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

Full list of Investigators is given at the end of the article.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. In phase 1, each of 10 investigators viewed 16/24 videos to assess agreement on the Baron score with a central reader and agreed definitions of 10 endoscopic descriptors. In phase 2, each of 30 different investigators rated 25/60 different videos for the descriptors and assessed overall severity on a 0-100 visual analogue scale. κ Statistics tested inter- and intraobserver variability for each descriptor. A general linear mixed regression model based on logit link and β distribution of variance was used to predict overall endoscopic severity from descriptors. Results: There was 76% agreement for 'severe', but 27% agreement for 'normal' appearances between phase I investigators and the central reader. In phase 2, weighted κ values ranged from 0.34 to 0.65 and 0.30 to 0.45 within and between observers for the 10 descriptors. The final model incorporated vascular pattern, (normal/patchy/ complete obliteration) bleeding (none/mucosal/luminal mild/luminal moderate or severe), erosions and ulcers (none/erosions/superficial/deep), each with precise definitions, which explained 90% of the variance (pR2, Akaike Information Criterion) in the overall assessment of endoscopic severity, predictions varying from 4 to 93 on a 100-point scale (from normal to worst endoscopic severity). Conclusion: The Ulcerative Colitis Endoscopic Index of Severity accurately predicts overall assessment of endoscopic severity of UC. Validity and responsiveness need further testing before it can be applied as an outcome measure in clinical trials or clinical practice.publishersversionPeer reviewe

Role of endoscopy in predicting the disease course in inflammatory bowel disease

Endoscopy provides a direct evaluation of mucosal lesions in inflammatory bowel disease (IBD), permitting the description of elementary lesions, their surface extent and severity. The severity of mucosal lesions directly reflects disease activity and may help to identify an aggressive behavior of the disease. Several studies have recently pointed out the potential role of endoscopy in the prediction of IBD outcome. Indeed, severe endoscopic lesions in Crohn’s disease (CD) patients, defined by deep and extensive ulcerations on at least one part of the colon, are associated with an increased risk of penetrating complication and surgery. Severe endoscopic lesions during severe attacks of ulcerative colitis (UC) are associated with an increased risk of colectomy in the short and long term. Severity of postoperative recurrence in CD may help to predict the risk of clinical relapse and need for further surgery. Achievement of mucosal healing, which can be obtained by administration of several types of drugs, is associated with a better outcome, less surgery and hospitalization. This review focuses on the assessment of endoscopic severity in CD and UC and on the impact of endoscopic severity on disease outcome. More specifically, we discuss how endoscopy can be used at different stages of IBD to predict the disease course and/or to adapt treatment strategies

Review article: remission rates achievable by current therapies for inflammatory bowel disease

International audienceBackground and Aim: To review remission rates with current medical treatments for inflammatory bowel disease (IBD). Methods We searched MEDLINE (source PUBMED, 1966 to January, 2011). Results Induction and maintenance of remission was observed in 20% (range, 9-29.5%) and 53% (range, 36.8-59.6%) of ulcerative colitis (UC) patients treated with oral 5-ASA derivatives. Induction of remission was noted in 52% (range, 48-58%) of Crohn's disease (CD) patients and 54% of UC patients treated with steroids in population-based cohorts. Maintenance of remission was reported in 71% (range, 56-95%) of CD patients on azathioprine over a 6 month to 2 year period and in 60% (range, 41.7-82.4%) in UC at one year or longer. Induction and maintenance of remission was noted in 39% (range, 19.3-66.7%) and 70% (range, 39-90%) of CD patients on methotrexate over a 40 week period. Induction of remission was reported in 32% (range, 25-48%), 26% (range, 18-36%) and 20% (range, 19-23%) of CD patients on infliximab, adalimumab and certolizumab pegol, respectively. The corresponding figures were 45% (range, 39-59%), 43% (range, 40-47%) and 47.9% at weeks 20-30 among initial responders. Induction of remission was observed in 33% (range, 27.5-38.8%) and 18.5% of UC patients on infliximab and adalimumab, respectively. Maintenance of remission was noted in 33% (range, 25.6-36.9%) of UC patients on infliximab at week 30. Approximately one-fifth of CD and UC patients treated with biologicals require intestinal resection after 2-5 years in referral-center studies. Conclusion In the era of biologics, the proportion of patients not entering remission remains high

Incidence of nodular regenerative hyperplasia in inflammatory bowel disease patients treated with azathioprine.

International audienceBACKGROUND: Nodular regenerative hyperplasia (NRH) is a rare hepatic disorder that may lead to severe portal hypertension. Cases of NRH have been reported in patients receiving thiopurines for inflammatory bowel disease (IBD). Since azathioprine (AZA) is used more and more frequently as a maintenance treatment in IBD, the risk of NRH must be known. The objective of this study was to evaluate the prevalence of NRH and its predictive factors in IBD patients treated with AZA. MATERIALS AND METHODS: From the same tertiary referral center, 1888 consecutive IBD patients treated with AZA were studied. Clinical diagnosis of NRH was proven by liver biopsy in all cases except one. The cumulative risk of NRH was estimated with the Kaplan-Meier method. Factors associated with NRH were tested independently with the log-rank method and multivariate proportional hazards model with time-dependent covariates. RESULTS: Fifteen patients developed NRH in a median treatment duration of 52.4 months (SE 1.6). The cumulative incidence of NRH was 1.28±0.45% at 10 years. Only two variables were independently associated with NRH occurrence: male gender (P=0.0001, hazard ratio [HR] 8.5, 95% confidence interval [CI] 1.9-37.9) and small bowel resection≥50 cm (P<0.0001, HR 6.6, 95% CI 2.2-20.0), either prior to or after AZA initiation. CONCLUSIONS: The risk of developing NRH during AZA treatment is low. This study suggests that male patients with small bowel resection≥50 cm constitute the group with the higher risk of developing NRH while treated with AZA

Severe skin lesions cause patients with inflammatory bowel disease to discontinue anti-tumor necrosis factor therapy.

BACKGROUND & AIMS: Psoriasiform and eczematiform lesions are associated with anti-tumor necrosis factor (TNF)-alpha therapies. We assessed clinical characteristics, risk factors, and outcomes of skin disease in patients with inflammatory bowel diseases that presented with psoriasiform and eczematiform lesions induced by anti-TNF-alpha agents. METHODS: We studied 85 patients (69 with Crohn's disease, 15 with ulcerative colitis, and 1 with indeterminate colitis; 62 women) with inflammatory skin lesions (62 psoriasiform and 23 eczematiform lesions). RESULTS: Twenty-four patients had a history of inflammatory skin lesions and 15 had a familial history of inflammatory skin disease. Locations of eczematiform lesions varied whereas scalp and flexural varieties were mostly psoriasiform. Skin lesions emerged but inflammatory bowel disease was quiescent in 69 patients following treatment with any type of anti-TNF-alpha agent (60 with infliximab, 20 with adalimumab, and 5 with certolizumab). Topical therapy resulted in partial or total remission in 41 patients. Patients with psoriasiform lesions that were resistant to topical therapy and that changed anti-TNF-alpha therapies once or twice developed recurring lesions. Overall, uncontrolled skin lesions caused 29 patients to stop taking TNF-alpha inhibitors. CONCLUSIONS: Inflammatory skin lesions following therapy with TNF-alpha inhibitors occurred most frequently among women and patients with a personal or familial history of inflammatory skin disease; lesions did not correlate with intestinal disease activity. Recurring and intense skin lesions caused 34% of patients in this study to discontinue use of anti-TNF-alpha agents

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. However, many agents that appeared to be promising in preclinical studies have failed to show efficacy in clinical trials. We discuss possible reasons for the failures of these reagents in trials, which include the high rate of response to placebo, an inadequate range of doses, inappropriate timing of end point measurements, the changing therapeutic environment, and the competitive trial system. We also review regulatory guidelines for end points and trial design and recommend ways to improve trial

Small bowel adenocarcinoma in patients with Crohn's disease compared with small bowel adenocarcinoma de novo.

International audienceBACKGROUND: Data concerning small bowel adenocarcinoma (SBA) in Crohn's disease (CD) come from case reports and small retrospective series. The aim of this study was to further describe SBA in patients with CD and compare it with SBA de novo. METHODS: Twenty patients with CD with SBA recruited in French university hospitals were studied and compared with 40 patients with SBA de novo recruited from a population-based registry. SBA occurred after a median time of 15 years of CD and was located within the inflamed areas of the ileum (n=19) or jejunum (n=1), whereas in patients with SBA de novo, it was distributed all along the small intestine. Median age at diagnosis of SBA was 47 years (range, 33-72 yr) in patients with CD and 68 years (range, 41-95 yr) in those with SBA de novo. RESULTS: The cumulative risk of SBA, assessed in a subgroup of patients, was 0.2% and 2.2% after 10 and 25 years of ileal CD, respectively. SBA accounted for 25% and 45% of the risk of gastrointestinal carcinoma after 10 and 25 years of CD, respectively. Diagnosis was made preoperatively in 1/20 patients with CD and 22/40 patients with SBA de novo. Signet ring cells were found in 35% of patients with CD but not in patients with SBA de novo. Relative survival was not significantly different in these 2 categories of patients (54 versus 37% and 35 versus 30% in patients with and without CD at 2 and 5 yr, respectively). CONCLUSIONS: SBA in CD is different from SBA de novo. It arises from longstanding ileal inflammation and is difficult to diagnose. SBA cumulative risk increases after 10 years of CD and is likely to cause premature mortality in patients with early-onset CD

Lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease: a prospective observational cohort study.

International audienceBACKGROUND: Reports of an increased risk of lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease are controversial. We assessed this risk in a prospective observational cohort study. METHODS: 19,486 patients with inflammatory bowel disease, of whom 11,759 (60.3%) had Crohn's disease and 7727 (39.7%) had ulcerative colitis or unclassified inflammatory bowel disease, were enrolled in a nationwide French cohort by 680 gastroenterologists, who reported details of immunosuppressive therapy during the observation period, cases of cancer, and deaths. The risk of lymphoproliferative disorder was assessed according to thiopurine exposure. Median follow-up was 35 months (IQR 29-40). FINDINGS: At baseline, 5867 (30.1%) of patients were receiving, 2809 (14.4%) had discontinued, and 10,810 (55.5%) had never received thiopurines. 23 new cases of lymphoproliferative disorder were diagnosed, consisting of one case of Hodgkin's lymphoma and 22 cases of non-Hodgkin lymphoproliferative disorder. The incidence rates of lymphoproliferative disorder were 0.90 per 1000 (95% CI 0.50-1.49) patient-years in those receiving, 0.20/1000 (0.02-0.72) patient-years in those who had discontinued, and 0.26/1000 (0.10-0.57) patient-years in those who had never received thiopurines (p=0.0054). The multivariate-adjusted hazard ratio of lymphoproliferative disorder between patients receiving thiopurines and those who had never received the drugs was 5.28 (2.01-13.9, p=0.0007). Most cases associated with thiopurine exposure matched the pathological range of post-transplant disease. INTERPRETATION: Patients receiving thiopurines for inflammatory bowel disease have an increased risk of developing lymphoproliferative disorders. FUNDING: Programme Hospitalier de Recherche Clinique National (AOM05157), Association François Aupetit, Délégation Inter-régionale de la Recherche clinique Ile de France-Assistance Publique Hôpitaux de Paris (AP-HP), Ligue contre le Cancer, and Fonds de Recherche de la Société Nationale Française de Gastro-entérologie