Long-term outcome of enterocutaneous fistula in patients with Crohn's disease treated with anti-TNF therapy: a cohort study from the GETAID.

Objectives: Although anti-tumor necrosis factor (TNF) therapy is the treatment of choice for perianal fistulizing Crohn's disease (CD), the efficacy and safety of anti-TNF therapy in enterocutaneous fistula (ECF) remains unclear.

Methods: Between January 2008 and December 2009, we retrospectively reviewed the outcomes of all CD patients with ECF (excluding perianal fistula) treated with anti-TNF therapy followed up in Groupe d'Etude Thérapeutique des Affections Inflammatoires du tube Digestif (GETAID) centers. ECF closure and tolerance of anti-TNF therapy were studied using univariate and multivariate analyses.

Analysis of single nucleotide polymorphisms in the region of CLDN2-MORC4 in relation to inflammatory bowel disease.

Aim: To investigate a possible genetic influence of claudin (CLDN)1, CLDN2 and CLDN4 in the etiology of inflammatory bowel disease.

Methods: Allelic association between genetic regions of CLDN1, CLDN2 or CLDN4 and patients with inflammatory bowel disease, Crohn's disease (CD) or ulcerative colitis were investigated using both a case-control study approach (one case randomly selected from each of 191 Swedish inflammatory bowel disease families and 333 controls) and a family-based study (463 non-Swedish European inflammatory bowel disease -families). A nonsynonymous coding single nucleotide polymorphism in MORC4, located on the same linkage block as CLDN2, was investigated for association, as were two novel CLDN2 single nucleotide polymorphism markers, identified by resequencing.

Genotype/phenotype analyses for 53 Crohn's disease associated genetic polymorphisms.

Background & Aims: Recent studies reported a role for more than 70 genes or loci in the susceptibility to Crohn's disease (CD). However, the impact of these associations in clinical practice remains to be defined. The aim of the study was to analyse the relationship between genotypes and phenotypes for the main 53 CD-associated polymorphisms.

Ciclosporin versus infliximab in patients with severe ulcerative colitis refractory to intravenous steroids: a parallel, open-label randomised controlled trial.

Background: Ciclosporin and infliximab are potential rescue treatments to avoid colectomy in patients with acute severe ulcerative colitis refractory to intravenous corticosteroids. We compared the efficacy and safety of these drugs for this indication.

Methods: In this parallel, open-label, randomised controlled trial, patients were aged at least 18 years, had an acute severe flare of ulcerative colitis defined by a Lichtiger score greater than 10 points, and had been given an unsuccessful course of high-dose intravenous steroids.

Challenges to the design, execution, and analysis of randomized controlled trials for inflammatory bowel disease.

Treatment of inflammatory bowel disease has greatly improved with the development of targeted, monoclonal antibody-based therapies. Tumor necrosis factor antagonists are frequently used to treat patients with Crohn's disease or ulcerative colitis, but they have side effects and their efficacy often decreases with use. New, more effective drugs are therefore needed and in development.

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.

Clinical predictors at diagnosis of disabling pediatric Crohn's disease.

Background: Identification of children with Crohn's disease (CD) at high risk of disabling disease would be invaluable in guiding initial therapy. Our study aimed to identify predictors at diagnosis of a subsequent disabling course in a population-based cohort of patients with pediatric-onset CD.

Methods: Among 537 patients with pediatric CD diagnosed at <17 years of age, 309 (57%) with 5-year follow-up were included.

High frequency of fatal haemophagocytic lymphohistiocytosis syndrome in enteropathy-associated T cell lymphoma.

Introduction: Enteropathy-associated T-cell lymphoma is a rare form of T-cell lymphoma associated with a poor prognosis and the relative ineffectiveness of standard chemotherapy. The occurrence of haemophagocytic lymphohistiocytosis has been reported only once with this entity.

Patients And Methods: A retrospective study of 15 patients with enteropathy-associated T-cell lymphoma (type 1 in 12), followed-up in our units, since 1985.

Recommendations for the treatment of Crohn's disease with tumor necrosis factor antagonists: an expert consensus report.

Background: Symptom relief is the traditional treatment goal in Crohn's disease (CD). New goals including mucosal healing and bowel preservation are now achievable with tumor necrosis factor (TNF) antagonists. Infliximab and adalimumab are approved as second-line treatments for severe, active CD.

Developing an instrument to assess the endoscopic severity of ulcerative colitis: the Ulcerative Colitis Endoscopic Index of Severity (UCEIS).

Background: Variability in endoscopic assessment necessitates rigorous investigation of descriptors for scoring severity of ulcerative colitis (UC).

Objective: To evaluate variation in the overall endoscopic assessment of severity, the intra- and interindividual variation of descriptive terms and to create an Ulcerative Colitis Endoscopic Index of Severity which could be validated.

Design: A two-phase study used a library of 670 video sigmoidoscopies from patients with Mayo Clinic scores 0-11, supplemented by 10 videos from five people without UC and five hospitalised patients with acute severe UC.

Maintenance of remission among patients with Crohn's disease on antimetabolite therapy after infliximab therapy is stopped.

Background & Aims: It is important to determine whether infliximab therapy can be safely interrupted in patients with Crohn's disease who have undergone a period of prolonged remission. We assessed the risk of relapse after infliximab therapy was discontinued in patients on combined maintenance therapy with antimetabolites and identified factors associated with relapse.

Methods: We performed a prospective study of 115 patients with Crohn's disease who were treated for at least 1 year with scheduled infliximab and an antimetabolite and had been in corticosteroid-free remission for at least 6 months.

Assessing patients' satisfaction with anti-TNFα treatment in Crohn's disease: qualitative steps of the development of a new questionnaire.

Purpose: To develop a self-administered questionnaire assessing patients' satisfaction with treatments in Crohn's disease for use in clinical research and epidemiological studies.

Patients And Methods: Semi-directive interviews (16) were conducted with patients with severe Crohn's disease treated with anti-tumor necrosis factor alpha (anti-TNFα). Transcripts were analyzed and concepts related to satisfaction with treatment were extracted and organized into a model.

Increased risk for nonmelanoma skin cancers in patients who receive thiopurines for inflammatory bowel disease.

Background & Aims: Patients with inflammatory bowel disease (IBD) who have been exposed to thiopurines might have an increased risk of skin cancer. We assessed this risk among patients in France.

Methods: We performed a prospective observational cohort study of 19,486 patients with IBD, enrolled from May 2004 to June 2005, who were followed up until December 31, 2007.

TNF alpha antagonist therapy and safety monitoring.

Objectives: To develop and/or update fact sheets about TNFα antagonists treatments, in order to assist physicians in the management of patients with inflammatory joint disease.

Methods: 1. selection by a committee of rheumatology experts of the main topics of interest for which fact sheets were desirable; 2.

Activation of the receptor NKG2D leads to production of Th17 cytokines in CD4+ T cells of patients with Crohn's disease.

Background & Aims: The natural killer group 2 member D (NKG2D) is a stimulatory receptor expressed on a subset of mucosal and peripheral CD4+ T cells in patients with Crohn's disease (CD) and other inflammatory diseases. Ligand activation of NKG2D in patients induces CD4+ T cells to release T-helper (Th) 1 cytokines and become cytotoxic. We investigated the Th17 cytokines produced by T cells that express NKG2D in blood and intestinal mucosa samples from patients with CD.

Development of the Crohn's disease digestive damage score, the Lémann score.

Crohn's disease (CD) is a chronic progressive destructive disease. Currently available instruments measure disease activity at a specific point in time. An instrument to measure cumulative structural damage to the bowel, which may predict long-term disability, is needed.

Crohn's disease recurrence after total proctocolectomy with definitive ileostomy.

Background: Total proctocolectomy with definitive ileostomy is the ultimate treatment for refractory colonic Crohn's disease (CD). Aim of the study was to report the outcome of Crohn's disease patients after total proctocolectomy with definitive ileostomy.

Patients And Methods: Between 1990 and 2005, 55 patients underwent total proctocolectomy with definitive ileostomy for Crohn's disease in our institution.

Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47.

Genome-wide association studies and candidate gene studies in ulcerative colitis have identified 18 susceptibility loci. We conducted a meta-analysis of six ulcerative colitis genome-wide association study datasets, comprising 6,687 cases and 19,718 controls, and followed up the top association signals in 9,628 cases and 12,917 controls. We identified 29 additional risk loci (P < 5 × 10(-8)), increasing the number of ulcerative colitis-associated loci to 47.

Long-term outcome of treatment with infliximab in pediatric-onset Crohn's disease: a population-based study.

Background: We examined short- and long-term benefits and safety of infliximab (IFX) in a population-based cohort of Crohn's disease (CD) patients <17 years old at diagnosis.

Methods: The following parameters were assessed: short- and long-term efficacy of IFX, impact of drug efficacy, and mode of administration on rate of resection surgery, growth and nutritional catch-up, and adverse events (AEs).

Results: In all, 120 patients (69 female) required IFX with a median duration of 32 months (Q1 = 8-Q3 = 60).

Appropriate maintenance treatment for Crohn's disease: Results of a multidisciplinary international expert panel - EPACT II.

Introduction: Biological therapy has dramatically changed management of Crohn's disease (CD). New data have confirmed the benefit and relative long-term safety of anti-TNFα inhibition as part of a regular scheduled administration programme. The EPACT appropriateness criteria for maintenance treatment after medically-induced remission (MIR) or surgically-induced remission (SIR) of CD thus required updating.

Resequencing of positional candidates identifies low frequency IL23R coding variants protecting against inflammatory bowel disease.

Genome-wide association studies (GWAS) have identified dozens of risk loci for many complex disorders, including Crohn's disease. However, common disease-associated SNPs explain at most ∼20% of the genetic variance for Crohn's disease. Several factors may account for this unexplained heritability, including rare risk variants not adequately tagged thus far in GWAS.

Report of the ECCO pathogenesis workshop on anti-TNF therapy failures in inflammatory bowel diseases: definitions, frequency and pharmacological aspects.

The first ECCO pathogenesis workshop focused on anti-TNF therapy failures in inflammatory bowel diseases (IBDs). The overall objective was to better understand and explore primary non response and loss of response to anti-TNF agents in IBD. The outcome of this workshop is presented into two parts.

Pregnancy outcome in patients with inflammatory bowel disease treated with thiopurines: cohort from the CESAME Study.

Background And Aims: Few studies have been conducted addressing the safety of thiopurine treatment in pregnant women with inflammatory bowel disease (IBD). The aim of this study was to evaluate the pregnancy outcome of women with IBD who have been exposed to thiopurines.

Methods: 215 pregnancies in 204 women were registered and documented in the CESAME cohort between May 2004 and October 2007.

Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci.

We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 × 10⁻⁸). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP.