Mathurin Fumery

Natural history of elderly-onset inflammatory bowel disease: a population-based cohort study

Data on the natural history of elderly-onset inflammatory bowel disease (IBD) are scarce. Methods In a French population-based cohort we identified 841 IBD patients >60 years of age at diagnosis from 1988 to 2006, including 367 Crohns disease (CD) and 472 ulcerative colitis (UC). Results Median age at diagnosis was similar for CD (70 years (IQR: 65–76)) and UC (69 years (64–74)). Median follow-up was 6 years (2–11) for both diseases. At diagnosis, in CD, pure colonic disease (65%) and inflammatory behaviour (78%) were the most frequent phenotype. At maximal follow-up digestive extension and complicated behaviour occurred in 8% and 9%, respectively. In UC, 29% of patients had proctitis, 45% left-sided and 26% extensive colitis without extension during follow-up in 84%. In CD cumulative probabilities of receiving corticosteroids (CSs), immunosuppressants (ISs) and anti tumor necrosis factor therapy were respectively 47%, 27% and 9% at 10 years. In UC cumulative probabilities of receiving CS and IS were 40% and 15%, respectively at 10 years. Cumulative probabilities of surgery at 1 year and 10 years were 18% and 32%, respectively in CD and 4% and 8%, respectively in UC. In CD complicated behaviour at diagnosis (HR: 2.6; 95% CI 1.5 to 4.6) was associated with an increased risk for surgery while CS was associated with a decreased risk (HR: 0.5; 0.3 to 0.8). In UC CS was associated with an increased risk (HR: 2.2; 1.1 to 4.6) for colectomy. Conclusions Clinical course is mild in elderly-onset IBD patients. This information would need to be taken into account by physicians when therapeutic strategies are established.

Epidemiology of inflammatory bowel diseases: New insights from a French population-based registry (EPIMAD)

Most data regarding the natural history of inflammatory bowel diseases and their therapeutic management are from tertiary referral-centres. However, the patients followed in these centres represent a selected sample and extrapolation of these data to the general population is disputable. The EPIMAD Registry covers a large area of Northern France with almost 6 million inhabitants representing 9.3% of the entire French population. From 1988 to 2008, 18,170 incident patients were recorded in the registry including 8071 incident Crohns disease, 5113 incident ulcerative colitis and 591 unclassified inflammatory bowel disease cases. The aim of this study was to review some of the most recent information obtained from this large population-based registry since its launch in 1988.

Thromboembolic events and cardiovascular mortality in inflammatory bowel diseases: A meta-analysis of observational studies

OBJECTIVE Patients with inflammatory bowel disease (IBD) are at increased risk of having venous thromboembolism. The magnitude of this risk has yet to be determined. The question of whether IBD patients have an increased risk of arterial thromboembolism and cardiovascular (CV) mortality remains controversial. DESIGN We searched MEDLINE, Cochrane Library, EMBASE and international conference abstracts and included all controlled observational studies that evaluated the incidence of venous and/or arterial thromboembolic events (TE) and CV mortality in adult IBD. RESULTS 33 studies enrolling 207,814 IBD patients and 5,774,898 controls and capturing 3,253,639 hospitalizations of IBD patients and 936,411,223 hospitalizations of controls reported a risk of arterial and/or venous TE or CV mortality were included. The risk of venous TE was increased in IBD patients compared to the general population (RR, 1.96; 95% CI, 1.67-2.30) contrary to the risk of arterial TE (RR, 1.15; 95% CI, 0.91-1.45). There was an increased risk of deep venous thrombosis (RR, 2.42; 95% CI, 1.78-3.30), pulmonary embolism (RR, 2.53; 95% CI, 1.95-3.28), ischemic heart disease (RR, 1.35; 95% CI, 1.19-1.52) and mesenteric ischemia (RR, 3.46; 95% CI, 1.78-6.71). Differences in methodology were great between studies resulting in a significant heterogeneity in all previous analysis. CV mortality in IBD patients was not increased compared to the general population (SMR, 1.03; 95% CI, 0.93-1.14). CONCLUSION The risk of TE is increased in patients with IBD. This difference is mainly due to an increased risk of venous TE. There is no increased risk of arterial TE or CV mortality in IBD patients, but an increased risk of both ischemic heart disease and mesenteric ischemia.

Systematic review: fertility in non-surgically treated inflammatory bowel disease.

Inflammatory bowel diseases (IBD) typically affect young patients during the reproductive years, and reproductive issues are of key concern to them.

Methotrexate Is Not Superior to Placebo for Inducing Steroid-Free Remission, but Induces Steroid-Free Clinical Remission in a Larger Proportion of Patients With Ulcerative Colitis.

BACKGROUND & AIMS Parenteral methotrexate is an effective treatment for patients with Crohns disease, but has never been adequately evaluated in patients with ulcerative colitis (UC). We conducted a randomized controlled trial to determine its safety and efficacy in patients with steroid-dependent UC. METHODS We performed a double-blind, placebo-controlled trial to evaluate the efficacy of parenteral methotrexate (25 mg/wk) in 111 patients with corticosteroid-dependent UC at 26 medical centers in Europe from 2007 through 2013. Patients were given prednisone (10 to 40 mg/d) when the study began and were randomly assigned to groups (1:1) given placebo or methotrexate (intramuscularly or subcutaneously, 25 mg weekly) for 24 weeks. The primary end point was steroid-free remission (defined as a Mayo score ≤2 with no item >1 and complete withdrawal of steroids) at week 16. Secondary endpoints included clinical remission (defined as a Mayo clinical subscore ≤2 with no item >1) and endoscopic healing without steroids at weeks 16 and/or 24, remission without steroids at week 24, and remission at both weeks 16 and 24. RESULTS Steroid-free remission at week 16 was achieved by 19 of 60 patients given methotrexate (31.7%) and 10 of 51 patients given placebo (19.6%)--a difference of 12.1% (95% confidence interval [CI]: -4.0% to 28.1%; P = .15). The proportion of patients in steroid-free clinical remission at week 16 was 41.7% in the methotrexate group and 23.5% in the placebo group, for a difference of 18.1% (95% CI: 1.1% to 35.2%; P = .04). The proportions of patients with steroid-free endoscopic healing at week 16 were 35% in the methotrexate group and 25.5% in the placebo group--a difference of 9.5% (95% CI: -7.5% to 26.5%; P = .28). No differences were observed in other secondary end points. More patients receiving placebo discontinued the study because of adverse events (47.1%), mostly caused by UC, than patients receiving methotrexate (26.7%; P = .03). A higher proportion of patients in the methotrexate group had nausea and vomiting (21.7%) than in the placebo group (3.9%; P = .006). CONCLUSIONS In a randomized controlled trial, parenteral methotrexate was not superior to placebo for induction of steroid-free remission in patients with UC. However, methotrexate induced clinical remission without steroids in a significantly larger percentage of patients, resulting in fewer withdrawals from therapy due to active UC. ClinicalTrials.gov ID NCT00498589.

Long-term outcome after first intestinal resection in pediatric-onset Crohn's disease: a population-based study.

Background:To describe long-term postoperative evolution of pediatric-onset Crohns disease (CD) and identify predictors of outcome we studied a population-based cohort (1988–2004) of 404 patients (0–17 years), of which 130 underwent surgery. Methods:Risks for a second resection and first need for immunosuppressors (IS) and/or biologics were estimated by survival analysis and Cox models used to determine predictors of outcome. Impact of time of first surgery on nutritional catch-up was studied using regression. Results:In all, 130 patients (70 females) with a median age at diagnosis of 14.2 years (interquartile range: 12–16) were followed for 13 years (9.4–16.6). Probability of a second resection was 8%, 17%, and 29% at 2, 5, and 10 years, respectively. In multivariate analysis, age <14, stenosing (B2) and penetrating (B3) behaviors and upper gastrointestinal location (L4) at diagnosis were associated with an increased risk of second resection. Probability of receiving IS or biologics was 18%, 34%, and 47% at 2, 5, and 10 years, respectively. In multivariate analysis, L4 was a risk factor for requiring IS or biologics, while surgery within 3 years after CD diagnosis was protective. Catch-up in height and weight was better in patients who underwent surgery within 3 years after CD diagnosis than those operated on later. Conclusions:In this pediatric-onset CD study, mostly performed in a prebiologic era, a first surgery performed within 3 years after CD diagnosis was associated with a reduced need for IS and biologics and a better catch-up in height and weight compared to later surgery.

Mortality and cancer in pediatric-onset inflammatory bowel disease: a population-based study.

OBJECTIVES:Although the incidence of pediatric inflammatory bowel disease (IBD) continues to rise in Northern France, the risks of death and cancer in this population have not been characterized.METHODS:All patients <17 years, recorded in EPIMAD registry, and diagnosed between 1988 and 2004 with Crohns disease (CD) or ulcerative colitis (UC) were included. The observed incidences of death and cancer were compared with those expected in the regional general population obtained by French Statistical Institute (INSEE) and the cancer Registry from Lille. Comparisons were performed using Fishers exact test and were expressed using the standardized mortality ratios (SMRs) and standardized incidence ratios.RESULTS:A total of 698 patients (538 with CD and 160 with UC) were identified; 360 (52%) were men, the median age at IBD diagnosis was 14 years (12–16) and the median follow-up time was 11.5 years (7–15). During follow-up, the mortality rate was 0.84% (6/698) and did not differ from that in the reference population (SMR=1.4 (0.5–3.0); P=0.27). After a median follow-up of 15 years (10–17), 1.3% of patients (9/698) had a cancer: colon (n=2), biliary tract (cholangiocarcinoma; n=1), uterine cervix (n=1), prepuce (n=1), skin (basal cell carcinoma (n=2), hematological (acute leukemia; n=1), and small bowel carcinoid (n=1). There was a significantly increased risk of cancer regardless of gender and age (standardized incidence ratio=3.0 (1.3–5.9); P<0.02). Four out of nine patients who developed a cancer had received immunosuppressants or anti-tumor necrosis factor-α therapy (including combination therapy in three patients).CONCLUSIONS:In this large pediatric population-based IBD cohort, mortality did not differ from that of the general population but there was a significant threefold increased risk of neoplasia.

Validation of the Inflammatory Bowel Disease Disability Index in a population-based cohort

Background IBDs are chronic destructive disorders that negatively affect the functional status of patients. Recently, the Inflammatory Bowel Disease Disability Index (IBD-DI) was developed according to standard WHO processes. The aims of the current study were to validate the IBD-DI in an independent patient cohort, to develop an index-specific scoring system and to describe the disability status of a well-defined population-based cohort of French patients with IBD. Methods From February 2012 to March 2014, the IBD-DI questionnaire was administered to a random sample of adult patients with an established diagnosis of IBD issued from a French population-based registry. The IBD-DI consists of 28 items that evaluate the four domains of body functions, activity participation, body structures and environmental factors. Validation included item reduction and data structure, construct validity, internal consistency, interobserver and intraobserver reliability evaluations. Results 150 patients with Crohns disease (CD) and 50 patients with UC completed the IBD-DI validation phase. The intraclass correlation coefficient for interobserver reliability was 0.91 and 0.54 for intraobserver reliability. Cronbachs α of internal consistency was 0.86. IBD-DI scores varied from 0 to 100 with a mean of 35.3 (Q1=19.6; Q3=51.8). IBD-DI scores were highly correlated with Inflammatory Bowel Disease Questionnaire (−0.82; p<0.001) and SF-36 (–0.61; p<0.05) scores. Female gender (p<0.001), clinical disease activity (p<0.0001) and disease duration (p=0.02) were associated with higher IBD-DI scores. Conclusions The IBD-DI has been validated for use in clinical trials and epidemiological studies. The IBD-DI showed high internal consistency, interobserver reliability and construct validity, and a moderate intraobserver reliability. It comprises 14 questions and ranges from 0 to 100. The mean IBD-DI score was 35.3 and was associated with gender, clinical disease activity and disease duration. Further research is needed to confirm the structural validity and to assess the responsiveness of IBD-DI. Trial registration number 2011-A00877-34

Efficacy of adalimumab in patients with Crohn's disease and symptomatic small bowel stricture: a multicentre, prospective, observational cohort (CREOLE) study

Objective The efficacy of anti-tumour necrosis factors (anti-TNFs) in patients with Crohns disease (CD) and symptomatic small bowel stricture (SSBS) is controversial. The aim of this study was to estimate the efficacy of adalimumab in these patients and to identify the factors predicting success. Design We performed a multicentre, prospective, observational cohort study in patients with CD and SSBS. The included patients underwent magnetic resonance enterography at baseline and subsequently received adalimumab. The primary endpoint was success at week 24, defined as adalimumab continuation without prohibited treatment (corticosteroids after the eight week following inclusion, other anti-TNFs), endoscopic dilation or bowel resection. The baseline factors independently associated with success were identified using a logistic regression model, leading to a simple prognostic score. Secondary endpoints were prolonged success after week 24 (still on adalimumab, without dilation nor surgery) and time to bowel resection in the whole cohort. Results From January 2010 to December 2011, 105 patients were screened and 97 were included. At week 24, 62/97 (64%) patients had achieved success. The prognostic score defined a good prognosis group with 43/49 successes, an intermediate prognosis group with 17/28 successes and a poor prognosis group with 1/16 successes. After a median follow-up time of 3.8 years, 45.7%±6.6% (proportion±SE) of patients who were in success at week 24 (ie, 29% of the whole cohort) were still in prolonged success at 4 years. Among the whole cohort, 50.7%±5.3% of patients did not undergo bowel resection 4 years after inclusion. Conclusions A successful response to adalimumab was observed in about two-thirds of CD patients with SSBS and was prolonged in nearly half of them till the end of follow-up. More than half of the patients were free of surgery 4 years after treatment initiation. Clinical Trial registration number NCT01183403; Results.

Incidence, Risk Factors, and Outcomes of Colorectal Cancer in Patients With Ulcerative Colitis With Low-Grade Dysplasia: A Systematic Review and Meta-analysis

Background & Aims Little is known about outcomes of patients with ulcerative colitis with low‐grade dysplasia (UC‐LGD). We estimated the incidence of and risk factors for progression to colorectal cancer (CRC) in cohorts of patients with UC‐LGD who underwent surveillance (surveillance cohort), and the prevalence of dysplasia‐related findings among patients who underwent colectomy for UC‐LGD (surgical cohort). Methods We performed a systematic literature review through June 1, 2016, to identify cohort studies of adults with UC‐LGD. We estimated pooled incidence rates of CRC and risk factors associated with dysplasia progression in surveillance cohorts, and prevalence of synchronous advanced neoplasia (CRC and/or high‐grade dysplasia) in surgical cohorts. Results In 14 surveillance cohort studies of 671 patients with UC‐LGD (52 developed CRC), the pooled annual incidence of CRC was 0.8% (95% confidence interval [CI], 0.4–1.3); the pooled annual incidence of advanced neoplasia was 1.8% (95% CI, 0.9–2.7). Risk of CRC was higher when LGD was diagnosed by expert gastrointestinal pathologist (1.5%) than by community pathologists (0.2%). Factors significantly associated with dysplasia progression were concomitant primary sclerosing cholangitis (odds ratio [OR], 3.4; 95% CI, 1.5–7.8), invisible dysplasia (vs visible dysplasia; OR, 1.9; 95% CI, 1.0–3.4), distal location (vs proximal location; OR, 2.0; 95% CI, 1.1–3.7), and multifocal dysplasia (vs unifocal dysplasia; OR, 3.5; 95% CI, 1.5–8.5). In 12 surgical cohort studies of 450 patients who underwent colectomy for UC‐LGD, 34 patients had synchronous CRC (pooled prevalence, 17%; 95% CI, 8–33). Conclusion In a systematic review of the literature, we found that among patients with UC‐LGD under surveillance, the annual incidence of progression to CRC was 0.8%; differences in rates of LGD diagnosis varied with pathologists’ level of expertise. Concomitant primary sclerosing cholangitis, invisible dysplasia, distal location, and multifocal LGD are high‐risk features associated with dysplasia progression.