Prospective Observational Evaluation of the Time-Dependency of Adalimumab Immunogenicity and Drug Concentration in Ulcerative Colitis Patients: the POETIC II Study.

BACKGROUND AND AIMS: Home self-injection of the human anti-tumour necrosis alpha [anti-TNFα] monoclonal adalimumab complicates prospective serial-sampling studies. Although a recent study examined adalimumab levels and immunogenicity in Crohn's disease [CD] patients, prospective real-world data from ulcerative colitis [UC] patients are lacking. METHODS: A three-monthly home-visit programme from induction was established prospectively for UC patients. Clinical scores were determined at each visit, and sera were obtained for assessment of drug and anti-adalimumab antibody levels. Calprotectin was measured using a smartphone-based app. This cohort was compared to a parallel prospective cohort of adalimumab-treated CD patients [POETIC1]. RESULTS: Fifty UC patients starting adalimumab [median follow-up 28 weeks] were compared to 98 adalimumab-treated CD patients [median follow-up 44 weeks]. Only 11/50 UC patients [22%] continued treatment to the end of the follow-up compared with 50/98 [51%] CD patients (odds ratio [OR] = 0.27, p = 0.001). Loss of response was significantly more common in UC patients [OR = 3.2, p = 0.001]. Seventeen patients [34%] in the UC cohort developed anti-adalimumab antibodies, 9/17 [52.9%] as early as week 2. There was no difference between patient cohorts in the overall development of anti-adalimumab antibodies [34% vs 30.6%, respectively, OR = 1.67, p = 0.67], nor was there a difference in early immunogenicity [OR = 1.39, p = 0.35]. There was no difference in low drug levels [<3 µg/mL] between the two cohorts [OR = 0.87, p = 0.83]. CONCLUSIONS: Loss of response to adalimumab therapy was significantly more common in the UC compared to the CD cohort and was driven by a higher rate of non-immunogenic, pharmacodynamic parameters.

Jejunal Inflammation in Crohn's Disease: Comparison between Diffusion Weighted Magnetic Resonance Imaging and Video Capsule Endoscopy.

BACKGROUND: Jejunal disease is associated with worse prognosis in Crohn's disease. The added value of diffusion weighted imaging for evaluating jejunal inflammation related to Crohn's Disease is scarce. OBJECTIVES: To compare diffusion weighted imaging, video capsule endoscopy, and inflammatory biomarkers in the assessment of Crohn's disease involving the jejunum. METHODS: Crohn's disease patients in clinical remission were prospectively recruited and underwent magnetic resonance (MR)-enterography and video capsule endoscopy. C-reactive protein and fecal-calprotectin levels were obtained. MR-enterography images were evaluated for restricted diffusion, and apparent diffusion coefficient values were measured. The video capsule endoscopy-based Lewis score was calculated. Associations between diffusion weighted imaging, apparent diffusion coefficient, Lewis score, and inflammatory biomarkers were evaluated. RESULTS: The study included 51 patients, and 27/51 (52.9%) with video capsule endoscopies showed jejunal mucosal inflammation. Sensitivity and specificity of restricted diffusion for video capsule endoscopy mucosal inflammation were 59.3% and 37.5% for the first reader, and 66.7% and 37.5% for the second reader, respectively. Diffusion weighted imaging was not statistically associated with jejunal video capsule endoscopy inflammation (P = 0.813). CONCLUSIONS: Diffusion weighted imaging was not an effective test for evaluation of jejunal inflammation as seen by video capsule endoscopy in patients with quiescent Crohn's disease.

Middle small-bowel segment Lewis score may predict long-term outcomes among patients with quiescent Crohn's disease.

Background: Video capsule endoscopy (VCE) has been proven to accurately diagnose small-bowel inflammation and predict flares among patients with quiescent Crohn's disease (CD). However, data regarding its predictive role in this population over an extended follow-up are scarce. Objectives: To predict clinical exacerbation and to assess the yield of Lewis score in identifying CD patients with future clinical exacerbation during an extended follow-up (>24 months). Design: A post hoc analysis study. Methods: Adult patients with quiescent small-bowel CD who were followed with VCE, inflammatory biomarkers and magnetic resonance enterography in a prospective study (between 2013 and 2018). We extracted extended clinical data (up to April 2022). The primary composite outcome (i.e. clinical exacerbation) was defined as intestinal surgery, endoscopic dilation, CD-related admission, corticosteroid administration, or biological/immunomodulator treatment change during follow-up. Results: Of the 61 patients in the study [median age 29 (24-37) years, male 57.4%, biologic treatment 46.7%], 18 patients met the primary outcome during an extended follow-up [median 58.0 (34.5-93.0) months]. On univariable analysis, complicated [hazard ratio (HR) 7.348, p = 0.002] and stricturing disease phenotype (HR 5.305, p = 0.001) were associated with higher risk for clinical exacerbation during follow-up. A baseline VCE middle small-bowel segment Lewis score (midLS) ⩾ 135 identified patients with future exacerbation [AUC (area under the curve) 0.767, 95% confidence interval (CI) 0.633-0.902, p = 0.001, HR 6.317, 93% negative predictive value], whereas the AUC of the conventional Lewis score was 0.734 (95% CI: 0.589-0.879, p = 0.004). Sensitivity analysis restricted to patients with either complicated (n = 34) or stricturing (n = 26) disease phenotype revealed that midLS still predicted clinical exacerbation during follow-up (AUC 0.747/0.753, respectively), in these patients. Conclusion: MidLS predicts treatment failure in quiescent CD patients (median follow-up of 5 years) independently of disease phenotype.

Serum matrix metalloproteinase-7: a potential biomarker in patients with Lynch Syndrome.

BACKGROUND AND AIMS: The expression of tissue and serum matrix metalloproteinase-7 (MMP-7) was shown to be elevated both in colon cancer and dysplastic lesions. We aimed to evaluate, for the first time, its role as a diagnostic marker in Lynch syndrome (LS) carriers, a hereditary syndrome with predisposition to colon cancer. METHODS: This was a case control study. Baseline serum MMP-7 levels were determined by ELISA in 40 colon cancer patients, 62 LS-carriers and 60 healthy controls. Retrieved data from medical files included demographics, background diseases, clinical data regarding tumor characteristics and genetic data. We assessed the association of serum MMP-7 levels with different variables in the study cohort using linear regression model adjusted for potential confounders. RESULTS: In crude analysis, serum MMP-7 levels were significantly higher in colon cancer group compared to LS-carriers and controls [median (IQR) 4.1 ng/ml (2.7-6.0), 2.3 ng/ml (1.7-3.1), 2.5 ng/ml (1.5-3.7), respectively; p value - p < 0.001) while there was no difference between the two last groups (p value = 0.583). However, after adjusting for age and gender, LS-carriers' patients had 18% higher concentrations of serum MMP-7 compared to healthy controls (p value = 0.037), while colon cancer patients had 50% higher serum MMP-7 level in comparison to healthy controls (p value < 0.001). Additionally, age was positively associated with higher serum MMP-7 levels across all study groups (r = 0.67, p value < 0.001). In contrast, no correlation was observed between serum MMP-7 and either tumor staging and gene mutation. CONCLUSIONS: Age-adjusted serum MMP-7 levels in asymptomatic LS carriers are higher than its levels in healthy population. While in colon cancer, MMP-7 higher level probably reflects the tumor burden and may have a prognostic effect, its significance and clinical applicability as a biomarker for tumorigenesis in LS is less clear and should be elucidated.

Patency Capsule: A Novel Independent Predictor for Long-Term Outcomes Among Patients With Quiescent Crohn's Disease.

INTRODUCTION: Patency capsule (PC) is a recommended procedure to rule out small bowel stenosis before video capsule endoscopy (VCE). We examined future clinical outcomes among patients with a failed PC vs patients in whom the PC had passed (passed PC). METHODS: A post hoc analysis of 2 prospective cohort studies of adult patients with quiescent small bowel Crohn's disease (CD) who underwent PC between 2013 and 2020. The primary composite outcome was the need for intestinal surgery or endoscopic dilation during follow-up in patients with or without a failed PC. RESULTS: A total of 190 patients were included (47: failed PC and 143: passed PC, median follow-up 34.12 months). Patients with a failed PC had higher rates of the primary composite outcome (21.3% vs 1.4%, hazard ratio [HR] 20.3, 95% confidence interval [CI] 4.4-93.7, P < 0.001) and also secondary outcomes including intestinal surgery (14.9% vs 0.70%, P < 0.001), endoscopic dilation (14.9% vs 0.70%, P < 0.001), admissions (23.3% vs 5.7%, P < 0.001), and clinical flares (43.9% vs 27.7%, P = 0.005) during follow-up compared with controls. Failed PC was the only statistically significant factor for surgery and/or endoscopic dilation, regardless of a B2/B3 phenotype at baseline. In sensitivity analyses restricted only to patients with a stricturing phenotype (n = 73), a failed PC still predicted the long-term composite outcome (HR 8.68, 95% CI 1.72-43.68, P = 0.002). Of the 190 patients ingesting a PC, only 1 patient with a failed PC had 48 hours of self-limiting mild symptoms. DISCUSSION: Patients with clinically stable CD with a failed PC have worse long-term clinical outcomes than those without, independently of the CD phenotype. Standalone PC may serve as a novel, safe, and affordable prognostic examination to identify patients with quiescent CD who have a higher risk for future worse clinical outcomes.

Risk factors and prediction algorithm for advanced neoplasia on screening colonoscopy for average-risk individuals.

Background: Screening with colonoscopy for all average-risk population is probably not cost-effective due to the limited sources and over-generalization of the risk, and risk stratification can be used to optimize colorectal cancer screening. Objectives: We aimed to assess risk factors for advanced neoplasia (AN) and a classification tree algorithm to predict the risk. Design: This is a retrospective cross-sectional study. Methods: This study was composed of consecutive asymptomatic average-risk individuals undergoing first screening colonoscopy between 2008 and 2019. Detailed characteristics including background diseases, habits, and medications were collected. We used multivariable logistic regression to investigate the associations between clinical variables and the presence of AN and built a classification algorithm to predict AN. Results: A total of 3856 patients were included (73.2% male, median age 55). Adenoma and AN detection rate were 15.8% and 3.4%, respectively. On multivariable analysis, predictors of AN [odds ratio (OR), 95% confidence interval (CI)] were age (1.04, 1.01-1.06, p = 0.003), male sex (2.69, 1.56-4.64, p < 0.001), and smoking (1.97, 1.38-2.81, p < 0.001). A classification tree algorithm showed that smoking was the most important risk factor for prediction of AN (4.9% versus 2.4%, p < 0.001), followed by age with a cutoff value of 60 in the smokers (8.4% versus 3.8%, p = 0.001) and 50 in the non-smokers (2.9% versus 0.9%, p = 0.004). Conclusion: Smoking habits, old age, and male gender are highly associated with an increased risk for AN and should be incorporated in the individualized risk-assessment to adapt a screening program.

Serum Syndecan-1: A Novel Biomarker for Pancreatic Ductal Adenocarcinoma.

INTRODUCTION: Syndecan-1 (SDC1) has multiple functions in tumorigenesis in general and specifically in pancreatic cancer. We aimed to evaluate SDC1 as a diagnostic and prognostic biomarker in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: In this case-control study, patients newly diagnosed with a biopsy-proven PDAC were enrolled alongside healthy individuals in a derivation-validation cohort design. Serum SDC1 was measured by enzyme-linked immunoassay. The diagnostic accuracy of SDC1 levels for diagnosing PDAC was computed. A unified cohort enriched with additional early-stage patients with PDAC was used to evaluate the association of SDC1 with survival outcomes and patient characteristics. RESULTS: In the derivation cohort, serum SDC1 levels were significantly higher in patients with PDAC (n = 39) compared with healthy controls (n = 20) (40.1 ng/mL, interquartile range 29.8-95.3 vs 25.6 ng/mL, interquartile range 17.1-29.8, respectively; P < 0.001). The receiver operating characteristic analysis area under the curve was 0.847 (95% confidence interval 0.747-0.947, P < 0.001). These results were replicated in a separate age-matched validation cohort (n = 38 PDAC, n = 38 controls; area under the curve 0.844, 95% confidence interval 0.757-0.932, P < 0.001). In the combined-enriched PDAC cohort (n = 110), using a cutoff of 35 ng/mL, the median overall 5-year survival between patients below and above this cutoff was not significantly different, although a trend for better survival after 1 year was found in the lower level group (P = 0.06). There were 12 of the 110 patients with PDAC (11%) who had normal CA 19-9 in the presence of elevated SDC1. DISCUSSION: These findings suggest serum SDC1 as a promising novel biomarker for early blood-based diagnosis of pancreatic cancer.

Predictors of Immunogenicity to Infliximab among Patients with Inflammatory Bowel Disease: Does Ethnicity Matter?

BACKGROUND: Up to 60% of inflammatory bowel disease (IBD) patients treated with infliximab develop antibodies to infliximab (ATI), which are associated with low drug levels and loss of response (LOR). Hence, mapping out predictors of immunogenicity toward infliximab is essential for tailoring patient-specific therapy. Jewish Sephardi ethnicity, in addition to monotherapy, has been previously identified as a potential risk factor for ATI formation and infliximab failure. OBJECTIVES: To explore the association between Jewish sub-group ethnicity among patients with IBD and the risk of infliximab immunogenicity and therapy failure. To confirm findings of a previous cohort that addressed the same question. METHODS: This retrospective cohort study included all infliximab-treated patients of Jewish ethnicity with regular prospective measurements of infliximab trough levels and ATI. Drug and ATI levels were prospectively measured, clinical data was retrieved from medical charts. RESULTS: The study comprised 109 Jewish patients (54 Ashkenazi, 55 Sephardi) treated with infliximab. There was no statistically significant difference in proportion of ATI between Sephardi and Ashkenazi patients with IBD (32% Ashkenazi and 33% Sephardi patients developed ATI, odds ratio [OR] 0.944, P = 0.9). Of all variables explored, monotherapy and older age were the only factors associated with ATI formation (OR 0.336, 95% confidence interval 0.145-0.778, P = 0.01, median 34 vs. 28, interquartile range 28-48, 23-35 years, P = 0.02, respectively). CONCLUSIONS: Contrary to previous findings, Sephardi Jewish ethnicity was not identified as a risk factor for ATI formation compared with Ashkenazi Jewish ethnicity. Other risk factors remained unchanged.

A novel PillCam Crohn's capsule score (Eliakim score) for quantification of mucosal inflammation in Crohn's disease.

INTRODUCTION: Capsule endoscopy is an important modality for monitoring of Crohn's disease. Recently, a novel panenteric capsule, PillCam Crohn's (Medtronic, USA), was approved for use. No quantitative index of inflammation for this method is currently available. This sub-study of a prospective randomized controlled Comprehensive individUalized pRoactive ThErapy of Crohn's Disease trial (CURE-CD) which aimed to compare the correlation and reliability of the novel PillCam Crohn's score with the existing small bowel capsule Lewis inflammatory score. METHODS: The study cohort included Crohn's disease patients in remission who were evaluated with PillCam Crohn's. Each result was independently reviewed by two experienced readers. Inflammation was scored in all studies using Lewis inflammatory score and PillCam Crohn's score (comprised of a sum of scores for most common and most severe lesions multiplied by percentage of segmental involvement + stricture score). RESULTS: Fifty-four PillCam Crohn's studies from 41 patients were included. The median Lewis inflammatory score was 225 for both readers. The median PillCam Crohn's score was six (0-14) and four (3-15) for readers 1 and 2, respectively. There was a high inter-rater reliability coefficient between the two readers for Lewis inflammatory and PillCam Crohn's score (0.9, p < 0.0001 for both). The correlation between PillCam Crohn's score and fecal calprotectin was stronger than for Lewis inflammatory score (r = 0.32 and 0.54 respectively, p = 0.001 for both). CONCLUSIONS: The novel panenteric capsule score correlates well with the Lewis inflammatory score, has excellent reliability, and may be potentially more accurate in estimation of the panenteric inflammatory burden.

Risk of metachronous neoplasia on surveillance colonoscopy among young and older patients after polypectomy.

BACKGROUND AND AIMS: Few reports address the appropriate colonoscopy surveillance interval for individuals <50-years-old. We compared the risk of metachronous neoplasia among young (<50 years), adult (50-74 years) and older (≥75 y) age groups. METHODS: This was a single center retrospective cohort study. Eligible subjects underwent their first colonoscopy with polypectomy between 2005 and 2014 and had at least one surveillance colonoscopy 3-5 years later. Patients (N = 495) were stratified at baseline into low-risk adenoma (LRA) and advanced adenoma groups. Study outcomes were overall and high-risk neoplasia at surveillance colonoscopy. RESULTS: In the baseline LRA-group (N = 201), the 5-year risk of metachronous high-risk neoplasia was 12.5%, 15.2% and 22.5% (P = 0.426) in the young, adult and older age groups, respectively. In the baseline advanced adenoma group (N = 294), the 3-year risk of metachronous high-risk neoplasia was 13.3%, 14.8% and 25.3% (P = 0.041), respectively. In multivariate analysis, the only risk factor for metachronous high-risk neoplasia was older age (OR 1.876, CI 1.087-3.238; P = 0.024). CONCLUSIONS: Considering the comparable risk of metachronous high-risk neoplasia in young and adult patients, surveillance recommendations after polypectomy should not differ. Since this risk is higher among older people, more frequent surveillance schedule can be considered for this age group but should be individualized.

Serum MMP-9: a novel biomarker for prediction of clinical relapse in patients with quiescent Crohn's disease, a post hoc analysis.

BACKGROUND: Matrix metalloproteinase-9 (MMP-9) is a novel marker of intestinal inflammation. The aim of this study was to assess if serum MMP-9 levels predict clinical flare in patients with quiescent Crohn's disease (CD). METHODS: This study was a post hoc analysis of a prospective observational study in which quiescent CD patients were included and followed until clinical relapse or the end of a 2-year follow-up period. Serial C-reactive protein (CRP) and fecal calprotectin (FC) levels were measured, and the patients underwent repeated capsule endoscopies (CEs) every 6 months. Small bowel inflammation was quantified by Lewis score (LS) for CE. A baseline magnetic resonance enterography was also performed, and MaRIA score was calculated. Serum MMP-9 levels in baseline blood samples were quantified by ELISA. RESULTS: Out of 58 eligible enrolled patients, 16 had a flare. Higher levels of baseline MMP-9 were found in patients who developed subsequent symptomatic flare compared with patients who did not [median 661 ng/ml, 25-75 interquartile range (IQR; 478.2-1441.3) versus 525.5 ng/ ml (339-662.7), respectively, p = 0.01]. Patients with serum MMP-9 levels of 945 ng/ ml or higher were at increased risk for relapse within 24 months [area under the curve (AUC) of 0.72 [95% confidence interval (CI): 0.56-0.88]; hazard ratio 8.1 (95% CI 3.0-21.9, p < 0.001)]. Serum MMP-9 concentrations showed weak and moderate correlation to baseline LS and FC, respectively (r = 0.31, p = 0.02; r = 0.46, p < 0.001). No correlation was found between serum MMP-9 to CRP and MaRIA score. CONCLUSIONS: Serum MMP-9 may be a promising biomarker for prediction of clinical flare in CD patients with quiescent disease.

Assessment of small bowel mucosal healing by video capsule endoscopy for the prediction of short-term and long-term risk of Crohn's disease flare: a prospective cohort study.

BACKGROUND: The optimal monitoring strategy for predicting disease course in Crohn's disease remains undefined. We aimed to evaluate the accuracy, safety, and tolerability of an intensive monitoring strategy designed to predict the future course of Crohn's disease in patients with quiescent disease. METHODS: In a prospective observational cohort study, we recruited patients older than 18 years with quiescent (for 3-24 months) Crohn's disease involving the small bowel with confirmed small bowel patency from three tertiary medical centres in Israel. Enrolled patients underwent baseline magnetic resonance enterography (MRE) and patency capsule, clinical or biomarker assessment every 3 months, and video capsule endoscopy (VCE) at baseline and every 6 months for 2 years or until a clinical flare (the primary outcome, defined as an increase in the Crohn's disease activity index score by 70 points or more) or disease worsening necessitating treatment intensification. We assessed the ability of the different Crohn's disease monitoring methods used to predict the occurrence of a flare during the 24-month follow-up period. FINDINGS: Of 90 screened patients, 29 were excluded (17 because of non-patent small bowel). Of the 61 patients enrolled between July 3, 2013, and Feb 1, 2015, 17 (28%) had a flare during the 24-month follow-up. No clinicodemographic parameter predicted future flare. A baseline VCE Lewis score of 350 or more identified patients with future flare (area under the curve [AUC] 0·79, 95% CI 0·66-0·88; p<0·0001; hazard ratio 10·7, 3·8-30·3). C-reactive protein at baseline had an AUC of 0·73 (0·6-0·84; p=0·0013) for predicting flare. The AUC of baseline faecal calprotectin for the prediction of flare occurring within 2 years was 0·62 (0·49-0·74; p=0·17), but progressively improved for shorter timespans and reached an AUC of 0·81 (0·76-0·85) for the prediction of flare occurring within 3 months. Of four MRE-based indices, only MRE global score correlated with 2-year flare risk (AUC 0·71, 0·58-0·82; p=0·024). During follow-up, a Lewis score increase of 383 points or more from baseline predicted imminent disease exacerbation within 6 months (AUC 0·79, 0·65-0·89; p=0·011). The safety and tolerability of the 231 VCEs ingested was excellent, with none being retained. INTERPRETATION: In patients with quiescent Crohn's disease involving the small bowel, faecal calprotectin predicts short-term flare risk, whereas VCE predicts both short-term and long-term risk of disease exacerbation. If corroborated by additional studies, protocols incorporating VCE could expand the scope of available methods for monitoring disease activity and predicting outcomes in small bowel Crohn's disease. FUNDING: The Leona M & Harry B Helmsley Charitable Trust.

Individualized Dynamics in the Gut Microbiota Precede Crohn's Disease Flares.

OBJECTIVES: Crohn's disease (CD) is a chronic relapsing-remitting gut inflammatory disorder with a heterogeneous unpredictable course. Dysbiosis occurs in CD; however, whether microbial dynamics in quiescent CD are instrumental in increasing the risk of a subsequent flare remains undefined. METHODS: We analyzed the long-term dynamics of microbial composition in a prospective observational cohort of patients with quiescent CD (45 cases, 217 samples) over 2 years or until clinical flare occurred, aiming to identify whether changes in the microbiome precede and predict clinical relapse. Machine learning was used to prioritize microbial and clinical factors that discriminate between relapsers and nonrelapsers in the quiescent phase. RESULTS: Patients with CD in clinical, biomarker, and mucosal remission showed significantly reduced microbial richness and increased dysbiosis index compared with healthy controls. Of the 45 patients with quiescent CD, 12 (27%) flared during follow-up. Samples in quiescent patients preceding flare showed significantly reduced abundance of Christensenellaceae and S24.7, and increased abundance of Gemellaceae compared with those in remission throughout. A composite flare index was associated with a subsequent flare. Notably, higher individualized microbial instability in the quiescent phase was associated with a higher risk of a subsequent flare (hazard ratio 11.32, 95% confidence interval 3-42, P = 0.0035) using two preflare samples. Importantly, machine learning prioritized the flare index and the intrapersonal instability over clinical factors to best discriminate between relapsers and nonrelapsers. DISCUSSION: Individualized microbial variations in quiescent CD significantly increase the risk of future exacerbation and may provide a model to guide personalized preemptive therapy intensification.

Prospective Observational Evaluation of Time-Dependency of Adalimumab Immunogenicity and Drug Concentrations: The POETIC Study.

OBJECTIVES: Adalimumab is usually self-injected at home, making prospective serial-sampling studies challenging and scarce. This has led to a gap in knowledge about evolution of anti-adalimumab antibodies (AAAs) over time and its correlation with clinical and inflammatory outcomes. METHODS: A program for home visits by physicians at induction, every 3 months and at event of relapse, was established prospectively for Crohn's disease (CD) patients. At each visit, patients' clinical scores were determined and sera were obtained for C-reactive protein, drug, and AAA levels. This cohort was compared to a parallel prospective cohort of infliximab-treated CD patients. In a subgroup of 29 patients, trough and in-between-trough levels were compared, to elucidate the importance of timing of sampling during the injection cycle. RESULTS: Ninety-eight CD patients starting adalimumab were prospectively followed (median follow-up 44 weeks) and 621 serum samples were analyzed. Thirty-three patients (32%) developed AAA; 18/33 (55%) of them as early as week 2, and 26/33 (79%) by week 14. Induction period AAAs were strongly associated with primary non-response (odds ratio (OR) = 5.4, 95% confidence interval (CI): 1.6-17.8, p = 0.005). As compared to antibodies-to-infliximab (ATI), AAA formation rate over time was significantly lower (p = 0.01) and AAA were much more specific-85% of AAA events were associated with loss-of-response compared with 58% rate for ATI (p = 0.01). In 29 patients sampled serially during an injection cycle, levels of drug and AAA seemed comparable between four time-points during a single cycle both in patients with or without AAA (n = 8, n = 21, respectively). CONCLUSIONS: When followed prospectively and serially, AAAs are found to arise earlier than previously appreciated and their impact may be more pronounced for primary rather than secondary, non-response. Drug and AAA levels were similar both at trough and in-between injections, enabling to simplify therapeutic drug monitoring of adalimumab.

The Lewis score or the capsule endoscopy Crohn's disease activity index: which one is better for the assessment of small bowel inflammation in established Crohn's disease?

BACKGROUND: Small-bowel capsule endoscopy (CE) is a prime modality for evaluation of the small bowel. The Lewis score (LS) and the Capsule Endoscopy Crohn's Disease Activity Index (CECDAI) are validated endoscopic indices for quantification of small-bowel inflammation on CE. It is unclear whether these indexes are interchangeable for the evaluation of mucosal inflammation in established Crohn's disease (CD). The aim of this study was to compare the quantitative evaluation of small- bowel inflammation by LS and CECDAI. METHODS: Patients with known quiescent small-bowel CD for at least 3 months (Crohn's disease activity index < 150) were prospectively recruited and underwent CE. The LS was calculated using RAPID 8 capsule-reading software and the CECDAI was calculated manually. Cumulative LS (C-LS) was calculated by summation of individual tertile LS. Fecal calprotectin (FCP) and C-reactive protein (CRP) levels were measured and correlated with the scores. RESULTS: A total of 50 patients were included in the study. There was a moderate correlation between the worst segment LS and CECDAI (Pearson's r = 0.66, p = 0.001), and a strong correlation between C-LS and CECDAI (r = 0.81, p = 0.0001). CECDAI < 5.4 corresponded to mucosal healing (LS < 135), while CECDAI > 9.2 corresponded to moderate-to-severe inflammation (LS ⩾ 790). There was a moderate correlation between capsule scores and FCP levels (r = 0.39, p = 0.002 for LS, r = 0.48, p = 0.001 for C-LS, and r = 0.53, p = 0.001 for CECDAI, respectively). CRP levels were not significantly correlated with either score. CONCLUSIONS: CECDAI and C-LS are strongly correlated and perform similarly for quantitative assessment of mucosal inflammation in established CD.

Capsule Endoscopy Validation of the Magnetic Enterography Global Score in Patients with Established Crohn's Disease.

BACKGROUND AND AIMS: Capsule endoscopy [CE] and magnetic resonance enterography [MRE] are prime modalities for evaluation of the small bowel in Crohn's disease [CD]. Detection of proximal small bowel [SB] inflammation in CD by MRE is challenging. Currently available quantitative MRE scores do not incorporate proximal SB data. The MRE global score [MEGS] was designed for quantitative evaluation of the entire digestive tract; its accuracy in the proximal SB has not previously been evaluated. This study compared the evaluation of the small bowel inflammation by MEGS and CE-derived quantitative score (the Lewis score[LS]). METHODS: CD patients in stable clinical remission were prospectively recruited and underwent MRE and CE; faecal calprotectin [FC] levels were obtained. MEGS was calculated for each SB segment and the entire SB [SBMEGS]. SB inflammation on CE was quantified using LS. A cumulative Lewis score [C-LS] was calculated based on summation of three tertiles scores. RESULTS: Fifty patients were included. There was a significant correlation of SBMEGS with LS and C-LS [r = 0.61 and 0.71, both p = 0.001]. The correlation with FC was stronger for MEGS than for LS or C-LS [r = 0.68 vs r = 0.46 vs r = 0.53, all p = 0.001]. The correlation between the proximal LS and MEGS was significant [r = 0.55, p = 0.001]; median MEGS was significantly different in patients, with LS values consistent with mucosal healing, mild and moderate-to-severe inflammation. CONCLUSIONS: MEGS provides accurate evaluation of the SB and strongly correlates with FC; the main advantage of MEGS is the accurate quantification of proximal SB inflammation unavailable for alternative MRE scores.

Assessment of patency capsule retention using MR diffusion-weighted imaging.

OBJECTIVES: Evaluate the ability of MR diffusion-weighted imaging (DWI) to predict patency capsule retention in Crohn's disease (CD). METHODS: Clinical and imaging data were prospectively reviewed for 80 CD patients following patency capsule administration and MR-DWI under institutional review board (IRB) approval with informed consent. Two radiologists separately assessed the presence/absence of restricted diffusion in the distal ileum. Apparent diffusion coefficients (ADC) from three regions of interest on the ileal wall were averaged. The association between restricted diffusion and retention, and sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated. Ability of ADC to predict retention was assessed with receiver operating characteristic (ROC) curve analysis. RESULTS: Restricted diffusion in the distal ileum was associated with capsule retention (p = 0.001, p < 0.0001). Sensitivity, specificity, PPV and NPV of restricted diffusion for capsule retention were 100.0%, 46.2%, 30.0%, 100% and 100.0%, 56.9%, 34.9%, 100%, respectively, for two radiologists. Accuracy of ADC to predict retention was high (area under the curve = 0.851, p < 0.0001). An ADC of 1.47 mm2/s showed 90.0% sensitivity and 50.0% specificity for retention. CONCLUSIONS: Sensitivity and NPV of restricted diffusion for patency capsule retention were 100%, suggesting that DWI may predict gastrointestinal tract capability to pass video camera endoscopy. KEY POINTS: • Capsule endoscopy enables assessment of the gastrointestinal mucosa in Crohn's disease • Prior patency capsule administration is recommended to evaluate gastrointestinal tract patency • MR diffusion-weighted imaging may detect pathological constriction of the ileum • Restricted diffusion in the distal ileum was associated with capsule retention • MR-DWI may predict gastrointestinal tract capability to pass capsule endoscopy.

Helicobacter pylori prevalence and clinical significance in patients with quiescent Crohn's disease.

BACKGROUND: Helicobacter pylori (HP) infection is present in about 50% of the global population, and is associated with chronic gastritis, peptic disease and gastric malignancies. HP prevalence in Crohn's disease (CD) patients was shown to be low compared to the general population, and its influence on disease activity is yet to be determined. Our aims were to determine the prevalence of HP in a selected group of CD patients with quiescent disease, and to assess the influence of its eradication on disease activity and endoscopic and laboratory activity measures. METHODS: Consecutive CD patients with quiescent disease underwent meticulous disease evaluation with MR enterography (MRE), video capsule endoscopy (VCE), CRP, fecal calprotectin and CDAI. All patients were tested for the presence of HP using stool antigen detection kit. Patients infected with HP were offered eradication treatment with sequential therapy. HP eradication was confirmed using urease breath test and stool antigen test. The influence of HP eradication on disease activity was assessed. RESULTS: Out of 56 patients enrolled, six patients (10.7%) had HP infection. Of them, five patients had gastro- duodenitis per VCE. All HP positive patients were offered eradication treatment and underwent successful eradication. Notably, 23 (50%) of patients had proximal disease per VCE, most of them (78%) were HP negative. CDAI, CRP, fecal calprotectin and VCE Lewis inflammatory score did not change significantly following HP eradication, Gastric findings on VCE were not impacted by HP eradication. CONCLUSIONS: The prevalence of HP infection in patients with quiescent CD is relatively low. Eradication of the bacteria did not significantly change neither disease activity measures nor the presence of gastro- duodenitis per VCE, suggesting it might be part of proximal CD. The influence of HP on CD activity merits further investigation.

Structural bowel damage in quiescent Crohn's disease.

BACKGROUND: Crohn's disease is associated with accumulation of progressive structural bowel damage (SBD) leading to the development of stenotic and penetrating complications. The data pertaining to the course of progression of SBD is scarce. The Lemann index (LI) is a novel tool for evaluation of SBD that incorporates pan-enteric clinical, endoscopic and imaging data. AIMS: To evaluate the progression of SBD in quiescent CD patients. METHODS: Patients with known quiescent small bowel Crohn's disease (CD) for at least 3 months (CDAI<220) were prospectively recruited and underwent repeated magnetic resonance enterographies (MRE) and video capsule endoscopies (VCE). Patients were assessed for SBD on initial and follow-up evaluation using relevant clinicopathological data, MRE and VCE results. Significant structural bowel damage (SBD) was identified as LI>4.8, and progression of SBD as LI>0.3. RESULTS: Sixty one patients were enrolled in the study. Significant SBD was detected 13 (21.4%) on enrollment. Duration of disease (p=0.036) and history of CD-related surgery (p=0.0001) were associated with significant BD. Forty one patients underwent a follow-up MRE (14.8±2.5 months apart). LI was similar at baseline and follow-up. There was a negligible change in LI between the evaluations. CONCLUSIONS: In patients with quiescent Crohn's disease, structural bowel damage was stable over a median of 14 months follow-up.

Magnetic resonance enterography versus capsule endoscopy activity indices for quantification of small bowel inflammation in Crohn's disease.

BACKGROUND: Video capsule endoscopy (VCE) and magnetic resonance enterography (MRE) are the prime modalities for the evaluation of small bowel (SB) Crohn's disease (CD). Mucosal inflammation on VCE is quantified using the Lewis score (LS). Diffusion-weighted (DW) magnetic resonance imaging (MRI) allows for accurate assessment of SB inflammation without administration of intravenous contrast material. The Magnetic Resonance Index of Activity (MaRiA) and the Clermont index are quantitative activity indices validated for contrast-enhanced MRE and DW-MRE, respectively. The aim of this study was to compare the quantification of distal SB inflammation by VCE and MR-related activity indices. METHODS: Patients with known quiescent SB CD were prospectively recruited and underwent MRE and VCE. LS, MaRIA and Clermont scores were calculated for the distal SB. RESULTS: Both MRI-based indices significantly correlated with the LS and the Clermont index (r = 0.50, p = 0.001 and r = 0.53, p = 0.001, respectively). Both MaRIA and Clermont scores were significantly lower in patients with mucosal healing (LS < 135). The area under the curve (AUC) with both MR scores was moderate for prediction of any mucosal inflammation (LS ⩾ 135) and excellent for prediction of moderate-to-severe inflammation (LS ⩾ 790) (0.71 and 0.74 versus 0.93 and 0.91 for MaRIA and Clermont score, respectively). CONCLUSIONS: Modest correlation between VCE- and MRE-based quantitative indices of inflammation in patients with quiescent SB CD was observed. Between-modality correlation was higher in patients with endoscopically severe disease. DW-MRE gauged by Clermont score was at least as accurate as contrast-enhanced MRE for quantification of SB inflammation.