Gut-associated lymphoid tissue attrition associates with response to anti-α4ß7 therapy in ulcerative colitis.

Targeting the α4ß7-MAdCAM-1 axis with vedolizumab (VDZ) is a front-line therapeutic paradigm in ulcerative colitis (UC). However, mechanism(s) of action (MOA) of VDZ remain relatively undefined. Here, we examined three distinct cohorts of patients with UC (n=83, n=60, and n=21), to determine the effect of VDZ on the mucosal and peripheral immune system. Transcriptomic studies with protein level validation were used to study drug MOA using conventional and transgenic murine models. We found a significant decrease in colonic and ileal naïve B and T cells and circulating gut-homing plasmablasts (ß7+) in VDZ-treated patients, pointing to gut-associated lymphoid tissue (GALT) targeting by VDZ. Murine Peyer's patches (PP) demonstrated a significant loss cellularity associated with reduction in follicular B cells, including a unique population of epithelium-associated B cells, following anti-α4ß7 antibody (mAb) administration. Photoconvertible (KikGR) mice unequivocally demonstrated impaired cellular entry into PPs in anti-α4ß7 mAb treated mice. In VDZ-treated, but not anti-tumor necrosis factor-treated UC patients, lymphoid aggregate size was significantly reduced in treatment responders compared to non-responders, with an independent validation cohort further confirming these data. GALT targeting represents a novel MOA of α4ß7-targeted therapies, with major implications for this therapeutic paradigm in UC, and for the development of new therapeutic strategies.

Current Trends in IBD-Development of Mucosal-Based Biomarkers and a Novel Minimally Invasive Recoverable Sampling System.

Despite recent developments in therapy for inflammatory bowel diseases (IBDs), there have been limited advances in diagnostic tools available to aid in disease management. A growing body of evidence suggests that there are important host-microbe interactions at the mucosal interface that modulate the inflammatory response in patients with IBD. Additionally, the importance of mucosal integrity and its disruption appears to be important in the pathophysiology and perpetuation of the disease. The ability to characterize this interface may provide valuable information for both disease monitoring and identification of new treatment targets. Endoscopy remains the primary tool for disease monitoring, and mucosal healing is the primary therapeutic target in IBD treatment. However, establishing mucosal healing requires repetitive endoscopic procedures, and endoscopy is limited by factors such as invasiveness, cost, and risk of adverse events. Moreover, the use of a bowel preparation for colonoscopies alters the mucus layer and thus perturbs evaluation of the host-microbe interaction. Stool sampling may also be inaccurate because it reflects the end state of metabolites and proteins, failing to take into account the degradation or alteration of substrates of interest by bacterial proteases and other enzymes during passage through the colon. A novel sampling capsule, called the Recoverable Sampling System (RSS), is being developed as a complementary tool to colonoscopy. The RSS is intended to be a platform for noninvasive autonomous sampling, preservation, handling, and storage of analytes of interest found in the gastrointestinal fluids. A proprietary preservative contained within the chambers of the capsule has been developed to stabilize DNA and proteins for ex vivo microbiome and metabolomics analyses. Surrogate markers such as SPP24 and GUCA2a have been identified to correlate with gut health, intestinal permeability, and inflammation and could be locally sampled by the RSS. The potential clinical utility of an RSS device is broad and would likely be able to guide therapy by allowing for more frequent disease monitoring, aiding in disease characterization, and facilitating in the identification of novel therapeutic targets.

A new technology is being developed, Recoverable Sampling System (RSS), that may allow sampling without a colonoscopy. This may lead to new biomarkers and even drug targets which may ultimately improve the care of these patients.

Blockage of bacterial FimH prevents mucosal inflammation associated with Crohn's disease.

BACKGROUND: An Escherichia coli (E. coli) pathotype with invasive properties, first reported by Darfeuille-Michaud and termed adherent-invasive E. coli (AIEC), was shown to be prevalent in up to half the individuals with Crohn's Disease (CD), suggesting that these bacteria could be involved in the pathophysiology of CD. Among the genes related to AIEC pathogenicity, fim has the potential to generate an inflammatory reaction from the intestinal epithelial cells and macrophages, as it interacts with TLR4, inducing the production of inflammatory cytokines independently of LPS. Therefore, targeting the bacterial adhesion of FimH-expressing bacteria seems a promising therapeutic approach, consisting of disarming bacteria without killing them, representing a selective strategy to suppress a potentially critical trigger of intestinal inflammation, without disturbing the intestinal microbiota. RESULTS: We analyzed the metagenomic composition of the gut microbiome of 358 patients with CD from two different cohorts and characterized the presence of FimH-expressing bacteria. To assess the pathogenic role of FimH, we used human intestinal explants and tested a specific FimH blocker to prevent bacterial adhesion and associated inflammation. We observed a significant and disease activity-dependent enrichment of Enterobacteriaceae in the gut microbiome of patients with CD. Bacterial FimH expression was functionally confirmed in ileal biopsies from 65% of the patients with CD. Using human intestinal explants, we further show that FimH is essential for adhesion and to trigger inflammation. Finally, a specific FimH-blocker, TAK-018, inhibits bacterial adhesion to the intestinal epithelium and prevents inflammation, thus preserving mucosal integrity. CONCLUSIONS: We propose that TAK-018, which is safe and well tolerated in humans, is a promising candidate for the treatment of CD and in particular in preventing its recurrence. Video abstract.

Novel Associations Between Genome-Wide Single Nucleotide Polymorphisms and MR Enterography Features in Crohn's Disease Patients.

BACKGROUND: Patient genetic polymorphism is associated with Crohn's clinical behavior; however, its association with magnetic resonance enterography (MRE) imaging appearance is not known. PURPOSE: To analyze a set of known Crohn's disease (CD)-related single nucleotide polymorphisms for associations with MRE imaging phenotype and frequency of imaging. STUDY TYPE: Retrospective. POPULATION: 54 patients (mean age 40 years; 32 females and 22 males) with established CD from 2009 to 2016 who underwent baseline MRE and genetic testing for the presence of 168 single nucleotide polymorphisms (SNPs) potentially associated with inflammatory bowel disease. FIELD STRENGTH/SEQUENCE: 1.5T or 3T clinical scanners, standard MRE clinical pulse sequences, including T2 -weighted single-shot fast spin echo, balanced steady-state free precession, T2 -weighted fast spin echo fat-suppressed, and T1 -weighted fat-suppressed pre- and postcontrast imaging. ASSESSMENT: Three readers (all body imaging fellowship-trained radiologists) independently evaluated all imaging for the presence or absence of active disease and penetrating complications. Date of onset and frequency of endoscopies and cross-sectional imaging (CSI) were recorded. Disease behavior and distribution were categorized according to the Vienna and Montreal classifications, respectively. STATISTICAL TESTS: Student's t-test and Fisher's exact test were used to assess significance of continuous and categorical variables, respectively. A hidden Markov model statistical knockoff approach was also applied for the analysis of genetic-imaging associations, with corrected P < 0.05 considered significant. RESULTS: MRE demonstrated active bowel inflammation in 42 (78%) patients, strictures in 13 (28%), and fistulae in 13 (28%). The SNP rs1292053 (RBS6KB1) was highly associated with small bowel inflammation and luminal narrowing, with observed frequencies of association 0.66 and 0.39, respectively (P = 0.001). rs6062504 (Decoy receptor 3) was associated with lower age of onset (P = 0.012), higher proportion of early disease onset patients (P = 0.012), and higher average number of CSI/year (P = 0.014). DATA CONCLUSION: This study demonstrated significant associations between CD genotype and MRE phenotype and frequency of cross-sectional imaging. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.

Hormone Therapy for Cancer Is a Risk Factor for Relapse of Inflammatory Bowel Diseases.

BACKGROUND & AIMS: Exposure to hormone contraception has been associated with an increased risk of relapse of inflammatory bowel diseases (IBDs). Little is known about the effects of cancer therapies, specifically hormone therapies, on the course of IBD. METHODS: We conducted a retrospective cohort study, collecting data from 5 medical centers, on patients with IBD who received a subsequent diagnosis of breast or prostate cancer from 1997 through 2018. For patients with quiescent IBD at their cancer diagnosis, the primary outcome was relapse of IBD. For patients with active IBD at their cancer diagnosis, the primary outcome was IBD remission. RESULTS: Our analysis included 447 patients with IBD (44% with Crohn's disease, 53% with ulcerative colitis, and 3% with IBD unclassified) who had either breast (78%) or prostate (22%) cancer. At their cancer diagnosis, 400 patients (90%) had inactive IBD, and 47 (10%) had active IBD. Among patients with inactive IBD, 112 (28%) developed active IBD. Previous exposure to steroids, immunomodulators, or biologics was associated with IBD relapse after a cancer diagnosis (hazard ratio [HR] for steroids, 1.79; 95% CI, 1.18-2.71; HR for immunomodulators, 2.22; 95% CI, 1.38-3.55; HR for biologics, 1.95; 95% CI, 1.01-5.36). Hormone monotherapy (HR, 2.00; 95% CI, 1.21-3.29) and combination cytotoxic and hormone therapy (HR, 1.86; 95% CI, 1.01-3.43) was associated with IBD relapse. Among 34 patients who received only cytotoxic chemotherapy, 75% remained in remission from IBD at 250 months compared with 42% of those who received hormone monotherapy (log rank, 0.02). Among patients with active IBD at their cancer diagnosis, 14 (30%) entered remission from IBD, but there were no significant factors of achieving IBD remission. CONCLUSIONS: In a multicenter retrospective study, we found that patients with IBD and breast or prostate cancer who receive hormone therapy have an increased risk for relapse of IBD and related adverse outcomes.

Challenges in IBD Research: Novel Technologies.

Novel technologies is part of five focus areas of the Challenges in IBD research document, which also includes preclinical human IBD mechanisms, environmental triggers, precision medicine and pragmatic clinical research. The Challenges in IBD research document provides a comprehensive overview of current gaps in inflammatory bowel diseases (IBD) research and delivers actionable approaches to address them. It is the result of a multidisciplinary input from scientists, clinicians, patients, and funders, and represents a valuable resource for patient centric research prioritization. In particular, the novel technologies section is focused on prioritizing unmet clinical needs in IBD that will benefit from novel technologies applied to: 1) non-invasive detection and monitoring of active inflammation and assessment of treatment response; 2) mucosal targeted drug delivery systems; and 3) prevention of post-operative septic complications and treatment of fistulizing complications. Proposed approaches include development of multiparametric imaging modalities and biosensors, to enable non invasive or minimally invasive detection of pro-inflammatory signals to monitor disease activity and treatment responses. Additionally, technologies for local drug delivery to control unremitting disease and increase treatment efficacy while decreasing systemic exposure are also proposed. Finally, research on biopolymers and other sealant technologies to promote post-surgical healing; and devices to control anastomotic leakage and prevent post-surgical complications and recurrences are also needed.

Survey on practice patterns in imaging utilization in patients with Crohn's disease.

PURPOSE: To perform a survey-based assessment of imaging practice preferences in Crohn's disease (CD). METHODS: An internet-based questionnaire was sent to physicians involved in CD care. The questionnaire addressed the experience, practice patterns, choice of modality, and recent trends in imaging utilization. RESULTS: The response rate was 7.57% (122/1598) with 43.8% of respondents involved in care of CD for ≥10 years. CT was mostly preferred by ED physicians, internists and primary care physicians, while MRI by gastroenterologists and pediatricians. Practitioners from non-teaching facilities had higher preference for CT (CT:42% andMR:27%), compared to teaching/academic hospitals (MR:45% and CT: 40%) (p = 0.06). MR was preferred by pediatric practitioners compared to physicians serving older age group of patients (>16 yrs) (p = 0.01). CT was preferred by physicians taking care of <50 patients/year (CT:37, MR:27, No preference = 19) and MR preferred by physicians serving ≥50 patients/year (CT:12, MR:21, No preference:3)(p = 0.02). CT/CT enterography was the most widely used exam (93.3%) and preferred modality for evaluation of acute CD exacerbation (87.7%), followed by assessment for new symptoms (73.7%) and extra-intestinal manifestations (61.3%). MR/MR enterography (58%) was more preferred for asymptomatic CD patients for disease surveillance. Nearly 80% of respondents reported a change in imaging preferences, 46.5% respondents indicating growing preference for MRI while 33.3% reported increasing preference for CT. 29.6% physicians reported a patient preference for MRI over CT (13%) with the most common factor for choice of MRI being fear of harmful effects of radiation (60.2%). CONCLUSION: Physician practices reported continued preference for CT in evaluation of patients with CD, particularly for evaluation of acute exacerbation, new symptoms or extra-intestinal manifestations. Physician providers with large practice volume, younger patient population and GI sub-specialty expertise report growing MRI utilization.

Integrin αM activation and upregulation on esophageal eosinophils and periostin-mediated eosinophil survival in eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is an increasingly recognized allergic disease associated with dysphagia and esophageal fibrosis. We aimed to determine expression patterns of specific eosinophil integrins that promote eosinophilic infiltration of the esophageal epithelium, and to determine how key EoE-related cytokines influence eosinophil activation and survival. Esophageal and peripheral eosinophils were isolated from 20 adult subjects with EoE for immunophenotyping and integrin profiling using multicolor flow cytometry and immunohistochemistry. Expression signatures of eosinophil integrins were further assessed by immunohistochemistry using serial sections of esophageal biopsy specimens. Purified eosinophils were used to assess the effect of EoE-relevant cytokines and recombinant periostin on expression of known eosinophil integrins and eosinophil survival and activation. We found that resting eosinophils express high levels of the ß2-pairing integrins αL and αM, and lower levels of α4, α6 and α4ß7. The migration of peripheral eosinophils to the esophagus is characterized by the specific induction of αM, and a significant increase in the proportion of αM in high-activity conformation. Periostin, a secreted extracellular matrix protein that is significantly overexpressed in EoE, enhances eosinophil survival, and this effect is mediated by αM interaction. Integrin αM is a specific marker of activated tissue eosinophils in EoE, and promotes eosinophil survival through interactions with periostin. The ability of αMß2 to mediate eosinophil tissue residency via periostin represents a key mechanism for disease development and a potential therapeutic target in EoE.

Effect of oral tobacco use and smoking on outcomes of Crohn's disease in India.

BACKGROUND AND AIM: Smoking has been linked with adverse outcomes in Crohn's disease (CD); however, it is not known whether oral tobacco (OT) use affects disease outcomes in these patients. The study aimed to assess the association between smoking or OT and outcomes in CD. METHODS: Retrospective analysis was performed on prospectively maintained records of CD patients from 2004 to 2016. The parameters assessed included disease characteristics at baseline (location, behavior, age at onset, perianal disease, and extraintestinal manifestations), course pattern, and outcomes (surgery, hospitalizations, immunomodulator or biologics use, and steroid requirement). RESULTS: A total of 426 patients were included (mean age: 39.9 years; 59.9% men; median follow up: 71 months). Forty patients were ever-OT users, and 59 were ever-smokers, ever-use being defined as daily use for at least 2 years. OT use was associated with male sex and smoking. Both OT use and smoking had no effect on baseline characteristics, but upper gastrointestinal disease was less common in ever-smokers. Both OT use and smoking did not have any effect on surgery, immunomodulator, and biologic use. Similarly, no association was found between these outcomes and duration, daily, and cumulative exposure to tobacco. Current but not former tobacco use in both smoked (adjusted odds ratio = 2.59 [1.22-5.49]) and OT (adjusted odds ratio = 2.97 [1.03-8.6]) forms increased risk of hospitalizations. CONCLUSION: Oral tobacco use and smoking had no significant detrimental effect on disease phenotype or medical and surgical requirements in CD in Indian patients, affirming other non-Caucasian studies that found lack of effect of smoking. However, current tobacco use in any form was associated with hospitalization during follow up.

Differences in Clinical Course, Genetics, and the Microbiome Between Familial and Sporadic Inflammatory Bowel Diseases.

BACKGROUND AND AIM: Family history is the strongest risk factor for developing Crohn's disease [CD] or ulcerative colitis [UC]. We investigated whether the proximity of relationship with the affected relative and concordance for type of inflammatory bowel disease [IBD] modifies the effect of family history on phenotype and disease severity. METHOD: This cross-sectional study included patients with a confirmed diagnosis of IBD in a clinical registry. Family history of IBD was assessed by a questionnaire ascertaining presence of disease in a first-first-degree, second-second-degree or distant relative. Our primary outcomes were disease phenotype as per the Montreal classification and severity measured by need for immunomodulator, biologic, or surgical therapy. Genotyping was performed on the Immunochip and faecal samples were subjected to 16S rRNA microbiome sequencing. RESULTS: Our study included 2136 patients with IBD [1197 CD, 939 UC]. Just under one-third [32%] of cases ere familial IBD [17% first-degree, 21% second-degree]. Familial IBD was diagnosed at an earlier age, both in CD [26 vs 28 years, p = 0.0006] and UC [29 vs 32 years, p = 0.01]. Among CD patients, a positive family history for CD was associated with an increased risk for complicated disease in the presence of an affected family member (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.07-2.03). However, this effect was significant only for first-degree relatives [OR 1.82, 95% CI 1.19-2.78]. CONCLUSIONS: A family history of CD in first-degree relatives was associated with complicated CD. Family history discordant for type of IBD or in distant relatives did not influence disease phenotype or natural history.

Clinical Predictors and Natural History of Disease Extension in Patients with Ulcerative Proctitis.

BACKGROUND: A proportion of patients with initial presentation of ulcerative proctitis (UP) progress to more extensive colitis. We sought to characterize the natural history and identify clinical predictors of extension in UP. METHODS: We performed a retrospective cohort study of participants with a new diagnosis of UP from January 2000 to December 2015. We used Cox proportional hazard modeling to identify predictors of disease extension. RESULTS: We identified 169 new cases of UP with a median age of diagnosis of 40 years (range: 16-91 yr) and a median follow-up of 4.3 years (range: 3.3-15.1 yr). Fifty-three (31%) patients developed extension over the follow-up time. Compared with nonextenders, the need for immunosuppressive or biologic therapy was significantly higher among extenders (34% versus 2.6%, P < 0.001). In multivariable analyses, compared with UP cases with body mass index <25, the adjusted hazard ratios of extension were 1.75 (95% confidence interval [CI], 0.95-3.23) and 2.77 (95% CI, 1.07-7.14) among overweight and obese patients, respectively (Ptrend = 0.03). Similarly, patients with a history of appendectomy or endoscopic finding of moderate to severe disease had a higher risk of extension (adjusted hazard ratio = 2.74, 95% CI, 1.07-7.01 and 1.96, 95% CI, 1.05-3.67, respectively). CONCLUSIONS: In a retrospective cohort study, we show that appendectomy, body mass index, and endoscopic activity at the time of diagnosis of proctitis are associated with an increased risk of extension. In addition, our data suggest that extenders are more likely to require immunosuppressive or biologic therapy.

Comparison of Stromal Vascular Fraction with or Without a Novel Bioscaffold to Fibrin Glue in a Porcine Model of Mechanically Induced Anorectal Fistula.

BACKGROUND: Anorectal fistulas (ARFs) are a common, devastating, event in the life of a patient with Crohn's disease. ARFs occur in up to 50% of patients with Crohn's disease. Treatment begins with surgical drainage of the initial abscess, followed by antibiotic therapy, then anti-inflammatory medications. If medical therapy fails to close the fistula tract, surgical intervention is often pursued. Surgery incurs risk of incontinence because of sphincter injury. Increasingly, the role of cell-based therapy is being investigated in ARFs. We evaluated the role a bioabsorbable scaffold plays in delivering cell-based therapy using a porcine model of AFR. METHODS: ARFs were mechanically created and matured by setons. After 28 days, setons were removed; periaortic fat was harvested and processed for stromal vascular fraction (SVF). The cells were labeled with a membrane stain for later identification, then injected into the fistula or implanted through scaffold. Fistulas not treated with cells were injected with fibrin glue. Animals were monitored visually for healing at weeks 2 and 4, then euthanized to evaluate fistulas for histologic healing. RESULTS: All fistulas (6/6) treated with SVF + scaffolds healed by week 2, compared with only 4/6 with just SVF and 0/5 treated with fibrin glue. Scaffolds retained SVF within the fistula tract more readily than injection method and SVF+scaffold treatment accelerated the healing process. Robust neovascularization was also seen in fistulas treated with SVF+scaffold. No adverse events occurred. CONCLUSIONS: Scaffold technology may improve cell-based therapy healing rates for Crohn's ARFs. This advance should be investigated by human trials.

Gut Microbiome Function Predicts Response to Anti-integrin Biologic Therapy in Inflammatory Bowel Diseases.

The gut microbiome plays a central role in inflammatory bowel diseases (IBDs) pathogenesis and propagation. To determine whether the gut microbiome may predict responses to IBD therapy, we conducted a prospective study with Crohn's disease (CD) or ulcerative colitis (UC) patients initiating anti-integrin therapy (vedolizumab). Disease activity and stool metagenomes at baseline, and weeks 14, 30, and 54 after therapy initiation were assessed. Community α-diversity was significantly higher, and Roseburia inulinivorans and a Burkholderiales species were more abundant at baseline among CD patients achieving week 14 remission. Several significant associations were identified with microbial function; 13 pathways including branched chain amino acid synthesis were significantly enriched in baseline samples from CD patients achieving remission. A neural network algorithm, vedoNet, incorporating microbiome and clinical data, provided highest classifying power for clinical remission. We hypothesize that the trajectory of early microbiome changes may be a marker of response to IBD treatment.

Distance to Specialist Care and Disease Outcomes in Inflammatory Bowel Disease.

BACKGROUND: Optimal treatment of inflammatory bowel disease (IBD) requires specialized health care. Patients frequently travel long distances to obtain care for IBD, which may hinder regular care and affect outcomes adversely. METHODS: This study included patients with established Crohn's disease or ulcerative colitis receiving care at a single referral center between January 2005 and August 2016. Distance to our health care center from the zip code of residence was determined for each patient and classified into quartiles. Our primary outcome was need for IBD-related surgery with secondary outcomes being need for biological and immunomodulator therapy. Logistic regression models adjusting for relevant covariates examined the independent association between travel distance and patient outcomes. RESULTS: Our study included 2136 patients with IBD (1197 Crohn's disease, 939 ulcerative colitis), among which just over half were women (52%), and the mean age was 41 years. The mean distance from our hospital was 2.5, 8.8, 22.0, and 50.8 miles for the first (most proximal) through fourth (most distant), respectively. We observed a statistically significant and meaningful higher risk among patients in the most distant quartile in the need for immunomodulator use (OR, 1.69; 95% CI, 1.29-2.22), biological therapy (OR, 2.19; 95% CI, 1.69-2.85), and surgery (OR, 2.44; 95% CI, 1.80-3.32). Differences remained significant on multivariable analysis and by type of IBD. CONCLUSIONS: Greater distance to referral health care center was associated with increased risk for needing IBD-related surgery in patients with Crohn's disease or ulcerative colitis.

Management of Inflammatory Bowel Disease in the Elderly Patient: Challenges and Opportunities.

The population of older patients with inflammatory bowel disease (IBD) continues to grow, partly reflecting the aging global population in general. The debilitating effects of IBD compound age-related decrements in health and functional capacity, and make the medical management of older patients with Crohn's disease and ulcerative colitis distinctly challenging to clinicians. Here, we review the recent literature describing the pharmacologic management of IBD in this population, with focus on the safety, tolerability, and efficacy of common treatment options, such as steroids, immunomodulators, tumor necrosis factor-α antagonists, and integrin antagonists; surgical interventions in older patients are also discussed. Few studies have systematically and prospectively evaluated the clinical challenges in the medical management of IBD in this patient population, leaving a limited evidence base to which clinicians can turn to for guidance. Treatment patterns may thus be suboptimal. For example, prolonged steroid use in the elderly was found to be common, causing significant morbidity from side effects in a particularly vulnerable population. Finally, within the context of a limited evidence base, we discuss common treatment scenarios to define the parameters within which physicians can individualize care for older patients with IBD. Overall, older patients with IBD are at higher risk of adverse events and less treatment responsiveness compared with younger patients, underscoring the need for future studies to fully characterize appropriate treatment courses for this population.

Imaging in Patients with Crohn's Disease: Trends in Abdominal CT/MRI Utilization and Radiation Exposure Considerations over a 10-Year Period.

PURPOSE: To study the trends in utilization of computed tomography (CT) and magnetic resonance imaging (MRI) in patients with Crohn's disease and to evaluate changes in CT radiation exposure over a 10-year period. METHODS: In this institutional review board-approved single-institution retrospective study, we included patients who underwent CT and MRIs for evaluation of Crohn's disease between 2006 and 2015. A total of 3196 CTs and 1924 MR scans were performed in 2156 patients (mean age: 34.8 ± 17.71 yr; range: 3-91 yr) for initial diagnosis or follow-up of Crohn's disease between 2006 and 2015. Trends in CT/MR utilization was assessed by comparing the volume of CT/MRI studies performed each year. The changes in CT radiation exposure over the study period were estimated and compared. RESULTS: The annual combined CT/MR utilization demonstrated a 1.9-fold rise over the last decade (2006: n = 358, 2015: n = 681, P < 0.001, r = 0.96). It was predominantly because of a substantial growth (9.2-fold increase) in the MR scan volume (2006: n = 37, 2015: n = 341, P < 0.001, r = 0.93), whereas CT volume did not show significant change (2006: n = 321, 2015: n = 340, P = 0.6). Over this same period, there was a 59.4% reduction in mean radiation exposure (2006: CT dose indexvol 16.9 ± 7.1 mGy, 2015: CT dose indexvol 6.87 ± 4.62 mGy, P < 0.001). CONCLUSIONS: A 9-fold growth in annual MR scan volume contributed to a nearly 2-fold rise in yearly cross-sectional imaging utilization in Crohn's patients between 2006 and 2015. Rising trend in imaging utilization paralleled a 60% reduction of CT radiation exposure.

Risk of colorectal cancer in Asian patients with ulcerative colitis: a systematic review and meta-analysis.

BACKGROUND: The increased risk of colorectal cancer in ulcerative colitis is well known. The risk of sporadic colorectal cancer in Asian populations is considered low and risk estimates of colorectal cancer related to ulcerative colitis from Asia vary. This meta-analysis is an Asian perspective on the risk of colorectal cancer related to ulcerative colitis. METHODS: We searched PubMed and Embase for terms related to colorectal cancer in ulcerative colitis from inception to July 1, 2016. The search for published articles was done by country for all countries in Asia. We included studies with information on the prevalence and cumulative risk of colorectal cancer at various timepoints. A random-effects meta-analysis was done to calculate the pooled prevalence as well as a cumulative risk at 10 years, 20 years, and 30 years of disease. FINDINGS: Our search identified 2575 articles; of which 44 were eligible for inclusion. Our analysis included a total of 31 287 patients with ulcerative colitis with a total of 293 reported colorectal cancers. Using pooled prevalence estimates from various studies, the overall prevalence was 0·85% (95% CI 0·65-1·04). The risks for colorectal cancer were 0·02% (95% CI 0·00-0·04) at 10 years, 4·81% (3·26-6·36) at 20 years, and 13·91% (7·09-20·72) at 30 years. Subgroup analysis by stratifying the studies according to region or period of the study did not reveal any significant differences. INTERPRETATION: We found the risk of colorectal cancer in Asian patients with ulcerative colitis was similar to recent estimates in Europe and North America. Adherence to screening is therefore necessary. Larger population-based, prospective studies are required for better estimates of the risk. FUNDING: Indo-US Science and Technology Forum.

Predictors of Clinical Response and Remission at 1 Year Among a Multicenter Cohort of Patients with Inflammatory Bowel Disease Treated with Vedolizumab.

BACKGROUND: Vedolizumab (VDZ) has demonstrated long-term efficacy in Crohn's disease (CD) and ulcerative colitis (UC) in phase III trials. AIMS: Our aim was to evaluate the efficacy of VDZ at week 54 in inflammatory bowel disease (IBD) in a multicenter cohort of patients. METHODS: Adult patients completing induction therapy with VDZ were eligible for this study. Clinical response and remission was assessed using the Harvey-Bradshaw Index (HBI) for CD, the Simple Clinical Colitis Activity Index for UC and physician assessment. RESULTS: Among 136 total patients (96 CD and 40 UC), 76 (56%) demonstrated clinical response or remission at week 54. In univariate analysis, for patients with CD concomitant initiation of immunomodulator therapy (2.71, 95% CI 1.11-6.57), the addition of an immunomodulator (OR 11.49, 3.16-41.75) and CRP < 3 (4.92, 95% CI 1.99-12.15) was associated with increased odds of clinical response or remission at week 54. For UC patients, hospitalization after VDZ induction was associated with decreased odds of response or remission at week 54 (OR 0.22, 95% CI 0.05-0.88). On multivariate analysis in CD, addition of an immunomodulator (OR 8.33, 95% CI 2.15-32.26) remained significant predictors of clinical response or remission at week 54. CONCLUSIONS: Among a multicenter cohort of patients with IBD demonstrating primary response to VDZ, the addition of combination therapy with an immunomodulator is a significant predictor of clinical response or remission at week 54 in patients with CD.

Efficacy and Safety of Vedolizumab in Ulcerative Colitis and Crohn's Disease Patients Stratified by Age.

INTRODUCTION: The efficacy and safety of vedolizumab, a gut-selective α4ß7 integrin antibody, were demonstrated in the GEMINI 1 and GEMINI 2 clinical trials of adults aged 18-80 years. We investigated the efficacy and safety of vedolizumab in patients stratified by age from the GEMINI trials. METHODS: Safety and efficacy, including clinical response, clinical remission, and corticosteroid-free remission, at week 6 and/or 52 were determined post hoc in patients aged <35, 35 to <55, and ≥55 years. RESULTS: At baseline, 353, 412, and 130 ulcerative colitis (UC) and 582, 443, and 90 Crohn's disease (CD) patients were aged <35, 35 to <55, and ≥55. Of these patients, 56 were aged ≥65 years (UC: 33, CD: 23). Trends favoring vedolizumab over placebo were observed for most efficacy endpoints irrespective of patient age; some variability between subgroups was observed. Safety profiles of vedolizumab and placebo were similar in all age groups. Vedolizumab-treated patients aged ≥55 had the lowest incidence of serious infections (0.9 per 100 person-years) and adverse events leading to hospitalization (14.8 per 100 person-years). There were no age-related differences in the incidence of adverse hematological events, malignancy, or death. CONCLUSIONS: The safety and efficacy of vedolizumab in patients with UC or CD were similar for all age groups. The number of patients in the oldest age group in these analyses was small; thus further studies of vedolizumab in larger cohorts of elderly patients are warranted. FUNDING: Millennium Pharmaceuticals, Inc. (d/b/a Takeda Pharmaceuticals International Co.).

Older Age- and Health-related Quality of Life in Inflammatory Bowel Diseases.

BACKGROUND: The burden of inflammatory bowel disease (IBD) in the older population is increasing. Older-onset disease is associated with reduced use of immunosuppressive medications. In addition, older patients may be more vulnerable to the effect of disease-related symptoms and consequently may experience worse health-related quality of life (HRQoL) compared with younger patients. METHODS: This prospective study included a cohort of patients with Crohn's disease and ulcerative colitis recruited from a single center. All patients completed the Short Inflammatory Bowel Disease Questionnaire (SIBDQ) and the short form-12 (SF-12) questionnaire yielding general physical health (PCS) and mental health component scale subscores (MCS). Patients older than 60 years were compared with those younger than 60 years using multivariable regression analysis. RESULTS: Our study included 1607 patients, among whom 186 were older than 60 at the time of assessment. Older patients were more likely to have isolated colonic disease and less likely to use immunosuppressive therapy. On multivariable analysis, older patients with IBD had higher SIBDQ (2.34, 95% confidence interval, 0.82-3.87) and SF-12 mental subscores (3.78, 95% confidence interval, 2.26-5.30), but lower physical HRQoL (-1.80, 95% confidence interval, -3.21 to -0.38). There was no difference in the SIBDQ and PCS scores between older patients and newly diagnosed IBD or with established disease. CONCLUSIONS: Older age was associated with modestly higher SIBDQ and mental HRQoL scores, but lower physical HRQoL. Comprehensive care of the older patient with IBD should include assessment of factors impairing physical quality of life to ensure appropriate interventions.