CDAS were significantly correlated with fC (r = 0.46, P < 0.001) and (r = 0.39, P = 0.001) respectively. MEGS correlated with CRP (r = 0.39, P = 0.002). The model for discriminating active from inactive disease achieved an area under the receiver-operating curve of 0.75 and 0.66 after leave-one-out analysis. A magnetic resonance enterography global score (MEGS) of CD activity correlated significantly with fC levels. • Magnetic resonance imaging is now widely used to assess Crohn's disease. • Existing MRI activity scores depend on local segmental endoscopic/histological reference standards. • Scores including assessment of disease extent/complications better demonstrate full disease burden. • This new global Crohn's disease burden score correlates with calprotectin and CRP. • The MRI enterography score of disease activity can complement existing clinical markers.

Simple Enterographic Activity Score for Crohn’s Disease: comparison with endoscopic, biochemical, and clinical findings

Magnetic resonance enterography (MRE) is believed to be a reliable diagnostic method in assessing the activity of small-bowel Crohn's disease (CD). However, there are no scales for quantifying MRE scores that could be used in everyday clinical practice. The aim of the study was to construct a simple scale for assessing the activity of CD (Simple Enterographic Activity Score for Crohn's Disease - SEAS-CD) in MRE and to investigate its clinical usefulness. We conducted a retrospective analysis of MRE findings in 122 patients with CD. Disease activity was assessed using the SEAS-CD. The reference standard was endoscopic assessment using the Simple Endoscopic Score for Crohn's Disease (SES-CD). We assessed correlations between SEAS-CD and endoscopic, clinical, and biochemical findings. We also proposed the Global Crohn's Disease Activity Score to assess total CD activity by summarizing the colonic SES-CD and SEAS-CD scores. In the validation group (n = 62), a significant correlation between the ileal SES-CD and ileal SEAS-CD scores was noted (r = 0.72, P <0.0001). In patients with isolated small-bowel CD, there was a significant correlation between SEAS-CD and Crohn's Disease Activity Index (CDAI), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), hemoglobin (Hb), albumin, and platelet count. In patients with ileocolonic CD, the Global Crohn's Disease Activity Score correlated with CDAI, CRP, ESR, Hb, and hematocrit. SEAS-CD is a useful tool for the quantification of small-bowel CD activity assessed by MRE. The Global Crohn's Disease Activity Score may be useful in assessing the progression of lesions in patients with ileocolonic CD.

Dysmenorrhea in Women with Crohnʼs Disease

Dysmenorrhea and Crohn's disease (CD) have overlapping symptoms; however, their relationship is poorly understood. The aims of this study were to examine (1) the impact of dysmenorrhea on pain severity and pain medication use in CD and (2) the relationships between dysmenorrhea, CD activity, and health-related quality of life (HRQOL). This was a case-control study of menstruating women with and without CD. Subjects were assessed for dysmenorrhea, pain severity, medication use, menstrual distress, and HRQOL. CD activity scores were calculated. The correlation between menstrual distress and CD activity was assessed. Linear regression analysis was performed to determine the effects of dysmenorrhea and CD on pain severity. A total of 110 subjects were studied and 40% of cases had dysmenorrhea. Dysmenorrhea was associated with higher pain scores among cases. Compared with controls, cases with dysmenorrhea reported similar pain severity but lower nonsteroidal anti-inflammatory drug use. After adjusting for medication use, cases had significantly greater distress due to menstrual pain. CD activity scores were not higher in women with dysmenorrhea; however, menstrual distress scores correlated positively with disease activity. HRQOL was significantly lower in cases with dysmenorrhea by some measures. Dysmenorrhea is common in women with CD and has an additive effect on overall pain severity. It is not, however, associated with greater nonsteroidal anti-inflammatory drug use. Menstrual distress is positively correlated with CD activity scores and associated with lower HRQOL by some measures. Treatment of dysmenorrhea may improve the pain experienced by women with CD, the perception of CD activity, and the quality of life in women with CD.

Serial Changes of Cytokines in Crohn's Disease Treated with Infliximab

Infliximab (IFX) has been reported to be useful as induction therapy and/or maintenance therapy for Crohn's disease (CD). However, the effects of IFX on serial changes in cytokine levels have not been well characterized. We examined cytokine levels in CD patients before and after administration of IFX. A total of 37 patients with active CD were enrolled (24 men, 13 women; mean age, 31.9 years). Patients were given IFX 5mg/kg intravenously. Serum levels of 17 cytokines were simultaneously determined using a Bio-Plex suspension array system before treatment and, 4 and 8 weeks after IFX treatment. Patients were divided into two groups according to the disease duration: the 'early treatment' group and the 'in progress' treatment group. Serum IL-6, IL-7, IL-8 and MIP-1ß levels were significantly decreased in CD patients after IFX treatment compared to before treatment (p<0.05). In particular, serum levels of IL-8, IL-12 and MIP-1ß decreased significantly after IFX treatment in the 'in progress' treatment group. The changes in CD activity score (CDAI) after treatment were positively correlated with the changes of serum MIP-1ß. IFX treatment reduces serum levels of IL-6, IL-7, IL-8, IL-12 and MIP-1ß, which appears to be mediated by the inhibition of inflammation in CD.

Non-perforating small bowel Crohn's disease assessed by MRI enterography: Derivation and histopathological validation of an MR-based activity index

ObjectivesTo develop and validate a qualitative scoring system for enteric Crohn's disease activity using MR enterography (MRE). MethodsMRE was performed in 16 patients (mean age 33, 8 male) undergoing small bowel resection. Mural thickness, T2 signal, contrast enhancement, and perimural oedema were scored qualitatively (0–3) at 44 locations. Transmural histopathological scoring of acute inflammation (AIS) was performed at all locations (score 0–13). MRI parameters best predicting AIS were derived using multivariate analysis. The MRI activity index was applied to 26 Crohn's patients (mean age 32, range 13–69 years, 15 male) and correlated to terminal ileal biopsy scores of acute inflammation (“eAIS” score 1–6). Receiver operator characteristic curves were calculated. ResultsMural thickness (coefficient 1.34 (95% CI 0.36, 2.32)], p=0.007) and T2 signal (coefficient 0.90 (95% CI −0.24, 2.04) p=0.06) best predicted AIS (AIS=1.79+1.34*mural thickness+0.94*mural T2 score [R-squared 0.52]). There was a significant correlation between the MRI index and eAIS (Kendall's tau=0.40, 95% CI 0.11–0.64, p=0.02). The model achieved a sensitivity of 0.81 (95% CI 0.54–0.96), specificity of 0.70 (0.35–0.93) and AUC 0.77 for predicting acute inflammation (eAIS ≥2). ConclusionsA simple qualitative MRI Crohn's disease activity score appears predictive against a histopathological standard of reference.

Multiple doses of intravenous interleukin 10 in steroid-refractory Crohn's disease. Crohn's Disease Study Group

BACKGROUND & AIMS: Interleukin 10 (IL-10) is a cytokine with immunosuppressive and anti-inflammatory activities. Gene-targeted IL-10- deficient mice develop a chronic intestinal inflammatory disease that is reminiscent of Crohn's disease. The present double-blind randomized multicenter trial was designed to evaluate the safety, tolerance, and pharmacokinetics of IL-10 in Crohn's disease.METHODS: Forty-six patients with active steroid-resistant Crohn's disease were treated with one of five doses of recombinant human IL-10 (0.5, 1, 5, 10, or 25 micrograms/kg) or placebo administered once daily by intravenous bolus injection over 7 consecutive days.RESULTS: Treatment was safe and well tolerated, and no evidence for IL-10 accumulation was observed at the end of the treatment period. At the end of the study, Crohn's disease activity scores were 179 in IL-10-treated patients and 226 in patients receiving placebo. The proportion of patients that experienced a complete remission at any time in the 3-week follow-up period was 50% in the IL-10 group and 23% in placebo-treated patients.CONCLUSIONS: These results indicate that IL-10 administered as a daily bolus injection over 1 week is safe and well tolerated and may be clinically efficacious.(Gastroenterology 1997 Aug;113(2):383-9)