Shorter Disease Duration Is Associated With Higher Rates of Response to Vedolizumab in Patients With Crohn's Disease But Not Ulcerative Colitis.

Background & aimsPatients with Crohn's disease (CD), but not ulcerative colitis (UC), of shorter duration have higher rates of response to tumor necrosis factor (TNF) antagonists than patients with longer disease duration. Little is known about the association between disease duration and response to other biologic agents. We aimed to evaluate response of patients with CD or UC to vedolizumab, stratified by disease duration.MethodsWe analyzed data from a retrospective, multicenter, consortium of patients with CD (n = 650) or UC (n = 437) treated with vedolizumab from May 2014 through December 2016. Using time to event analyses, we compared rates of clinical remission, corticosteroid-free remission (CSFR), and endoscopic remission between patients with early-stage (≤2 years duration) and later-stage (>2 years) CD or UC. We used Cox proportional hazards models to identify factors associated with outcomes.ResultsWithin 6 months initiation of treatment with vedolizumab, significantly higher proportions of patients with early-stage CD, vs later-stage CD, achieved clinical remission (38% vs 23%), CSFR (43% vs 14%), and endoscopic remission (29% vs 13%) (P < .05 for all comparisons). After adjusting for disease-related factors including previous exposure to TNF antagonists, patients with early-stage CD were significantly more likely than patients with later-stage CD to achieve clinical remission (adjusted hazard ratio [aHR], 1.59; 95% CI, 1.02-2.49), CSFR (aHR, 3.39; 95% CI, 1.66-6.92), and endoscopic remission (aHR, 1.90; 95% CI, 1.06-3.39). In contrast, disease duration was not a significant predictor of response among patients with UC.ConclusionsPatients with CD for 2 years or less are significantly more likely to achieve a complete response, CSFR, or endoscopic response to vedolizumab than patients with longer disease duration. Disease duration does not associate with response vedolizumab in patients with UC

Review article: bacteriophages in gastroenterology-from biology to clinical applications

BACKGROUND: The gut microbiota plays an important role in the pathogenesis of several gastrointestinal diseases. Its composition and function are shaped by host-microbiota and intra-microbiota interactions. Bacteriophages (phages) are viruses that target bacteria and have the potential to modulate bacterial communities. AIMS: To summarise phage biology and the clinical applications of phages in gastroenterology METHODS: PubMed was searched to identify relevant studies. RESULTS: Phages induce bacterial cell lysis, integration of viral DNA into the bacteria and/or coexistence in a stable equilibrium. Bacteria and phages have co-evolved and their dynamic interactions are yet to be fully understood. The increasing need to modulate microbial communities (e.g., gut microbiota, multidrug-resistant bacteria) has been a strong stimulus for research in phages as an antibacterial therapy. In gastroenterology, phage therapy has been mainly studied in infectious diseases such as cholera. However, it is currently being explored in several other circumstances such as treating Clostridioides difficile colitis, targeting adherent-invasive Escherichia coli in Crohn's disease or eradicating Fusobacterium nucleatum in colorectal cancer. Overall, phage therapy has a favourable and acceptable safety profile. Presently, trials with phage therapy are ongoing in Crohn's disease. CONCLUSIONS: Phage therapy is a promising therapeutic tool against pathogenic bacteria in the fields of infectious diseases and gastroenterology. Randomised, placebo-controlled trials with phage therapy for gastroenterological diseases are ongoing.status: publishe

Diffusion and perfusion MRI quantification in ileal Crohn's disease

OBJECTIVES: To quantify intravoxel incoherent motion (IVIM)-DWI and dynamic contrast-enhanced (DCE)-MRI parameters in normal and abnormal ileal segments in Crohn's disease (CD) patients and to assess the association of these parameters with clinical and MRI-based measurements of CD activity. METHODS: In this prospective study, 27 CD patients (M/F 18/9, mean age 42 years) underwent MR enterography, including IVIM-DWI and DCE-MRI. IVIM-DWI and DCE-MRI parameters were quantified in normal and abnormal small bowel segments, the latter identified by the presence of inflammatory changes. MRI parameter differences between normal and abnormal bowel were tested using Wilcoxon signed-rank tests. IVIM-DWI and DCE-MRI parameters were correlated with clinical data (C-reactive protein, Harvey-Bradshaw Index), conventional MRI parameters (wall thickness, length of involvement) and MRI activity scores (MaRIA, Clermont). Diagnostic performance of (combined) parameters for differentiation between normal and abnormal bowel was determined using ROC analysis. RESULTS: The DCE-MRI parameters peak concentration C, upslope, area-under-the-curve at 60s (AUC60), K and v were significantly increased (p0.105). DCE-MRI parameters exhibited multiple significant correlations with wall thickness (C, upslope, AUC60, K; r range 0.431-0.664, p<0.025) and MaRIA/Clermont scores (C, AUC60, K; r range 0.441-0.617, p<0.021). Combined K+v+PF+ADC showed highest AUC (0.963) for differentiation between normal and abnormal bowel, while ADC performed best for individual parameters (AUC=0.800). CONCLUSIONS: DCE-MRI and IVIM-DWI, particularly when used in combination, are promising for non-invasive evaluation of small bowel CD. KEY POINTS: IVIM-DWI and DCE-MRI parameters were significantly different between normal and abnormal bowel segments in CD patients. • DCE-MRI parameters showed a significant association with wall thickness and MRI activity scores. • Combination of IVIM-DWI and DCE-MRI parameters led to the highest diagnostic performance for differentiation between normal and abnormal bowel segments, while ADC showed the highest diagnostic performance of individual parameters

Adherent-invasive Escherichia coli in inflammatory bowel disease

International audienceIntestinal microbiome dysbiosis has been consistently described in patients with IBD. In the last decades, Escherichia coli, and the adherent-invasive E coli (AIEC) pathotype in particular, has been implicated in the pathogenesis of IBD. Since the discovery of AIEC, two decades ago, progress has been made in unravelling these bacteria characteristics and its interaction with the gut immune system. The mechanisms of adhesion of AIEC to intestinal epithelial cells (via FimH and cell adhesion molecule 6) and its ability to escape autophagy when inside macrophages are reviewed here. We also explore the existing data on the prevalence of AIEC in patients with Crohn's disease and UC, and the association between the presence of AIEC and disease location, activity and postoperative recurrence. Finally, we highlight potential therapeutic strategies targeting AIEC colonisation of gut mucosa, including the use of phage therapy, bacteriocins and antiadhesive molecules. These strategies may open new avenues for the prevention and treatment of IBD in the future