Citations

SUMMARYBackgroundClinical factors were previously identified as predictors of short‐term treatment efficacy in Crohn's disease (CD). The PRECiSE 3 (P3) 7‐year trial provides an opportunity to study predictors of short‐ and long‐term clinical remission among CD patients treated with certolizumab pegol (CZP).AimTo identify factors that influence long‐term remission of CD with CZP treatment.MethodsPatients who had completed placebo‐controlled studies (PRECiSE 1/PRECiSE 2, P1/P2) enrolled in P3 and received open‐label CZP 400 mg every 4 weeks up to 7 years. Baseline predictors included, but were not limited to, smoking status, disease duration, prior inflammatory bowel disease (IBD) surgery, Harvey–Bradshaw Index (HBI), albumin, haematocrit and CZP exposure; association with time to initial remission (HBI ≤4) was tested for patients who received CZP in P1/P2; time to loss of remission/frequency of maintenance of remission was also tested. Univariate analyses and multivariate Cox or logistic regression models were used.ResultsPredictors for initial remission (N = 377) included age, haematocrit, prior IBD surgery and entry HBI (P < 0.05 for all). Predictors for loss of remission (N = 437) included HBI, serum albumin concentration, haematocrit, smoking status and exposure. Predictors of maintenance of remission (N = 437) included haematocrit, IBD surgery, HBI, disease duration, serum albumin concentration and exposure. Significant predictors were confirmed with stepwise multivariate regression models.ConclusionsThese analyses identified several influential parameters for short‐and long‐term remission of Crohn's disease with certolizumab pegol treatment. The data yield valuable hypotheses regarding factors that influence certolizumab pegol treatment. More investigation is needed.(ClinicalTrials.gov identifier NCT00552058).

SummaryBackgroundChronic ulcerative colitis (CUC) and colonic Crohn's disease (CD) increase colorectal neoplasia (CRN) risk. While sessile serrated polyp (SSP) is a known cancer precursor, serrated epithelial changes (SEC) are of uncertain prevalence and neoplastic risk.AimTo assess the serrated lesion detection rates in CUC and CD and documented incidence of subsequent CRN in a retrospective, single‐centre cohort study.MethodsPatients were identified by a central diagnostic index and pathology review confirmed SEC, SSP, CUC and CD diagnoses from 2006–12. Matched controls were identified from among all CUC and CD patients having colonoscopy during the second half of the time period. All were followed for incident CRN, estimated by the Kaplan–Meier method.ResultsBetween 2006 and 2012, 79 SEC and 10 SSP cases were identified. Detection rates were estimated to be 10/1000 and 2/1000 patients, for SEC and SSP respectively, among 4208 unique CUC or CD patients having colonoscopy from 2010–12. With only 10 cases, SSP patients were not further analysed. Cumulative incidence of subsequent CRN at 1 and 3 years was 12% (95% CI, 0–30%) and 30% (3–57%), respectively, in SEC patients compared to 4% (0–12%) and 9% (0–23%), respectively, in CUC or CD controls (P = 0.047, log‐rank). However, this statistical difference was not significant after patients were stratified for history of prior or synchronous dysplasia (P = 0.09).ConclusionsSerrated epithelial changes and sessile serrated polyps are uncommonly detected by colonoscopy in chronic ulcerative colitis and Crohn's disease patients. Histology with changes of serrated epithelium may be associated with risk of subsequent colorectal neoplasia, however further studies are needed to explore this relationship.

Summary Background Serological markers such as anti‐neutrophil cytoplasmic antibody ( ANCA ) and anti‐ S accharomyces cerevisiae antibody ( ASCA ) may be associated with pouchitis after ileal pouch‐anal anastomosis ( IPAA ). Aim To perform a systematic review with meta‐analysis of studies evaluating the association of ANCA and ASCA status with risk of acute and chronic pouchitis after IPAA . Methods We searched multiple databases (upto S eptember 2012) for studies reporting ANCA and/or ASCA status along with risk of acute or chronic pouchitis after IPAA in adults with ulcerative colitis ( UC ). We abstracted odds ratio ( OR ) or raw data from the individual studies to calculate summary OR estimates with 95% CI s using random‐effects model. Results Eight studies reporting 184 cases of acute pouchitis and six studies reporting 151 cases of chronic pouchitis were included. The odds of chronic pouchitis were 76% higher in ANCA ‐positive patients than ANCA ‐negative (six studies; OR : 1.76; 95% CI : 1.19–2.61; P < 0.01). ASCA‐positivity was not associated with the risk of chronic pouchitis (three studies; OR : 0.89; 95% CI : 0.49–1.59; P = 0.68). Neither ANCA (eight studies; OR : 1.54; 95% CI : 0.79–3.02; P = 0.21) nor ASCA ‐positivity (two studies; OR : 1.28; 95% CI : 0.25–6.54; P = 0.77) were associated with the risk of acute pouchitis. Conclusions The risk of chronic pouchitis after IPAA is higher in ANCA ‐positive patients, but the risk of acute pouchitis is unaffected by ANCA status. ASCA status was not associated with the risk of acute or chronic pouchitis. This information may be used to counsel UC patients regarding their risk of pouchitis after IPAA .

SummaryBackgroundCurrent approaches to the detection of colorectal neoplasia associated with inflammatory bowel disease (IBD‐CRN) are suboptimal.AimTo test the feasibility of using stool assay of exfoliated DNA markers to detect IBD‐CRN.MethodsThis investigation comprised tissue and stool studies. In the tissue study, gene sequencing and methylation assays were performed on candidate genes using tissue DNA from 25 IBD‐CRNs and from 25 IBD mucosae without CRN. Mutations on p53, APC, KRAS, BRAF or PIK3CA genes were insufficiently informative, but several aberrantly methylated genes were highly discriminant. In the stool study, we evaluated candidate methylated genes (vimentin, EYA4, BMP3, NDRG4) in a prospective blinded study on buffered stools from 19 cases with known IBD‐CRN and 35 age‐ and sex‐matched IBD controls without CRN. From stool‐extracted DNA, target genes were assayed using quantitative allele‐specific real‐time target and signal amplification method.ResultsIBD‐CRN cases included 17 with ulcerative colitis (UC) and two with Crohn's disease (CD); nine had cancer and 10 had dysplasia. Controls included 25 with UC and 10 with CD. Individually, BMP3, vimentin, EYA4 and NDRG4 markers showed high discrimination in stools with respective areas under the ROC curve of 0.91, 0.91, 0.85 and 0.84 for total IBD‐CRN and of 0.97, 0.97, 0.95 and 0.85 for cancer. At 89% specificity, the combination of BMP3 and mNDRG4 detected 9/9 (100%) of CRC and 80% of dysplasia, 4/4 (100%) of high grade and 4/6 (67%) of low grade.ConclusionThese findings demonstrate the feasibility of stool DNA testing for non‐invasive detection of colorectal neoplasia associated with inflammatory bowel disease.

The changing epidemiology of inflammatory bowel disease (IBD) across time and geography suggests that environmental factors play a major role in modifying disease expression. Disease emergence in developing nations suggests that epidemiological evolution is related to westernisation of lifestyle and industrialisation. The strongest environmental associations identified are cigarette smoking and appendectomy, although neither alone explains the variation in incidence of IBD worldwide. Urbanisation of societies, associated with changes in diet, antibiotic use, hygiene status, microbial exposures and pollution have been implicated as potential environmental risk factors for IBD. Changes in socioeconomic status might occur differently in different geographical areas and populations and, consequently, it is important to consider the heterogeneity of risk factors applicable to the individual patient. Environmental risk factors of individual, familial, community-based, country-based and regionally based origin may all contribute to the pathogenesis of IBD. The geographical variation of IBD provides clues for researchers to investigate possible environmental aetiological factors. The present review aims to provide an update of the literature exploring geographical variability in IBD and to explore the environmental risk factors that may account for this variability.

SummaryBackgroundUlcerative colitis (UC) and Crohn's disease can sometimes relapse and be refractory to standard treatment following orthotopic liver transplantation (OLT) despite post‐transplantation immunosuppressive therapy.AimTo evaluate the efficacy and safety of anti‐tumour necrosis factor (anti‐TNF) agents for the management of IBD following OLT.MethodsWe reviewed the records of patients with a diagnosis of IBD who underwent OLT at Mayo Clinic Rochester between 1985 and 2009. Patients were included if they had received anti‐TNF therapy post‐OLT. Clinical response was defined as a physician's assessment of improvement after 12 weeks of anti‐TNF usage, and mucosal healing was defined as the absence of ulcerations on follow‐up endoscopy.ResultsThe median age of the eight study patients was 42.0 years and 37.5% were female patients. All had been diagnosed with IBD prior to OLT (UC in three and Crohn's disease in five). Indication for OLT was cirrhotic stage primary sclerosing cholangitis (PSC), and three concomitantly had cholangiocarcinoma. Clinical response was demonstrated in seven of eight patients (87.5%) and mucosal healing was demonstrated in three of seven (42.9%). Four infections (oral candidiasis, Clostridium difficile colitis, bacterial pneumonia and cryptosporidiosis) in three patients were reported. One patient developed an Epstein–Barr virus‐positive post‐transplant lympho‐proliferative disorder. One death occurred due to complications from recurrent PSC.ConclusionsStarting Anti‐TNF therapy following orthotopic liver transplantation appears to be a potential option for inflammatory bowel disease management. Additional studies are needed, however, to confirm these findings and to further assess risks associated with this treatment strategy.