The role of centralized reading of endoscopy in a randomized controlled trial of mesalamine for ulcerative colitis.

Background & Aims: Interobserver differences in endoscopic assessments contribute to variations in rates of response to placebo in ulcerative colitis (UC) trials. We investigated whether centralized review of images could reduce these variations.

Methods: We performed a 10-week, randomized, double-blind, placebo-controlled study of 281 patients with mildly to moderately active UC, defined by an Ulcerative Colitis Disease Activity Index (UCDAI) sigmoidoscopy score ≥2, that evaluated the efficacy of delayed-release mesalamine (Asacol 800-mg tablet) 4.

A randomized controlled trial of the efficacy and safety of CCX282-B, an orally-administered blocker of chemokine receptor CCR9, for patients with Crohn's disease.

Unlabelled: CCX282-B, also called vercirnon, is a specific, orally-administered chemokine receptor CCR9 antagonist that regulates migration and activation of inflammatory cells in the intestine. This randomized, placebo-controlled trial was conducted to evaluate the safety and efficacy of CCX282-B in 436 patients with Crohn's disease. Crohn's Disease Activity Index (CDAI) scores were 250-450 and C-reactive protein >7.

Correlation between the endoscopic and histologic score in assessing the activity of ulcerative colitis.

Background: In routine practice, scoring of activity and severity of ulcerative colitis is based on combined clinical and endoscopic assessment. Histology also allows sensitive scoring of ulcerative colitis activity. The correlation between endoscopy and histology has not been investigated thoroughly.

Certolizumab pegol in the treatment of Crohn's disease.

Introduction: The introduction of antibodies directed against tumour necrosis factor (anti-TNF) has dramatically changed the concept of treating patients with Crohn's disease (CD). Unfortunately, the long-term efficacy of anti-TNF agents may be hampered by immunogenicity. The availability of more anti-TNF agents in the therapeutic armamentarium would therefore be of great benefit in patients loosing response to another anti-TNF.

Antibody response to infliximab and its impact on pharmacokinetics can be transient.

Objectives: Infliximab (IFX) is successfully used in the treatment of inflammatory bowel diseases but some patients generate antibodies to IFX (ATI) jeopardizing the pharmacokinetics of the drug. Little is known about the factors influencing ATI formation and whether or not this immune reaction is permanent. Our aim was to investigate the kinetics of ATI formation and drug levels in relation to inflammatory markers and the clinical evolution of the patients.

Effects of infliximab therapy on transmural lesions as assessed by magnetic resonance enteroclysis in patients with ileal Crohn's disease.

Background And Aims: Anti TNF therapy induces mucosal healing in patients with Crohn's disease, but the effects on transmural inflammation in the ileum are not well understood. Magnetic resonance-enteroclysis (MRE) offers excellent imaging of transmural and peri-enteric lesions in Crohn's ileitis and we aimed to study its responsiveness to anti TNF therapy.

Methods: In this multi-center prospective trial, anti TNF naïve patients with ileal Crohn's disease and with increased CRP and contrast enhanced wall thickening received infliximab 5 mg/kg at weeks 0, 2 and 6, and q8 weeks maintenance MRE was performed at baseline, 2 weeks and 6 months and assessed based on a predefined MRE score of severity in ileal Crohn's Disease.

Metabolic profiling of the impact of oligofructose-enriched inulin in Crohn's disease patients: a double-blinded randomized controlled trial.

Objectives: Although intestinal dysbiosis is well established in Crohn's disease (CD), little is known about the microbial metabolic activity of CD patients. In this study, we compared the metabolite patterns of the CD patients with profiles from healthy controls (HCs) and correlated them to disease activity and bacterial composition. In addition, the influence of the prebiotic oligofructose-enriched inulin (OF-IN) on the CD metabolites profile was evaluated.

Butyricicoccus pullicaecorum in inflammatory bowel disease.

Objective: Many species within the phylum Firmicutes are thought to exert anti-inflammatory effects. We quantified bacteria belonging to the genus Butyricicoccus in stools of patients with ulcerative colitis (UC) and Crohn's disease (CD). We evaluated the effect of Butyricicoccus pullicaecorum in a rat colitis model and analysed the ability to prevent cytokine-induced increases in epithelial permeability.

Genetic factors conferring an increased susceptibility to develop Crohn's disease also influence disease phenotype: results from the IBDchip European Project.

Objective: Through genome-wide association scans and meta-analyses thereof, over 70 genetic loci (Crohn's disease (CD) single nucleotide polymorphisms (SNPs)) are significantly associated with CD. We aimed to investigate the influence of CD-SNPs and basic patient characteristics on CD clinical course, and develop statistical models to predict CD clinical course.

Design: This retrospective study included 1528 patients with CD with more than 10 years of follow-up from eight European referral hospitals.

Prognostic value of serologic and histologic markers on clinical relapse in ulcerative colitis patients with mucosal healing.

Objectives: Endoscopic mucosal healing is a key endpoint for the treatment of ulcerative colitis (UC). The role of microscopic activity in predicting disease relapse has not been fully assessed. We aimed to investigate the predictive role of serologic and histologic markers on disease relapse in UC patients with endoscopically inactive disease.

Interleukin-15 receptor α expression in inflammatory bowel disease patients before and after normalization of inflammation with infliximab.

Interleukin-15 (IL-15) is a pro-inflammatory cytokine thought to contribute to the inflammation in inflammatory bowel diseases (IBD). The specific receptor chain IL-15Rα can be expressed as a transmembranous signalling receptor, or can be cleaved by a disintegrin and metalloprotease domain 17 (ADAM17) into a neutralizing, soluble receptor (sIL-15Rα). The aim of this study is to evaluate the expression of IL-15Rα in ulcerative colitis (UC) and Crohn's disease (CD) patients before and after infliximab (IFX) therapy.

Intersphincteric proctectomy with end-colostomy for anorectal Crohn's disease results in early and severe proximal colonic recurrence.

Background: Perianal Crohn's disease (CD) represents a more aggressive phenotype of inflammatory bowel disease and often coincides with proctocolitis. This study aims to assess the outcome of patients undergoing proctectomy with end-colostomy.

Methods: A retrospective outcome analysis of 10 consecutive patients who underwent intersphincteric proctectomy with end-colostomy between February 2007 and May 2011 was performed.

Genome-wide association analysis in primary sclerosing cholangitis and ulcerative colitis identifies risk loci at GPR35 and TCF4.

Unlabelled: Approximately 60%-80% of patients with primary sclerosing cholangitis (PSC) have concurrent ulcerative colitis (UC). Previous genome-wide association studies (GWAS) in PSC have detected a number of susceptibility loci that also show associations in UC and other immune-mediated diseases. We aimed to systematically compare genetic associations in PSC with genotype data in UC patients with the aim of detecting new susceptibility loci for PSC.

Towards a novel molecular classification of IBD.

Classifying IBD patients is important for decisions on the intensity of follow-up, therapy and mode of delivery. The most recent classification of Crohn's disease (CD) and ulcerative colitis (UC), the Montreal classification, is based on clinical grounds: for CD, the age at diagnosis and disease location and behavior and for UC, the age at diagnosis and the extent of disease. During the Working Party in 2005 in Montreal, it was judged by the panel of experts that a molecular reclassification using serology and/or genetic markers was too premature and not yet justified.

Paradoxical inflammation induced by anti-TNF agents in patients with IBD.

Anti-TNF antibodies have acquired a prominent place in the management of IBD (including Crohn's disease and ulcerative colitis), rheumatologic conditions (such as rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis) and psoriasis. They have a good safety profile, especially when contraindications such as demyelinating disease, active infections and/or abscesses are ruled out, and when necessary precautions to prevent reactivation of tuberculosis are taken. However, with increasing use of these agents, paradoxical adverse events have been reported.

Neutralization of membrane TNF, but not soluble TNF, is crucial for the treatment of experimental colitis.

Background: Agents neutralizing membrane tumor necrosis factor (mTNF) and soluble TNF (sTNF) are widely used for the treatment of inflammatory bowel disease (IBD). Neutralization of mTNF, however, is associated with increased susceptibility to infectious diseases. The aim of this study was to determine whether neutralization of sTNF exclusively, by the use of a dominant negative mutant of TNF (XENP1595), could reduce the severity of colitis in mice.

Classification of inflammatory bowel disease: the old and the new.

Purpose Of Review: Inflammatory bowel diseases (IBDs) are disorders of multifactorial cause that present as a multitude of phenotypes, clinical behaviours and severity. Crohn's disease and ulcerative colitis are considered as the two extremes of what is believed to be a spectrum of chronic gut inflammation and this separation is still the first classification used when confronted with an IBD patient. An accurate classification within IBD has several benefits, with respect to patient counselling, assessing risk for disease progression, and particularly with respect to choosing the most appropriate therapy for an individual patient.

Management of inflammatory bowel disease in pregnancy.

Background And Aims: Inflammatory bowel disease (IBD) is a chronic disease affecting mainly young people in their reproductive years. IBD therefore has a major impact on patients' family planning decisions. Management of IBD in pregnancy requires a challenging balance between optimal disease control and drug safety considerations.

Endoscopic improvement of mucosal lesions in patients with moderate to severe ileocolonic Crohn's disease following treatment with certolizumab pegol.

Objective: To evaluate the efficacy of certolizumab pegol (CZP) in improving endoscopic lesions in patients with active ileocolonic Crohn's disease (CD).

Methods: This phase IIIB multicentre open-label clinical trial enrolled 89 adult patients with active endoscopic disease (ulceration in ≥2 intestinal segments with a Crohn's Disease Endoscopic Index of Severity (CDEIS) score ≥8 points). Patients received subcutaneous CZP 400 mg at weeks 0, 2 and 4 and every 4 weeks up to week 52.

Extended analysis of a genome-wide association study in primary sclerosing cholangitis detects multiple novel risk loci.

Background & Aims: A limited number of genetic risk factors have been reported in primary sclerosing cholangitis (PSC). To discover further genetic susceptibility factors for PSC, we followed up on a second tier of single nucleotide polymorphisms (SNPs) from a genome-wide association study (GWAS).

Methods: We analyzed 45 SNPs in 1221 PSC cases and 3508 controls.