Simple Endoscopic Score For Crohn's Disease Research Articles

S754 Impact of Mirikizumab Treatment on Health-Related Quality of Life in Patients With Crohn’s Disease: A Phase 2 Study Analysis Using the SF-36

Introduction: This analysis evaluated Mirikizumab (miri) effects on Short Form Health Survey (SF-36) in the Phase (Ph)2 randomised, double-blind, parallel, placebo (PBO)-controlled study in patients (pts) with moderately-to-severely active Crohn’s disease (CD). Methods: 12-Week(W) Induction: 191 pts were randomized 2:1:1:2 to 4 treatment arms: intravenous (IV) PBO, 200, 600, or 1000mg miri every 4 weeks (Q4W; W0, 4, and 8). 40-W Maintenance: For miri induction dose, pts achieving ≥1-point improvement in Simple Endoscopic Score for CD (SES-CD) at W12 were re-randomized 1:1 to double-blind maintenance treatment from W12 to W48: continuation of induction IV treatment assignment (IV-IV; N=41) or subcutaneous (SC) 300mg miri Q4W (IV-SC; N=46). Due to small sample sizes, maintenance IV arms and SC arms were pooled. W12 SES-CD non-improvers (N=30) and pts receiving PBO during induction (N=59) received IV 1000mg miri Q4W from W12 to W48. No statistical comparisons were made between miri treatment groups in the maintenance period. SF-36 was assessed at baseline and at W4,12,16, 24, 32, 44, and 52. Results: Statistically significant improvement in MCS was observed at W4 (600mg dose level) and at W12 (all dose levels), whereas statistically significant improvements in PCS were observed only at W12 (600 and 1000mg dose levels) compared to PBO (Table). Though statistical comparisons were not made between treatment groups during maintenance, comparison of mean changes in MCS and PCS suggest that improvements during induction were sustained or further numerically increased with miri maintenance treatment, even in induction SES-CD non-improvers (Table). Conclusion: These data show that miri treatment improves health related quality of life in pts with moderately to severely active CD and suggest an earlier impact on mental compared to physical wellbeing. Maintenance treatment effects were numerically consistent or increased compared to induction effects, even among more refractory pts. These findings will be validated in the ongoing miri Ph3 CD study (NCT03926130). Proinflammatory signals can induce anxiety and depressive symptoms; better understanding of how the effects of anti-inflammatory treatment on the gut-brain axis may improve mental and physical subjective wellbeing requires additional mechanistic studies. Table 1. - Effect of mirikizumab on SF-36 MCS and PCS Change from Baseline Mental Component Score (MCS) Physical Component Score (PCS) Induction Period PBO (N=64) 200 mg IV miri (N=31) 600 mg IV miri (N=32) 1000 mg IV miri (N=64) PBO (N=64) 200 mg IV miri (N=31) 600 mg IV miri (N=32) 1000 mg IV miri (N=64) W0 Baseline (Mean ± SD) 37.0 ± 13.2 35.2 ± 10.2 41.1 ± 10.4 40.4 ± 11.6 38.9 ± 8.3 38.4 ± 6.4 42.9 ± 7.8 39.5 ± 8.6 W4 CFBL (LSM ± SE) 1.9 ± 1.0 2.6 ± 1.4 5.2 ± 1.4* 3.1 ± 1.0 2.4 ± 0.7 3.3 ± 1.0 3.4 ± 1.0 4.2 ± 0.7 W12 CFBL (LSM ± SE) 2.3 ± 1.1 7.5 ± 1.6* 6.5 ± 1.6* 6.1 ± 1.2* 3.1 ± 0.8 4.7 ± 1.1 8.0 ± 1.1** 6.7 ± 0.8** Maintenance Period PBO-1000 mg IV miri (N=59) NI-1000 mg IV miri (N=30) All IV-IV miri (N=41) All IV-SC miri (N=46) PBO-1000 mg IV miri (N=59) NI-1000 mg IV miri (N=30) All IV-IV miri (N=41) All IV-SC miri (N=46) W0 Baseline (Mean ± SD) 37.2 ±13.0 38.0 ±11.2 42.0 ± 10.1 38.7 ±10.7 39.5 ± 8.1 40.8 ± 8.3 41.1 ± 8.5 38.1 ± 7.1 W24 CFBL (Mean ± SD) 7.4 ± 8.7 7.7 ± 11.7 7.0 ± 10.6 5.9 ± 13.1 6.8 ± 7.3 7.1 ± 7.8 9.6 ± 5.6 7.1 ± 8.3 W52 CFBL (Mean ± SD) 7.1 ± 10.6 7.3 ± 9.8 8.5 ± 11.3 11.5 ± 11.4 9.9 ± 7.2 7.1 ± 8.2 10.2 ± 8.7 10.7 ± 7.9 Abbreviations: CFBL = change from baseline; IV = intravenous; IV-IV = pooled maintenance IV treatment arms for patients at each miri induction dose level who achieved ≥1-point improvement in SES-CD at W12 who were re-randomized to continued induction IV treatment assignment during maintenance; IV-SC = pooled maintenance SC treatment arms for patients at each miri induction dose level who achieved ≥1-point improvement in SES-CD at W12 who were re-randomized to SC 300mg miri Q4W during maintenance; LSM = least squares mean; NI = SES-CD non-improver (a patient who received miri during induction who did not achieve a ≥1-point improvement in SES-CD at W12); PBO = placebo; SC = subcutaneous; SD = standard deviation; SE = standard error; W = week. For statistical comparisons across induction treatment groups, a mixed model for repeated measures was used. The model includes treatment, region, prior biologic CD therapy used, baseline, visit and baseline by visit, and treatment by visit.p-values versus PBO: *p< 0.05; ** p≤0.001. Bolded values are statistically different versus PBO.

Correlation between magnetic resonance enterography and ileo-colonoscopy for assessment of disease activity in terminal ileal Crohn's disease.

Magnetic resonance enterography (MRE) has emerged as a novel tool for the assessment of disease activity in Crohn's disease (CD). Real world data from Indian subcontinent on performance of MRE in terminal ileal CD are lacking. Retrospective analysis of patients with terminal ileal CD who underwent both ileo-colonoscopy and MRE was performed. Ileo-colonoscopy was considered the gold standard for assessment of disease activity. On ileo-colonoscopy, a simple endoscopic score for Crohn's disease (SES-CD) ≥2 was considered active disease; presence of ulcers indicated severe disease. MRE scoring of the disease activity was performed using magnetic resonance index of activity (MARIA) and simplified MARIA (MARIAs). The measure of agreement between ileo-colonoscopy and MRE and comparison of MARIA and MARIAs for assessment of disease activity and sensitivity of MRE to detect mucosal ulcerations were calculated. Seventy patients with terminal ileal CD (mean age 40.74±15.56 years; 71.4% males [n=50]) were evaluated. The sensitivities of MARIA and MARIAs scores to detect active disease were 0.76 and 0.84, respectively. The area under the receiver operating characteristic curve (AUROC) for detecting severe disease was 0.836 (p<0.0001) for MARIA and 0.861 (p<0.0001) for MARIAs. For mild active disease, there was no agreement between SES-CD and MARIA or MARIAs; however, for severe disease, the agreement was fair and moderate for MARIA and MARIAs, respectively. MARIA and MARIAs were comparable for identification of active and severe disease (κ 0.759, p<0.0001 and κ 0.840, p<0.0001, respectively). MRE was 68.18% sensitive to detect mucosal ulcers. MRE is a reliable and sensitive tool for detection of endoscopically severe, but not mild, terminal ileal CD.

S814 Bile Acid Malabsorption Is a Common Risk Factor for Diarrhea in Adults With Mucosal Healing in Crohn’s Disease

Introduction: Bile acid malabsorption (BAM) accounts for over one-quarter of patients with diarrhea-predominant irritable bowel syndrome (IBS-D) and chronic diarrhea. However, the prevalence of BAM in adults with Crohn’s disease (CD) independent of ileal resection is not well characterized. We herein aim to identify the prevalence of BAM and determine its associations with diarrhea in adults with mucosal healing of CD on ileocolonoscopy. Methods: We analyzed a prospective cohort of adults with CD enrolled at a single institution biobank who underwent ileocolonoscopies from Jun 2014 to Mar 2021. Exclusion criteria were isolated upper GI CD (n=1) or prior bowel resection (n=9). Diarrhea was defined as an average of >3 liquid or very soft stools per day (SF>3) on the 2-item patient-reported outcome (PRO-2) measure over a 7-day period starting 48 hours before beginning bowel preparation. Endoscopic remission was defined as ≤2 on the Simple Endoscopic Score for Crohn's Disease (SES-CD). Histologic remission was defined as Geboes score < 2B.0 on biopsies from pre-determined ileocolonic segments (terminal ileum; ascending, descending, and rectosigmoid colon). Serum concentrations of 7α-hydroxy-4-cholesten-3-one (7C4), a precursor bile acid synthesis, were measured by liquid chromatography and mass spectrometry (Prometheus Laboratories) with BAM defined as a concentration ≥48.3 ng/mL (PMID: 30448597). We performed univariable analysis (χ2) and multivariable logistic regression to identify factors associated with diarrhea. Results: In 181 patients with CD in endoscopic remission, 29% (53/181) had diarrhea, and 29% (40/136) of those with 7C4 testing had BAM. Increased risk for diarrhea existed among those with BAM (OR 4.6, 95% CI 2.1-10.3, p< 0.01) and females (OR 2.2, 95% CI 1.1-4.3, p=0.02) (Table). On multivariate analysis, only BAM was a predictor of diarrhea (aOR 4.0, 95% CI 1.5-10.8, p< 0.01), but gender, ethnicity, and CD phenotype/location/duration were not predictors (Figure). Of the 57 patients with CD in endoscopic and histologic (endo-histologic) remission, BAM remains a risk factor for diarrhea (26%, 15/57; OR 35.8, 95% CI 6.9-184.2, p< 0.01). Conclusion: Bile acid malabsorption occurred in 29% and 26% of our cohort of adults with Crohn’s disease in endoscopic remission and endo-histologic remission, respectively, and conferred a 4-fold increased risk for diarrhea despite mucosal healing in Crohn’s disease.Figure 1.: Multivariable analysis of factor associated with diarrhea in adults with Crohn’s disease in endoscopic remission Key: aOR; adjusted odds ratio. CD, Crohn’s disease. Multivariable analysis of factor associated with diarrhea in adults with Crohn’s disease in endoscopic remission. Independent variables gender, ethnicity; CD phenotype, location, duration; and bile acid malabsorption. Dependent variable: diarrhea (SF >3) or diarrhea (stool frequency, SF >3). Table 1. - Crohn’s disease in Endoscopic remission (N=181) Characteristics n (%) Diarrhea (n=53) No Diarrhea (n=128) p-value OR (95% CI) p-value Gender 0.02 Female 36 (68%) 63 (49%) 2.2 (1.1-4.3) 0.02 Male 17 (32%) 65 (51%) Ref / Ethnicity 0.38 Caucasian Non-Caucasian 39 (74%) 101 (80%) 0.7 (0.3-1.5) 0.38 Missing n=1 14 (26%) 26 (20%) Ref / CD phenotype 0.08 Inflammatory Stricturing 18 (43%) 65 (63%) Ref / Fistulizing 12 (29%) 20 (19%) 2.2 (0.9-5.3) 0.0871 Missing n=36 12 (29%) 18 (17%) 2.4 (1.0-5.9) 0.0551 CD disease location Ileal Colonic Ileocolonic Missing n=22 0.14 22 (47%) 36 (32%) 1.5 (0.6-3.4) 0.38 14 (28%) 31 (28%) Ref / 12 (26%) 45 (40%) 0.6 (0.3-1.6) 0.33 CD duration 11 (21%)16 (31%)25 (48%) 31 (25%)51 (41%)43 (63%) 0.23 Ref0.9 (0.4-2.1)1.6 (0.7-3.8) /0.790.25 < 5 years 5-15 years >15 years Missing n=4 Bile acid malabsorption < 0.01 < 0.01 Yes No 22 (52%) 18 (19%) 4.6 (2.1-10.3) Missing n=45 20 (48%) 76 (81%) Ref Key: CD, Crohn’s disease; OR, odds ratio.

Ulcer Size After Induction Therapy Performs Better Than Symptom Assessment for Prediction of One Year Endoscopic Remission in Crohn's Disease: A Post Hoc Analysis.

We evaluated whether postinduction ulcer size and patient-reported outcome (PRO) severity are associated with the achievement of 1-year endoscopic remission (ER) in patients with Crohn's disease (CD). This post hoc analysis combined data from several clinical trials including 283 patients with baseline ulcers ≥5 mm with repeat endoscopy after ustekinumab or adalimumab induction therapy. Patient-reported outcomes including stool frequency (SF) and abdominal pain (AP) were measured by the Crohn's Disease Activity Index. Thresholds of SF ≥4 and/or AP ≥2 indicated moderately to severely active CD. Endoscopic remission was defined as Simple Endoscopic Score for CD (SES-CD) <3. Multivariate logistic regression models adjusted for confounders (including disease duration and treatment allocation) evaluated the relationships between postinduction ulcer size, PRO symptoms, and achievement of 1-year ER. Among the 131 CD patients who continued to have ulcers ≥5 mm after induction therapy, 48 (36.6%) achieved 1-year ER. Patients with postinduction ulcers ≥5 mm were approximately 5 times less likely to achieve 1-year ER than the 152 individuals who had small or no postinduction ulcers (odds ratio [OR], 0.20; 95% CI, 0.08-0.51, P = .001). In patients with ulcers ≥5 mm after induction, postinduction PRO scores (including PRO2 and PRO3) did not predict 1-year ER. Crohn's disease patients with ulcers ≥5 mm after induction therapy are less likely to achieve 1-year ER. Postinduction PRO severity does not offer additional prognostic information. This may suggest that objective measures of disease such as endoscopic ulcer size should be considered over symptom assessments for determining clinical response to therapy and utilized in trials for maintenance therapy.

Pediatric Patient and Caregiver Satisfaction With the Use of Transabdominal Bowel Ultrasound in the Assessment of Inflammatory Bowel Diseases.

Transabdominal bowel ultrasound (TABUS) is emerging as an attractive, noninvasive tool in inflammatory bowel disease (IBD). Patient and caregiver experience with TABUS is not well described. We aimed to determine pediatric patient and caregiver satisfaction with TABUS and the impact of IBD severity, gender, age, and a history of anxiety on satisfaction. Pediatric patients (0-18 years old) with suspected IBD prospectively underwent baseline TABUS, magnetic resonance enterography (MRE), blood work, stool studies, and endoscopy. Patients and their caregiver each completed a cross-sectional satisfaction questionnaire (5-point Likert scale) after the baseline investigations. There were 54 patients included (67% male). The majority were completely satisfied and strongly agree TABUS was better tolerated than other investigations, regardless of disease severity ( P > 0.05). Patients with higher Simple Endoscopic Score for Crohn Disease (SES-CD) scores felt that TABUS increased their understanding of their IBD ( P < 0.05) and disease location ( P < 0.05). Patients with Crohn disease had similar responses to those with ulcerative colitis, but more strongly agreed that TABUS was better than MRE and endoscopy ( P < 0.05). Those with anxiety did not have an increased level of worry about potential ultrasound findings ( P > 0.05). Pediatric patients and their caregivers were highly satisfied with TABUS, preferring it to other modalities. It did not lead to increased worry, and was particularly important in those with severe IBD. These findings support wider implementation of this well tolerated and preferred monitoring tool in pediatrics.

Pilot study of an elimination diet in adults with mild to moderate Crohn's disease.

There remains limited data supporting the efficacy of dietary therapy in adults with Crohn's disease (CD). This was a pilot study of the McMaster Elimination diet for CD (MED-CD), which excludes several potentially detrimental ingredients commonly found in the Western diet. Prospective study in adults with mild-moderately active CD [Harvey-Bradshaw Index (HBI) scores 5-16] and endoscopic disease activity of &gt;7 (or ≥4 for isolated ileal disease) as measured by the Simple Endoscopic Score for Crohn's disease (SES-CD). Patients were treated for 2 weeks using oral enteral nutrition (EN). Those with symptomatic improvement (HBI score reduction ≥2) were transitioned to the MED-CD for 12 weeks. Outcomes of interest included satisfactory adherence (≥20 on the modified medical adherence report scale-5 questionnaire), clinical remission (CR) (HBI ≤4), clinical response (HBI reduction ≥3), endoscopic response (SES-CD reduction ≥50%), and endoscopic remission (ER) (SES-CD &lt;3). A total of 17 patients were treated with 2 weeks of EN. Of these, 13 were deemed responders and treated with 12 weeks of MED-CD. Satisfactory adherence was reported among 11/13 (84.6%) at week 6 and 8/12 (67%) at week 14. Of the 13 patients who responded to EN by week 2, 5 (38.5%) had attained CR at week 2 and maintained CR until week 14 using MED-CD. Endoscopic response was observed in 6 (46.2%) participants and ER was seen in 2 (15.4%). Two weeks of oral EN followed by 12 weeks of the MED-CD was acceptable by most adult patients who enroled in this study.

The endoscopic prediction model of simple endoscopic score for Crohn's disease (SES-CD) as an effective predictor of intestinal obstruction in Crohn's disease: A multicenter long-term follow-up study.

The simple endoscopic score for Crohn's disease (SES-CD) is a widely used index to evaluate clinical and endoscopic activity. However, the association and predictive value of SES-CD for intestinal obstruction in Crohn's disease (CD) remains unclear. We aimed to establish the best cut-off indicators of SES-CD for early clinical intervention and subsequent prevention of intestinal obstruction in CD. Data on patients with CD evaluated at our institute from January 2016 to January 2022 were retrospectively collected. The SES-CD and Crohn's Disease Activity Index scores used in the analysis indicated the results of the first clinical and colonoscopy evaluations after hospitalization. The primary outcome was the occurrence of intestinal obstruction during admission and follow-up. A total of 248 patients with a median follow-up time of 2years [interquartile range: 1.0-4.0] were enrolled, of which 28.2% developed intestinal obstruction. An SES-CD score of 8 was the most significant threshold evaluation, and SES-CD ≥8 had the largest area under the receiver operating characteristic curve (0.705), with a sensitivity of 52.9% and specificity of 88.2% in predicting intestinal obstruction. Furthermore, SES-CD ≥8 had the greatest risk factor for intestinal obstruction (odds ratio: 7.731; 95% confidence interval: 3.901-15.322; p < 0.001) and significantly decreased the overall intestinal obstruction-free survival (p < 0.001). The SES-CD endoscopic prediction model could be an effective predictor of intestinal obstruction in patients with CD. More frequent follow-up and colonoscopic surveillance should be considered in patients with SES-CD score ≥8 to prevent the development of intestinal obstruction.

Validating the Simplified Endoscopic Mucosal Assessment for Crohn's Disease: A Novel Method for Assessing Disease Activity.

To demonstrate treatment efficacy in Crohn's disease (CD), regulatory authorities require that trials include an endoscopic remission/response end point; however, standardized endoscopic assessment of disease activity, such as the Simple Endoscopic Score for Crohn's Disease (SES-CD), is not typically recorded by clinicians in practice or outside of clinical trials. The novel Simplified Endoscopic Mucosal Assessment for Crohn's Disease (SEMA-CD) was developed to be easy to use in routine clinical practice and as a trial end point. We conducted a study to assess and validate the reliability and feasibility of SEMA-CD as a measure of endoscopic disease activity. Pre- and post-treatment ileocolonoscopy videos of pediatric (n = 36) and adult (n = 74) CD patients from 2 ustekinumab clinical trials were each scored with SEMA-CD by 2 to 3 professional central readers, blinded to clinical history and other video scorings; the correlation between SEMA-CD and SES-CD previously completed during the trials was assessed. Sensitivity to change, inter- and intrarater reliability, and comparative ease of scoring were also assessed. The SEMA-CD strongly correlated with SES-CD (Spearman ρ = 0.89; 95% confidence interval, 0.86-0.92). Pre- to post-treatment changes in SEMA-CD vs in SES-CD were strongly correlated, and the correlation remained strong between the scores when compared by study population (pediatric, adult), disease severity, and video quality. Intra- and inter-rater reliability were good, and SEMA-CD was rated easier than SES-CD to score 63.0% of the time, although slightly more difficult than SES-CD to score <1.0% of the time. The SEMA-CD is reliable, reproducible, sensitive to change, and easy to use in both pediatric and adult patients with CD.

Adalimumab versus ustekinumab as first-line biological in moderate-to-severe Crohn's disease: real-life cohort from a tertiary referral center.

Therapeutic options for Crohn's disease are growing, making the choice of first-line therapy relevant. Both adalimumab and ustekinumab are effective in moderate-to-severe Crohn's disease. The Safety and Efficacy of Adalimumab Versus Ustekinumab for One Year trial suggested no difference in clinical or endoscopic remission at week 52 in biological-naive Crohn's disease patients. We explored if results withstand in the real world. We included bio-naive Crohn's disease patients starting adalimumab or ustekinumab between 2017 and 2020. Patients had endoscopy-proven moderate-to-severe disease [Simple Endoscopic Score for Crohn's disease (SES-CD) ≥3]. Clinical remission was defined as Harvey Bradshaw Index (HBI) <5 or physician global assessment. Endoscopic remission (SES-CD <3) and improvement (≥50% reduction in SES-CD from baseline) were assessed at W26-52. Propensity score matching was used. A total of 68 biological-naive Crohn's disease patients were included (32 adalimumab and 32 ustekinumab) and followed for median of (IQR) 60 (33-104) weeks. Patients had significantly higher odds of achieving endoscopic remission with adalimumab than ustekinumab [adjusted odds ratio (aOR), 2.73; confidence interval (CI), 1.12-7.36; P = 0.03]. Also, more adalimumab-treated patients achieved endoscopic response, clinical remission at week 26 and 52 (aOR, 2.24; CI, 0.94-5.71; P = 0.07; aOR, 1.26; CI, 0.36-4.51; P = 0.72; aOR, 1.58; CI, 0.54-4.88; P = 0.41, respectively). Treatment persistence was not different between groups (P = 0.44). The number of adverse events was similar. In a real-world cohort of biological-naive Crohn's disease patients, adalimumab was superior to ustekinumab in achieving endoscopic remission. No differences in clinical remission at W26-52 or treatment persistence were observed. Both adalimumab and ustekinumab remain good options as first-line biologicals in moderate-to-severe Crohn's disease.

Contrast-enhanced ultrasound in the assessment of Crohn’s disease activity: comparison with computed tomography enterography

Continuous assessment of disease activity remains a huge challenge during the follow-ups of patients with Crohn's disease (CD). In this paper, we aimed to evaluate the performance of contrast-enhanced ultrasound (CEUS) by comparing with computed tomography enterography (CTE) in the assessment of disease activity in CD. Fifty-two patients diagnosed with CD were included in this study, using the CEUS and CTE as imaging methods for comparison. The selected parameters included the location and thickness of the thickest part of the intestinal wall, mesenteric fat proliferation, mesenteric vessels change, enhancement pattern and the presence of complications. Patients were clinically assessed using the Crohn's disease activity index (CDAI), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Simple endoscopic score for Crohn's disease (SES-CD) was regarded as the reference standard. The location of the thickest part of the intestinal wall (κ = 0.653), bowel wall thickness (ICC = 0.795), mesenteric vessels change (κ = 0.692) and complications (κ = 0.796) displayed substantial agreement (0.61-0.80) between CEUS and CTE, while the detection of mesenteric fat proliferation (κ = 0.395) and enhancement pattern (κ = 0.288) showed fair consistency (0.21-0.40) for comparison. In CEUS, bowel wall thickness, mesenteric fat proliferation, enhancement pattern and mesenteric vessels change were statistically significant in assessing CD activity, while bowel wall thickness, mesenteric fat proliferation and mesenteric vessels change in CTE. Bowel wall thickness showed the best diagnostic performance in the assessment of CD activity at CEUS and CTE. CEUS provides a radiation-free and effective way to assess the CD activity in comparison with CTE, which also avoids frequent colonoscopy examinations, improves tolerance of patients, and reduces the cost of medical care, thereby serving as a useful tool for CD follow-up.

Fecal Calprotectin, Chitinase 3-Like-1, S100A12 and Osteoprotegerin as Markers of Disease Activity in Children with Crohn’s Disease

Fecal calprotectin (FC), chitinase 3-like-1 protein (CHI3L1), S100A12 and osteoprotegerin (OPG) are biomarkers of intestinal inflammation. This cross-sectional study aimed to evaluate these biomarkers in a cohort of children with Crohn’s disease (CD) and compare them with other measures of disease activity. Stool samples from children with CD were used to measure FC, CHI3L1, S100A12 and OPG by enzyme-linked immunosorbent assay. Serum inflammatory markers were measured and pediatric CD disease activity index (PCDAI) scores calculated. The simple endoscopic score for CD (SES-CD) was reported for a subgroup who underwent ileocolonoscopy corresponding with the stool samples. Sixty-five children were recruited. Children in clinical remission had lower FC and CHI3L1 levels than those with active disease (FC: 277 vs. 1648 µg/g, p = 0.012; CHI3L1: 23 vs. 227 ng/g, p = 0.013). FC levels differed between patients with clinically active or inactive isolated ileal CD. Although FC and CHI3L1 levels correlated strongly (r = 0.83), none of the fecal markers correlated well with serum markers. Only FC and OPG correlated with SES-CD scores (r = 0.57 and r = 0.48, respectively). In conclusion, FC correlated with both endoscopic and clinical disease activity and was the only biomarker that differentiated between active and inactive ileal CD. CHI3L1 also predicted clinical disease activity and correlated highly with FC. Further investigation of the role of CHI3L1 is required.

Faecal Myeloperoxidase as a Biomarker of Endoscopic Activity in Inflammatory Bowel Disease.

Inflammatory bowel disease [IBD], consisting of Crohn's disease [CD] and ulcerative colitis [UC], is a relapsing-remitting illness. Treat-to-target IBD management strategies require monitoring of gastrointestinal inflammation. This study aimed to investigate faecal myeloperoxidase [fMPO], a neutrophil granule enzyme, as a biomarker of IBD activity. Prospectively recruited participants with IBD, undergoing ileocolonoscopy for disease assessment, provided biological samples and completed symptom questionnaires prior to endoscopy. fMPO, C-reactive protein [CRP], and faecal calprotectin [fCal] were compared with validated endoscopic indices [simple endoscopic score for CD and UC endoscopic index of severity]. Receiver operating characteristic [ROC] curves assessed the performance of fMPO, CRP, and fCal in predicting endoscopic disease activity. Baseline biomarkers were used to predict a composite endpoint of complicated disease at 12 months [need for escalation of biologic/immunomodulator due to relapse, steroid use, IBD-related hospitalisation, and surgery]. A total of 172 participants were recruited [91 female, 100 with CD]. fMPO was significantly correlated with endoscopic activity in both CD [r = 0.53, p < 0.01] and UC [r = 0.63, p < 0.01], and with fCal in all patients with IBD [r = 0.82, p < 0.01]. fMPO was effective in predicting moderate-to-severely active CD [AUROC 0.86, p < 0.01] and UC [AUROC 0.92, p < 0.01]. Individuals with a baseline fMPO > 26 µg/g were significantly more likely to reach the composite outcome at 12 months (hazard ratio [HR] 3.71, 95% confidence interval [CI] 2.07-6.64, p < 0.01). Faecal myeloperoxidase is an accurate biomarker of endoscopic activity in IBD and predicted a more complicated IBD course during follow-up.

Diagnostic Value of Quantitative Contrast-Enhanced Ultrasound in Comparison to Endoscopy in Children With Crohn's Disease.

Quantitative contrast-enhanced US (CEUS) provides objective evaluation of bowel wall perfusion and has been reported as a useful method for evaluating Crohn's disease (CD) activity in children. We tested its' diagnostic accuracy in comparison to endoscopy and evaluated its' usefulness in comparison to Pediatric Crohn's Disease Activity Index (PCDAI) and fecal Calprotectin (FC). Children with CD and thickened bowel wall on abdominal US were prospectively enrolled. Disease activity was evaluated with quantitative CEUS, PCDAI and FC and compared to a simple endoscopic score for Crohn's disease (SES-CD). Spearman's correlation and Cohen's kappa statistic between the SES-CD and other disease activity measures were performed and diagnostic accuracies calculated. 36 children 3.5-18 years old (mean age 14 years) were included. The quantitative CEUS had 78.57% sensitivity (95%CI 0.59-0.92), 100% specificity (95%CI 0.63-1.0) and 83.33% diagnostic accuracy (95% CI 0.67-0.94). The concordance remission agreement with endoscopy was substantial for quantitative CEUS and PCDAI (quantitative CEUS: κ=0.62; 95% CI 0.363-0.877; PCDAI: κ=0.615; 95% CI 0.311-0.920), but only fair for FC (κ=0.389; 95% CI 0.006-0.783). Correlation between all measures and endoscopy was moderate and statistically significant (quantitative CEUS: rs =0.535, PCDAI: rs =0.543, FC: rs =0.497). Quantitative CEUS has a potential of becoming a complementary method for evaluation of CD activity in children due to its' high specificity in comparison to endoscopy. Lower sensitivity makes it deficient as a single measure and further management should be guided by PCDAI and FC results as well.

A Serum Biomarker Panel Can Accurately Identify Mucosal Ulcers in Patients With Crohn's Disease.

The Endoscopic Healing Index (EHI) is a serum biomarker panel that can predict endoscopic inflammation in Crohn's disease (CD). Paired serum samples with endoscopies from adult patients participating in a prospective biobank (June 2014 to December 2018) were analyzed post hoc. Diagnostic performance for EHI was assessed against the individual parameters of the Simple Endoscopic Score for CD using previously identified cutoffs. Confounders for EHI performance were identified using logistic regression. A total of 205 CD patients were included (50% male, median age 37 years). An EHI of 20 points was sensitive for ruling out any ulcers (85%; 95% confidence interval [CI], 77%-91%) and large (5-20 mm) or very large (>20 mm) ulcers (93%; 95% CI, 84%-97%). An EHI of 50 points was specific for ruling in any ulcers (86%; 95% CI, 76%-92%) and large or very large ulcers (87%; 95% CI, 79%-92%). After accounting for total extent of inflamed mucosa, strictures, and disease location, each 20-point increase in EHI was associated with a 1.7-fold increased probability for the presence of large or very large ulcers (adjusted odds ratio, 1.7; 95% CI, 1.1-2.6). The EHI was independently associated with ulcer size and accurately identified large or very large ulcers. A cutoff of 50 points can reliably rule in mucosal ulcers and allow for treatment adjustment. A cutoff of 20 points can reliably rule out mucosal ulcers and signal completion of treatment adjustment algorithms.

The SES-CD Could Be a Predictor of Short- and Long-Term Mucosal Healing After Exclusive Enteral Nutrition in Pediatric Crohn's Disease Patients.

AimsTo explore the predictors of mucosal healing (MH) for short- and long-term after exclusive enteral nutrition (EEN) in pediatric Crohn’s disease (CD) patients.MethodsA retrospective analysis was performed for newly diagnosed active CD patients admitted to our center from January 2017 to 30 December 2020, who were treated with EEN for induction therapy with a minimum of 12 months of follow-up post-EEN. According to the simple endoscopic score for CD (SES-CD), at 1-year post-EEN, 17 patients with an SES-CD < 3 were classified into the sustained MH group (sMH), and 33 patients with an SES-CD ≥ 3 were classified into the sustained non-MH group (sNMH). Statistical methods were used to compare the differences between the two groups and explore the predictors of MH at the end of EEN and 1-year post-EEN.ResultsThe SES-CD in the sMH group was lower than that in the sNMH group both at baseline and the end of EEN [sMH vs. sNMH: 8.7 ± 1.2 vs. 16.2 ± 1.0, respectively, p < 0.001 at baseline; 1.0 (3.5) vs. 4.0 (2.0), respectively, p < 0.01 at the end of EEN]. The weighted Pediatric Crohn’s Disease Activity Index and erythrocyte sedimentation rate in the sMH group were lower than those in the sNMH group at baseline (both p < 0.05), but showed no difference at the end of EEN. From baseline to 1-year post-EEN, compared with patients in the sNMH group, there were more patients classified with L1 in the sMH group at each time point (all p < 0.001) and fewer patients classified with L3 in the sMH group at baseline and 1-year post-EEN. After EEN, fewer patients received infliximab and had a longer exposure time to infliximab in the sMH group than in the sNMH group. Only the SES-CD at baseline was negatively associated with MH at the end of EEN (OR = 1.40 95% CI = 1.12–1.67, p = 0.00) and 1-year post-EEN (OR = 1.33, 95% CI = 1.12–1.58, p = 0.001), and the cut off value was 11.5.ConclusionThe SES-CD could predict both short- and long-term MH for EEN. Patients with an SES-CD < 11.5 had a high probability of reaching MH by EEN-inducing therapy and maintaining sustained MH at 1-year post-EEN. Patients with an SES-CD greater than 11.5 at baseline should be treated more aggressively with biologics.

Ultrasonographic scores for ileal Crohn’s disease assessment: Better, worse or the same as contrast-enhanced ultrasound?

BackgroundIntestinal ultrasound (IUS) is an increasingly used non-invasive tool to evaluate Crohn’s disease (CD) activity. Recently, two IUS scores that evaluate inflammatory activity have emerged: the Simple Ultrasound Activity Score for CD (SUS-CD) and the International Bowel Ultrasound Segmental Activity Score (IBUS-SAS). We aimed to compare the accuracy of SUS-CD, IBUS-SAS and contrast-enhanced ultrasound (CEUS) in predicting inflammatory activity in the terminal ileum in ileocolonoscopy in CD patients.MethodsRetrospective study including all consecutive CD patients submitted to IUS with CEUS directed to the terminal ileum performed by a single operator between April 2016 and March 2020. Segmental SUS-CD and IBUS-SAS were calculated. A time-intensity curve of the contrast bowel wall enhancement was created with measurement of peak intensity using CEUS. The CD endoscopic activity in ileocolonoscopy was graded by Simple Endoscopic Score for CD (SES-CD) as inactive (SES-CD < 7) or active (SES-CD ≥ 7).ResultsFifty patients were included, 54.0% were female, with mean age of 34 ± 12 years, and most had isolated ileal disease (60.0%), and a nonstricturing, nonpenetrating behaviour (44.0%). Most of the patients (60.0%) had active endoscopic disease (SES-CD ≥ 7). SUS-CD and IBUS-SAS were not different between patients with active or inactive endoscopic disease (p = 0.15; 0.57, respectively), having a poor accuracy to correlate endoscopic activity (area under de curve (AUC) 0.62; 0.55, respectively). Peak intensity in CEUS was significantly different in patients with active or inactive endoscopic disease (p = 0.004), having a good accuracy to correlate endoscopic activity (AUC 0.80).ConclusionUnlike CEUS, SUS-CD and IBUS-SAS were not able to accurately correlate endoscopic activity in terminal ileum in CD. Therefore, CEUS is a non-invasive emerging method that should be increasingly integrated in the ultrasonographic evaluation of CD patients.

Risankizumab as induction therapy for Crohn's disease: results from the phase 3 ADVANCE and MOTIVATE induction trials

Risankizumab, an interleukin (IL)-23 p19 inhibitor, was evaluated for safety and efficacy as induction therapy in patients with moderately to severely active Crohn's disease. ADVANCE and MOTIVATE were randomised, double-masked, placebo-controlled, phase 3 induction studies. Eligible patients aged 16-80 years with moderately to severely active Crohn's disease, previously showing intolerance or inadequate response to one or more approved biologics or conventional therapy (ADVANCE) or to biologics (MOTIVATE), were randomly assigned to receive a single dose of intravenous risankizumab (600 mg or 1200 mg) or placebo (2:2:1 in ADVANCE, 1:1:1 in MOTIVATE) at weeks 0, 4, and 8. We used interactive response technology for random assignment, with stratification by number of previous failed biologics, corticosteroid use at baseline, and Simple Endoscopic Score for Crohn's disease (SES-CD). All patients and study personnel (excluding pharmacists who prepared intravenous solutions) were masked to treatment allocation throughout the study. Coprimary endpoints were clinical remission (defined by Crohn's disease activity index [CDAI] or patient-reported outcome criteria [average daily stool frequency and abdominal pain score]) and endoscopic response at week 12. The intention-to-treat population (all eligible patients who received at least one dose of study drug in the 12-week induction period) was analysed for efficacy outcomes. Safety was assessed in all patients who received at least one dose of study drug. Both trials were registered on ClinicalTrials.gov, NCT03105128 (ADVANCE) and NCT03104413 (MOTIVATE), and are now complete. Participants were enrolled between May 10, 2017, and Aug 24, 2020 (ADVANCE trial), and Dec 18, 2017 and Sept 9, 2020 (MOTIVATE trial). In ADVANCE, 931 patients were assigned to either risankizumab 600 mg (n=373), risankizumab 1200 mg (n=372), or placebo (n=186). In MOTIVATE, 618 patients were assigned to risankizumab 600 mg (n=206), risankizumab 1200 mg (n=205), or placebo (n=207). The primary analysis population comprised 850 participants in ADVANCE and 569 participants in MOTIVATE. All coprimary endpoints at week 12 were met in both trials with both doses of risankizumab (p values ≤0·0001). In ADVANCE, CDAI clinical remission rate was 45% (adjusted difference 21%, 95% CI 12-29; 152/336) with risankizumab 600 mg and 42% (17%, 8-25; 141/339) with risankizumab 1200 mg versus 25% (43/175) with placebo; stool frequency and abdominal pain score clinical remission rate was 43% (22%, 14-30; 146/336) with risankizumab 600 mg and 41% (19%, 11-27; 139/339) with risankizumab 1200 mg versus 22% (38/175) with placebo; and endoscopic response rate was 40% (28%, 21-35; 135/336) with risankizumab 600 mg and 32% (20%, 14-27; 109/339) with risankizumab 1200 mg versus 12% (21/175) with placebo. In MOTIVATE, CDAI clinical remission rate was 42% (22%, 13-31; 80/191) with risankizumab 600 mg and 40% (21%, 12-29; 77/191) with risankizumab 1200 mg versus 20% (37/187) with placebo; stool frequency and abdominal pain score clinical remission rate was 35% (15%, 6-24; 66/191) with risankizumab 600 mg and 40% (20%, 12-29; 76/191) with risankizumab 1200 mg versus 19% (36/187) with placebo; and endoscopic response rate was 29% (18%, 10-25; 55/191) with risankizumab 600 mg and 34% (23%, 15-31; 65/191) with risankizumab 1200 mg versus 11% (21/187) with placebo. The overall incidence of treatment-emergent adverse events was similar among the treatment groups in both trials. Three deaths occurred during induction (two in the placebo group [ADVANCE] and one in the risankizumab 1200 mg group [MOTIVATE]). The death in the risankizumab-treated patient was deemed unrelated to the study drug. Risankizumab was effective and well tolerated as induction therapy in patients with moderately to severely active Crohn's disease. AbbVie.

Comparative Effectiveness of Biologics for Endoscopic Healing of the Ileum and Colon in Crohn's Disease.

We compared the efficacy of adalimumab, infliximab, ustekinumab, and vedolizumab on the ability to achieve endoscopic healing (EH) after 1 year of therapy in moderate-severe Crohn's disease (CD). This was a pooled analysis of patient-level data from 299 patients with CD from 4 clinical trials. Proportions of patients treated with each biologic were compared for achieving 1-year complete EH (Simple Endoscopic Score for CD [SES-CD] <3) and ileal and colonic EH separately (SES-CD = 0). Multivariate logistic regression was used to model the relationship between biologics and 1-year outcomes and adjusted for disease duration, concomitant corticosteroid use, and prior antitumor necrosis factor failure. Compared with vedolizumab (4/56 [7.1%]), adalimumab (17/61 [27.9%], adjusted odds ratio [OR]: 5.79, 95% confidence interval [CI]: 1.77-18.95, P = 0.004) and infliximab (39/141 [27.7%], aOR: 4.59, 95% CI: 1.48-14.22, P = 0.008) had superior rates of 1-year EH. No significant difference was observed between vedolizumab and ustekinumab. Similar results were observed among biologic-naive patients. Among patients with baseline ileal SES-CD ≥3, no significant differences were observed between biologics for 1-year ileal EH. However, for large (>0.5 cm) ileal ulcers, infliximab (20/49 [40.8%]) had superior rates of no ileal ulcers compared with vedolizumab (2/23 [8.7%], aOR: 5.39, 95% CI: 1.03-28.05, P = 0.045). No other differences were observed. For colonic disease, compared with ustekinumab (9/31 [29.0%]), adalimumab (30/48 [62.5%], aOR: 3.97, 95% CI: 1.45-10.90, P = 0.007) had superior rates of 1-year EH in the colon, with similar trends observed for infliximab (55/105 [52.4%], aOR: 2.08, 95% CI: 0.82-5.27, P = 0.121). No other differences were observed. In this post hoc analysis, TNF-α antagonists were overall superior to vedolizumab and ustekinumab for achieving 1-year EH in moderate-severe CD patients.

Correlation Between Crohn's Disease Activity and Serum Selenium Concentration

PurposeAccurate and reliable evaluation of Crohn's disease (CD) activity is crucial for monitoring and treating the disease; however, it is challenging. There is a high demand for new, reliable, and noninvasive biomarkers for estimating CD activity. Selenium deficiency is common in patients with CD; however, its correlation with disease severity remains unclear. This study aimed to assess the feasibility of using serum selenium concentration as an additional biomarker for determining the severity of CD. MethodsThis retrospective study included consecutive Asian patients aged 18 to 60 years and hospitalized for CD between May 2020 and December 2020 at the Inflammatory Bowel Disease Center (Hangzhou, China). Patients with a history of extensive small intestinal surgery and/or short bowel syndrome were excluded from analysis. Serum selenium concentration was determined using inductively coupled plasma mass spectrometry. Disease severity was evaluated based on inflammatory markers (simple endoscopic score for CD, CD activity index, Harvey-Bradshaw index, serum C-reactive protein level, erythrocyte sedimentation rate, and platelet count) and markers of nutrition status (body mass index; blood hemoglobin and hematocrit; as well as serum levels of albumin, folic acid, and vitamin D). The correlations between serum selenium level and disease severity–related parameters were analyzed using univariate and multivariate analyses. FindingsThe study included 94 men and 41 women. Serum selenium level was significantly and inversely associated with all tested disease activity–related parameters by univariate analysis (all, P < 0.05). Further multivariate analysis showed that the simple endoscopic score for CD and serum levels of albumin and folic acid were significantly and independently correlated with serum selenium level (all, P < 0.05). ImplicationsSerum selenium concentration was inversely correlated with endoscopic disease severity in these Asian patients with CD. It is feasible to use serum selenium level as an additional biomarker for assessing and monitoring disease activity. The present results might have been influenced by geographic region, sample size, and/or dietary factors. Serum selenium level and other indicators of CD activity measured before and after treatment may provide more useful clinical information.

Adalimumab vs Infliximab in Pediatric Patients With Crohn's Disease: A Propensity Score Analysis and Predictors of Treatment Escalation.

INTRODUCTION:Two antitumor necrosis factor therapies (infliximab [IFX] and adalimumab [ADA]) have been approved for the treatment of pediatric Crohn's disease (CD) but have not been compared in head-to-head trials. The aim of this study was to compare the efficacy and safety of ADA and IFX by propensity score matching in a prospective cohort of pediatric patients with luminal CD and at least a 24-month follow-up.METHODS:Among 100 patients, 75 met the inclusion criteria, and 62 were matched by propensity score. We evaluated time to treatment escalation as the primary outcome and primary nonresponse, predictors of treatment escalation and relapse, serious adverse events, pharmacokinetics, and effect of concomitant immunomodulators as secondary outcomes.RESULTS:There was no difference between ADA and IFX in time to treatment escalation (HR = 0.63 [95% CI 0.31–1.28] P = 0.20), primary nonresponse (P = 0.95), or serious adverse events. The median (interquartile range) trough levels at the primary outcome were 14.05 (10.88–15.40) and 6.15 (2.08–6.58) µg/mL in the ADA and IFX groups, respectively. On a multivariate analysis, the combination of anti-Saccharomyces cerevisiae antibody negativity and antineutrophil cytoplasmic antibody positivity was a strong independent predictor of treatment escalation (HR 5.19, [95% CI 2.41–11.18], P < 0.0001). The simple endoscopic score for CD, L3 disease phenotype, and use of concomitant immunomodulators for at least the first 6 months revealed a trend toward significance on a univariate analysis.DISCUSSION:Propensity score matching did not reveal substantial differences in efficacy or safety between ADA and IFX. The anti-S. cerevisiae antibody negativity and antineutrophil cytoplasmic antibody positivity combination is a strong predictor of treatment escalation.