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Background: Sulfasalazine is accepted therapy for active ulcerative colitis, but side-effects and intolerance are common. Balsalazide is an azo-bonded pro-drug which also releases 5-aminosalicylic acid into the colon, but uses an inert carrier molecule. Aim: To compare the safety and efficacy of sul- fasalazine, 3 g, with balsalazide, 6.75 g, in the initial daily treatment of mild to moderate ulcerative colitis. Methods: A randomized, multicentre, double-blind, parallel group study was performed, with a treatment duration of 8 weeks. Patients on previous maintenance treatment were excluded. The trial medication was the sole treatment for the colitis. Efficacy was assessed by patient diaries, symptom assessment, sigmoidoscopic appearance and histology. Results: Fifty patients were recruited: 26 allocated to the balsalazide group and 24 to the sulfasalazine group. More patients withdrew due to adverse events in the sulfasalazine group (nine patients vs. one patient in the balsalazide group, P=0.004). Improvement occurred in both groups, with a tendency to a faster response with balsalazide. Of the patients taking balsalazide, 61% achieved clinical and sigmoidoscopic remission. Conclusions: Balsalazide, 6.75 g, is effective as the sole treatment for patients with mild to moderately active ulcerative colitis, with significantly fewer withdrawals due to side-effects than in a similar group of patients taking sulfasalazine, 3 g.

Background: Sulfasalazine is well established in the treatment of active ulcerative colitis. Intolerance to sulfasalazine, however, is a common problem. Balsalazide has been designed to deliver 5-aminosalicylic acid to the colon without the poor tolerability of sulfasalazine. Aim: To compare the safety and efficacy of balsalazide, 6.75 g daily, with sulfasalazine, 3 g daily, in the treatment of active ulcerative colitis of all grades of severity. Methods: Balsalazide and sulfasalazine were compared in a multicentre, double-blind, parallel group study over 12 weeks. Patients were stratified for disease severity and topical and/or oral steroids were co-administered where clinically necessary. Results: Fifty-seven patients were randomized: 28 to receive balsalazide and 29 to receive sulfasalazine. Significantly fewer patients withdrew from the balsalazide group due to adverse events (2/28 vs. 9/29, P=0.041). These data confirm that balsalazide is better tolerated than sulfasalazine. In patients able to tolerate the treatment, similar improvements were recorded in clinical, sigmoidoscopic and histological assessments in both treatment groups. Conclusions: This study confirms the better tolerability of balsalazide compared to sulfasalazine, and supports the use of balsalazide in ulcerative colitis of all grades of severity.

Lymphoma complicating inflammatory bowel disease is well described. Whether the risk of lymphoma is incre- ased by immunosuppressive treatment with azathiop- rine, 6-mercaptopurine or infliximab is a common concern among patients and physicians considering using these agents. This review aims to quantify the lymphoma risk in inflammatory bowel disease and the added risk attributable to these treatments. The evidence from published cases is that lymphomas occur at sites of active inflammatory bowel disease more often than expected for this to be a chance association. Studies on inflammatory bowel disease populations are conflicting, with some follow-up studies from large inflammatory bowel disease clinics showing an increase in lymphoma incidence, while other population-based studies show little or no increase in risk of lymphoma. A small increase in lymphoma risk in inflammatory bowel disease, perhaps 2–3-fold, may be compatible with both sets of data. Studies of the risks associated with immuno- suppression are less satisfactory, with smaller numbers of patients and relatively short follow-up. The available evidence would support a further increase in lymphoma risk associated with immunosuppressive treatment in inflammatory bowel disease of around fivefold compared to no immunosuppressive use, and tenfold compared to the general population. The risks appear to be less than that associated with renal and hepatic transplant-related immunosuppression. Infliximab treatment is still too new to make a full assessment of its long-term safety, but post-marketing surveillance currently suggests that lymphoma risk may not be any greater than that associated with azathioprine and 6-mercaptopurine. Population-wide surveillance for lymphoma in inflammatory bowel disease would be required to narrow the confidence intervals on these estimates of lymphoma risk in inflammatory bowel disease and immunosuppressive treatment.

Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal tract of unknown aetiology, phenotypically categorized into ulcerative colitis (UC) and Crohn disease (CD). Genetic factors are of considerable importance in both. The genetic relationship between IBD and the interleukin-1 receptor antagonist and interleukin-1beta genes (IL-1RN, and IL-1B, respectively) has been extensively studied. However, the quality and outcome of the genetic association studies, in particular the association with IL-1RN*2, have been variable and these associations remain controversial. The aim of the present study was to re-investigate these two candidate genes in a large series of IBD patients from a genetically homogeneous population with low levels of population admixture, and provide a definitive answer to this question.A total of 529 northern European Caucasoid patients with IBD (347 UC, 182 CD) and 289 racially and geographically matched healthy controls were studied. The IL-1RN and IL-1B genotypes, allele frequencies and most probable haplotypes were determined by standard PCR protocols.There were no significant differences in the distributions of the IL-1RN and IL-1B genotypes, allele frequencies or haplotypes in either patient series compared to healthy controls or between clinical subsets. Genotype distribution and frequency data for allele 2 (IL-1RN*2) in particular showed no significant differences across all patient groups for all three series.The findings of this study lead us to reject the IL-1RN*2 association with IBD.

Interleukin-10 (IL-10) has a key role in regulating mucosal inflammation. The role of functional polymorphisms at positions -627 and -1117 in the IL-10 gene as candidate susceptibility loci in inflammatory bowel disease and their importance in determining disease extent were evaluated in 159 patients with ulcerative colitis (83 left-sided; 76 extensive), 90 patients with Crohn's disease (22 small bowel; 29 large bowel; 39 both), and 227 controls. Genotyping was performed either by PCR-RFLP assays (-627 site) or SSCP analysis (-1117 site). An excess of -627A allele was observed in patients with left-sided colitis (52%) compared with controls (33%; P = 0.004) suggesting that IL-10 may influence the extent of the disease. These results were not replicated in a newly recruited group (N = 100) of patients with UC. We conclude that polymorphisms at -627 and -1117 sites in the IL-10 gene do not contribute to the susceptibility to IBD or determining the extent of the disease in our population.

A genome- wide association scan in individuals with Crohn's disease by the Wellcome Trust Case Control Consortium detected strong association at four novel loci. We tested 37 SNPs from these and other loci for association in an independent case- control sample. We obtained replication for the autophagy- inducing IRGM gene on chromosome 5q33.1 ( replication P = 6.6 x 10(-4), combined P = 2.1 x 10(-10)) and for nine other loci, including NKX2- 3, PTPN2 and gene deserts on chromosomes 1q and 5p13.

Carcinoma is a recognized but rare complication of small bowel Crohn's disease. This case series emphasizes the importance of considering this diagnosis in patients with small bowel Crohn's disease. We report three cases in which patients were treated for presumed exacerbations of Crohn's, but were subsequently found to have underlying small bowel adenocarcinoma. This case series will demonstrate the need for the surgical assessment of patients with long-standing symptomatic Crohn's disease that fails to settle with conservative management.

The pathogenesis of inflammatory bowel disease (IBD) remains incompletely understood, but is thought to be a consequence of immune dysregulation, impaired mucosal integrity, enteric bacterial dysbiosis and genetic susceptibility factors. Recent drug advances in the treatment of IBD have clarified the role of existing medication, including 5-amino-salicylic acids (5-ASAs) and has seen a burgeoning use of treatment with biologicals. With recent advances in our understanding of these debilitating diseases, it is hoped that novel therapeutic targets can be identified.

A search for variants in coding exons of 25 genome-wide association study risk genes in a large cohort of autoimmune patients finds that rare coding-region variants at known loci have a negligible role in common autoimmune disease susceptibility, arguing against the previously proposed rare-variant synthetic genome-wide association hypothesis. Although many common variants of modest-effect size have been identified in genome-wide association studies (GWAS), much of the heritability of complex traits remains unexplained. These authors looked for variants in coding exons of 25 GWAS risk genes in a large cohort of subjects with six autoimmune disease phenotypes and controls, and show that rare coding-region variants at known loci have at most a minor role in common autoimmune disease susceptibility. These results do not support the theory that the missing heritability for common autoimmune diseases is attributable to rare coding mutations at known loci, but are consistent with disease caused by many common-variant loci of weak effect. Genome-wide association studies (GWAS) have identified common variants of modest-effect size at hundreds of loci for common autoimmune diseases; however, a substantial fraction of heritability remains unexplained, to which rare variants may contribute1,2. To discover rare variants and test them for association with a phenotype, most studies re-sequence a small initial sample size and then genotype the discovered variants in a larger sample set3,4,5. This approach fails to analyse a large fraction of the rare variants present in the entire sample set. Here we perform simultaneous amplicon-sequencing-based variant discovery and genotyping for coding exons of 25 GWAS risk genes in 41,911 UK residents of white European origin, comprising 24,892 subjects with six autoimmune disease phenotypes and 17,019 controls, and show that rare coding-region variants at known loci have a negligible role in common autoimmune disease susceptibility. These results do not support the rare-variant synthetic genome-wide-association hypothesis6 (in which unobserved rare causal variants lead to association detected at common tag variants). Many known autoimmune disease risk loci contain multiple, independently associated, common and low-frequency variants, and so genes at these loci are a priori stronger candidates for harbouring rare coding-region variants than other genes. Our data indicate that the missing heritability for common autoimmune diseases may not be attributable to the rare coding-region variant portion of the allelic spectrum, but perhaps, as others have proposed, may be a result of many common-variant loci of weak effect7,8,9,10.

Purpose: A procedure was designed to correct vesicoureteral reflux with minimally invasive technology.Materials and Methods: A total of 22 children 14 months to 18 years old underwent percutaneous endoscopic trigonoplasty between January and June 1995. Followup ranges from 4 to 11 months. In 32 ureters reflux was grade 2 in 13, grade 3 in 13, grade 4 in 5 and grade 5 in 1.Results: All patients had normal sonography of the kidneys after surgery. On followup voiding cystourethrography at 2 or 6 months there was resolution of reflux in 20 of the 32 ureters (62.5 percent). The probability of resolution was unrelated to patient age, laterality of reflux, initial grade, operative sequence or preoperative bladder instability. The 3 major complications were vesicovaginal fistula, hypnotremia and perivesical fluid collection.Conclusions: Percutaneous endoscopic trigonoplasty is technically feasible but it involves a distinct learning curve. It offers significant advantages related to more rapid recovery wi...

The ideal imaging method in inflammatory bowel disease would reliably detect inflammation, identify the correct intestinal location, and assess the severity of the disease. The aim of this study was to compare scintigraphic methods of quantifying overall disease activity using both indium-111 (111In) and technetium-99M (99mTc) HMPAO labelled leucocyte scans. The four day faecal excretion of 111In was measured after 111In scintigraphy in 24 patients known to have inflammatory bowel disease. The same patients also underwent 99mTc HMPAO scanning. The scans were performed 10 days or less apart with no changes in treatment between scans. Bowel activity on the 99mTc HMPAO scans was assessed using a computer based method (scan score) and a visual grading method in a further 54 99mTc HMPAO. The results showed a close correlation between inflammatory activity defined by faecal 111In excretion and the scan score generated from the computer analysis of the 99mTc HMPAO image (Spearman rank correlation: rs = 0.78; p < 0.001). Accurate information to localise inflammatory activity could be obtained by simple visual assessment of both types of scan images, although image quality was superior with 99mTc HMPAO. Qualification of disease activity from 99mTc HMPAO images by visual grading was associated with a large variability, only 69% of scans had similar scores when graded by three observers. Computer generated image analysis was more reproducible. In conclusion, in inflammatory bowel disease 99mTc HMPAO scintigraphy and faecal 111In excretion correlated well. Either method can quantify and localise the inflammation. As 99mTc HMPAO scanning provides a quicker result, with a lower radiation dose, and avoids faecal collection, it may be the preferred method.

Elemental diets are effective in inducing remission in active Crohn's disease, but how they exert this therapeutic effect is unclear. In a previous study a whole protein containing diet proved less effective than one in which food antigens were excluded, suggesting that exclusion of food antigens from the gut was a possible mechanism. This study was designed to test whether an oligopeptide diet of hydrolysed proteins was as effective as an amino acid based diet. These diets were equally antigen free but with different nitrogen sources. Forty four patients with active Crohn's disease were randomised in a controlled trial of amino acid versus oligopeptide diet. The feeds were given by nasogastric tube in equicaloric quantities and were the sole form of nutrition. Treatment was continued for four weeks although failure to improve by day 10 resulted in withdrawal. Quantitative leucocyte scintigraphy was used to investigate the effect of diet treatment on gut inflammation. Clinical and nutritional responses to treatment were also measured. Sixteen patients entered remission (including withdrawal of corticosteroids), six patients could not tolerate the nasogastric tube, and 22 patients failed to respond. The two diets were equally effective. Patients who responded had a rapid drop in clinical index of disease activity and a major reduction in the bowel uptake of leucocytes on scintigraphy. The oligopeptide and amino acid based enteral feeds were equally effective at inducing remission in active Crohn's disease. With both diets clinical improvement was accompanied by a reduction in intestinal inflammation.

Objective Etrolizumab (rhuMAb β7, anti-β7, PRO145223) is a humanised monoclonal antibody targeting the β7 subunit of the heterodimeric integrins α4β7 and αEβ7, which are implicated in leucocyte migration and retention in ulcerative colitis (UC). This randomised phase I study evaluated the safety and pharmacology of etrolizumab in patients with moderate to severe UC. Design In the single ascending dose (SAD) stage, etrolizumab (0.3, 1.0, 3.0, 10 mg/kg intravenous, 3.0 mg/kg subcutaneous (SC) or placebo) was administered 4:1 (n=25) in each cohort. In the multiple dose (MD) stage, new patients received monthly etrolizumab (0.5 mg/kg SC (n=4), 1.5 mg/kg SC (n=5), 3.0 mg/kg SC (n=4), 4.0 mg/kg intravenous (n=5)) or placebo (n=5). The pharmacokinetics was studied and Mayo Clinic Score evaluated at baseline, day 29 (SAD), and days 43 and 71 (MD). Results In the SAD stage, there were no dose limiting toxicities, infusion or injection site reactions. Two impaired wound healing serious adverse events occurred in two patients receiving etrolizumab. In the MD stage, there were no dose limiting toxicities, and no infusion or injection site reactions. Headache was the most common adverse event, occurring more often in etrolizumab patients. Antietrolizumab antibodies were detected in two subjects. The duration of β7 receptor full occupancy was dose related. A clinical response was observed in 12/18 patients, and clinical remission in 3/18 patients treated with etrolizumab in the MD stage, compared with 4/5 and 1/5 placebo patients, respectively. Conclusion Etrolizumab is well tolerated in moderate to severe UC. Further investigation is warranted.

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 x 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. Combined with previously confirmed loci, these results identify 71 distinct loci with genome-wide significant evidence for association with Crohn's disease.

This is an introduction to the Gut tutorial ‘Management of Crohn's disease’ hosted on BMJ Learning—the best available learning website for medical professionals from the BMJ Group. This interactive module is focused around a case of Crohn's disease and its medical and surgical management over a period of …

Summary Background The detection of auto antibodies directed against tissue transglutaminase (anti-tTG antibodies) has a well-established role in the diagnosis of coeliac disease, but the value of these antibodies in long-term follow-up is controversial. Aims To determine if serial anti-tTG antibody measurements could confirm adherence to a gluten-free diet (GFD) and identify patients at risk of disease complications. Methods In a 54-month cohort follow-up study, 182 adult patients were assessed. Data recorded included self-assessment of GFD adherence; anti-tTG antibody concentration and serum ferritin, vitamin B12 and folate. Where available, bone mineral density (BMD) and duodenal histology data were retrieved. Results Persistently elevated anti-tTG antibody levels were significantly associated with abnormal duodenal histology (P 85% while the sensitivity was 39–60%. Anti-tTG antibody concentrations fell rapidly following successful initiation of a GFD, and maintenance of normalization identified those who continued to be adherent to the diet. Conclusions This study supports a strategy of using anti-tTG antibody concentrations to monitor newly diagnosed and established patients with coeliac disease, and to target dietetic intervention to reduce the risk of complication.

Background Identifying Crohn's disease recurrence in symptomatic patients after ileocaecal resection is difficult. The aim of this study was to evaluate faecal concentrations of granulocyte degradation products in this setting. Methods A postoperative cohort of 13 patients was followed prospectively for 1 year with regular faecal calprotectin (FC) and lactoferrin (FL) measurements. A second postoperative cohort (median 24 months after resection) of 104 patients provided a single stool sample. Faecal measurements were compared with symptom diaries, the Harvey Bradshaw Index, endoscopic examination, C-reactive protein and platelet measurement. Results In the uncomplicated course, both markers normalized within 2 months. Both FC and FL correlated significantly with Harvey Bradshaw Index (P < 0·001). Twenty-eight patients with severely clinically active disease had high mean(s.e.) levels of FC (661·1(119·1) µg/g) and FL (116·6(32·2) µg/g); and 43 with clinically inactive disease had low levels of FC (70·2(27·1) µg/g) and FL (5·9(2·4) µg/g). In patients with mild to moderately clinically active disease, FC and FL identified individuals with and without recurrent inflammatory disease. Faecal markers were more accurate at predicting clinical disease activity than C-reactive protein, platelet count or endoscopic appearance. Conclusion FC and FL are non-invasive tests that can help to identify disease recurrence in symptomatic postoperative patients.

We report results of a nonsynonymous SNP scan for ulcerative colitis and identify a previously unknown susceptibility locus at ECM1. We also show that several risk loci are common to ulcerative colitis and Crohn's disease (IL23R, IL12B, HLA, NKX2-3 and MST1), whereas autophagy genes ATG16L1 and IRGM, along with NOD2 (also known as CARD15), are specific for Crohn's disease. These data provide the first detailed illustration of the genetic relationship between these common inflammatory bowel diseases.

Background & Aims: Identification of inflammatory bowel disease (IBD) susceptibility genes is key to understanding pathogenic mechanisms. Recently, the North American IBD Genetics Consortium provided compelling evidence for an association between ileal Crohn’s disease (CD) and the IL23R gene using genome-wide association scanning. External replication is a priority, both to confirm this finding in other populations and to validate this new technique. We tested for association between IL23R and IBD in a large independent UK panel to determine the size of the effect and explore subphenotype correlation and interaction with CARD15. Methods: Eight single nucleotide polymorphism markers in IL23R tested in the North American study were genotyped in 1902 cases of Crohn’s disease (CD), 975 cases of ulcerative colitis (UC), and 1345 controls using MassARRAY. Data were analyzed using χ2 statistics, and subgroup association was sought. Results: A highly significant association with CD was observed, with the strongest signal at coding variant Arg381Gln (allele frequency, 2.5% in CD vs 6.2% in controls [P = 1.1 × 10−12]; odds ratio, 0.38; 95% confidence interval, 0.29–0.50). A weaker effect was seen in UC (allele frequency, 4.6%; odds ratio, 0.73; 95% confidence interval, 0.55–0.96). Analysis accounting for Arg381Gln suggested that other loci within IL23R also influence IBD susceptibility. Within CD, there were no subphenotype associations or evidence of interaction with CARD15. Conclusions: This study shows an association between IL23R and all subphenotypes of CD with a smaller effect on UC. This extends the findings of the North American study, providing clear evidence that genome-wide association scanning can successfully identify true complex disease genes.

Introduction Orofacial granulomatosis (OFG) is a rare, disfiguring inflammatory disorder of the mouth where a proportion of cases also have intestinal Crohn’s disease (CD). The aetiology remains largely unknown, although there is high prevalence of allergy in OFG with and without CD. Our objective was to investigate whether OFG and CD have shared genetic aetiology or whether OFG is mediated by distinct immune-related genetic susceptibility variants. Method Patients were clinically assessed and determined to either demonstrate isolated oral manifestations (OFG only) or concurrent intestinal CD (CD/OFG). Genomic DNA from 263 patients was genotyped using the Immunochip, a custom Illumina microarray assessing 196,524 genetic variants across multiple immune-related disease loci. Patient data was compared to data for 4,307 population controls from the UKIBD consortium. Statistical analysis was performed using PLINK, a whole genome association analysis program and the R statistical package. Results Analyses revealed two significant associations (p –6 ) within the OFG only cohort with single nucleotide polymorphisms (SNPs) on chromosome 11q13.5 near the LRRC32 gene (p = 1.6 × 10 –9 ) and on chromosome 6 (p = 3.9 × 10 –7 ) within the MHC class I region. The 11q13.5 locus has previously shown association with atopic conditions and the MHC class I region is implicated in numerous allergic and autoimmune diseases, including CD. In addition, a highly suggestive association was detected from the CD/OFG group on chromosome 5p13 (p = 2.5 × 10 –6 ), a known risk locus for CD. Collectively, these results suggest that OFG is influenced by common variants implicated in allergy and immunity, supporting the link between OFG and allergy. However there may also be some overlap with genetic aetiology for CD. Replication in a larger independent cohort is required to substantiate our findings. Conclusion OFG is likely to be a complex disease mediated by diverse genetic variants, sharing genetic susceptibility with allergic disorders and autoimmune conditions such as CD. Disclosure of interest None Declared.

Introduction A high fat (HF)/high sugar (HS), Western diet has been implicated in the pathogenesis of IBD. 1 The BA receptor, farnesoid-x receptor (FXR), is central to the crosstalk between the host and its microbiota. 2 FXR has an immuno-modulatory role in the GI tract. 3,4 We hypothesised that disruption to BA signalling, induced by a HF/HS diet associated dysbiosis, is a mechanism linking diet to the development of IBD. The aim of this study was to investigate the effect of HF/HS feeding and FXR agonism on ileal inflammation in a mouse model of obesity. Method Animal husbandry was performed under licence from the Home Office (as per ASPA 1986). C3H/He mice (n = 44) were fed standard chow or HF/HS chow (trans-fats, with fructose corn syrup). At 24 weeks, feed was supplemented with an FXR agonist (5 mg/kg or 1 mg/kg of feed) or control. At 42 weeks, body weight and visceral adipose tissue (VAT) weight was recorded and the ileum was dissected. The expression of TNFα, IFNγ and IL-6 was measured by RT-PCR (ΔΔCt method). FXR and its downstream targets, SHP and IBABP, were measured to assay for FXR activity. T- tests, regression analysis and Pearson correlation were calculated using Prism version 6.0e. P values were 2-tailed, a P value of Results Mice fed a HF/HS diet were significantly heavier, with more VAT than mice on the control diet (mean weight of 49.9 g versus mean weight of 41.6 g, p Conclusion Animals fed a western lifestyle diet express more ileal inflammatory cytokine. There is a trend to suggest that supplementation with an FXR agonist reduces diet induced cytokine expression. By mediating dietary risk, FXR may be a potential therapeutic target in IBD, particularly to reduce relapses in patients with known disease. Disclosure of interest None Declared. References Ananthakrishnan AN. Gastroenterol Hepatol. 2013;9(6) Swann JR, Want EJ, et al . PNAS 2011;108(1) Vavassori P, Mencarelli A, et al . J Immunol. 2009;183 Gadaleta RM, van Erpecum KJ, et al . Gut 2011;60

Introduction By inducing epithelial barrier dysfunction, IBD associated inflammatory cytokines increase the leakiness of the gut mucosa, driving chronic inflammation. 1 Epithelial permeability increases, in part, due to cell-cell junction re-arrangement, mediated by myosin light chain kinase (MLCK). 2 FXR agonism has been shown to maintain the epithelial barrier in a mouse model of colitis. 3 The aim of this study was to assay the effect of FXR agonism on epithelial cell morphology in a human, gut-derived epithelial model of barrier dysfunction. Method Fully differentiated Caco-2 cells were cultured as a polarised monolayer and treated with TNFα, IFNγ or IL-6 with or without an FXR agonist. At 48 h, transmission electron microscopy was performed to assess for morphological re-arrangement of the cell-cell junction. Two independent researchers, blinded as to intervention, counted the number of morphological re-arrangements in 20 samples, chosen at random. RNA was isolated from IL-6 treated monolayers and the expression of MLCK was measured by RT-PCR (ΔΔCt method). Unpaired t- tests were calculated using Prism version 6.0e. All P values were 2-tailed, and a P value of 0.05 or less was considered significant. Results FXR agonism reduced the number of epithelial cell-cell junction fissures for monolayers stressed with IFNγ (mean 62.5% to 30%) and IL-6 (mean 69.5% to 42.5%). This was significant in the IFNγ group (p = 0.03), but failed to reach significance in the IL-6 group (p = 0.08). There were no, or few, morphological re-arrangements in control, FXR agonist only or TNFα treated monolayers. Cells stressed with IL-6 demonstrated a significant increase in the relative expression of MLCK (fold increase 435.4). The IL-6 induced upregulation of MLCK was completely abolished by co-treatment with FXR agonist. Conclusion Evidence is presented to demonstrate that FXR acts to maintain human, gut-derived epithelial cell morphology after stress with IFNγ and IL-6, probably via a mechanism involving the regulation of MLCK expression. FXR agonists are potential therapeutic compounds in the management of IBD. References Capaldo CT et al . Bioch. Bioph. Acta 2009;1788:864–871 Cunningham KE et al . Ann. N. Y. Acad. Sci . 2012;2058:34–42 Gadaleta RM et al . Gut 2011;60:463–472 Disclosure of interest None Declared.

Introduction Faecal Calprotectin (FCP) is a widely used biomarker of gastrointestinal (GI) mucosal inflammation. Many capsule enteroscopy (CE) services are receiving increased referrals of patients with abdominal symptoms combined with an elevated FCP (>50 µg/g) but normal gastroscopy, colonoscopy or radiology. There is little data on using FCP levels as a screening tool for selecting patients in whom CE will lead to a definitive diagnosis. Elevated FCP levels may indiscriminately drive investigations in endoscopy and imaging-negative patients who subsequently have normal findings at CE. We aimed to determine the incidence of inflammatory pathology on CE in patients with a raised FCP, and if a suitable concentration of the biomarker could be identified as a screening tool to avoid unnecessary CE. Method A single centre retrospective review of The Newcastle upon Tyne Hospitals CE database was conducted (Feb 2012–Feb 2015). Patients with GI symptoms (abdominal pain, diarrhoea, bloating, vomiting, weight loss) and a raised FCP (>50 µg/g) were identified. Findings at CE considered to be inflammatory were: erythema, ulceration, erosions and fissuring. Results 35 patients were identified with elevated FCP and GI symptoms. 45.7% (n = 16) had inflammation identified by CE and in 54.3% (n = 19) no inflammatory pathology was identified. The mean (+/-SE) FCP was higher in patients with evidence of inflammation at CE in comparison to those with no inflammation: 452.1 (95.8) µg/g vs. 206 (20.8) µg/g; p = 0.01. Stratifying patients according to FCP revealed that only 8.3% of patients (n = 1/12) with a FCP of 50–200 µg/g had inflammatory findings at CE. This rose to 58.3% of patients (n = 7/12) with a FCP of 201–300 µg/g, and 72.7% of patients (n = 8/11) with a FCP >300 µg/g. A threshold of 200 µg/g FCP revealed a sensitivity of 94.1% to predict inflammation at CE, with a specificity of 55.6%. This FCP threshold had a negative predictive value of 90.9%, and positive predictive value of 66.7% for CE inflammation. Conclusion In this small retrospective analysis of a sub-group of patients referred for CE with a FCP of >50 μg/g the likelihood of identifying inflammatory pathology at CE increased with rising FCP concentrations above 200 μg/g. A threshold of 200 μg/g provided a high negative predictive value for CE inflammation and may be a useful screening tool to reduce the requirement for CE in select patient groups. This retrospective analysis should be confirmed in a larger prospective cohort. Disclosure of interest None Declared.

G A A b st ra ct s versus HC (77.6 [36.9-141.0] vs 25.5 [17.8-42.8] ng/ml; p

Three common mutations in the CARD15 (NOD2) gene are known to be associated with susceptibility to Crohn disease (CD), and genetic data suggest a gene dosage model with an increased risk of 2-4-fold in heterozygotes and 20-40-fold in homozygotes. However, the discovery of numerous rare variants of CARD15 indicates that some heterozygotes for the common mutations have a rare mutation on the other CARD15 allele, which would support a recessive model for CD. We addressed this issue by screening CARD15 for mutations in 100 CD patients who were heterozygous for one of the three common mutations. We also developed a strategy for evaluating potential disease susceptibility alleles (DSAs) that involves assessing the degree of evolutionary conservation of involved residues, predicted effects on protein structure and function, and genotyping in a large sample of cases and controls. The evolutionary analysis was aided by sequencing the entire coding region of CARD15 in three primates (chimp, gibbon, and tamarin) and aligning the human sequence with these and orthologs from other species. We found that 11 of the 100 CD patients screened had a second potential pathogenic mutation within the exonic and periexonic sequences examined. Assuming that there are no additional pathogenic mutations in noncoding regions, our study suggests that most carriers of the common DSAs are true heterozygotes, and supports previous evidence for a gene dosage model. Four novel nonsynonymous mutations were detected, one of which would produce premature termination of translation c.2686C>T (p.Arg896X). Two potential DSAs--c.2107C>T (p.Arg703Cys) and g.2238T>A (c.74-7T>A)--were significantly associated with CD in the case control sample. Analysis of the evolution of CARD15 revealed strong conservation of the encoded protein, with identity to the human sequence ranging from 99.1% in the chimp to 44.5% in fugu. Higher primates possess an open reading frame (ORF) upstream of the putative initiation site in other species that encodes a further 27 N-terminal amino acids, while four regions of high conservation are observed outside of the known domains of CARD15, indicative of additional residues of functional importance. The strategy developed here may have general application to the assessment of mutation pathogenicity and genetic models in other complex disorders.

Background: Osteoporosis is an important cause of morbidity in patients with Crohn’s disease. The pathogenesis of reduced bone mineral density (BMD) is multifactorial. A range of genetic factors have been implicated in other populations of patients with osteoporosis. Aim: To investigate the influence of interleukin 6 ( IL-6 ), collagen type 1α1 ( COL1A1 ), and vitamin D receptor gene ( VDR ) single nucleotide polymorphisms (SNP) on BMD in patients with Crohn’s disease. Patients: A cohort of 245 well characterised patients with Crohn’s disease were recruited from the inflammatory bowel disease register at the Freeman Hospital and Royal Victoria Infirmary, Newcastle upon Tyne, and the Queen Elizabeth Hospital, Gateshead, UK. Methods: Patients were genotyped for IL-6 C-174G SNP, COL1A1 Sp1 binding site G T SNP, VDR Taq1 , and Fok1 SNPs, and CARD15 R702W, G908R, and L1007fs SNPs. BMD was measured at the lumbar spine (LSP) and hip using dual energy x ray absorptiometry. Results: A total of 158 female and 87 male patients, aged 24–70 years (mean 44), were recruited. There were no significant differences in the distribution of the tested SNPs when analysed for age, body mass index, pre/post-menopausal status, smoking, or steroid use. Two hundred and thirteen patients were genotyped for the IL-6 SNP. LSP and total hip BMD was significantly lower in patients with the GG genotype (48%) than the CC genotype (15%) (p = 0.041, p = 0.014). One hundred and eighty patients were genotyped for the COL1A1 SNP. There was no significant difference in BMD at LSP. Hip BMD was significantly lower in heterozygous patients compared with homozygous wild-types (p = 0.034). There were no significant differences in BMD between genotypes for the two VDR SNPs or the CARD15 genotypes examined. Conclusion: IL-6 and COL1A1 gene polymorphisms influence BMD in patients with Crohn’s disease but the particular VDR gene polymorphisms studied do not have a major effect.

Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases of the gastrointestinal system known as the inflammatory bowel diseases (IBD). Recently, Stoll and colleagues reported a novel finding of genetic variation in the DLG5 gene that is associated with IBD (CD and UC combined). We present here a study of the genetic variation described in that report in two well-powered, independent case-control cohorts and one family-based collection, and confirm the proposed association between IBD and the R30Q variant of DLG5 in two of the three studies. We are, however, unable to replicate the other proposed association to the common haplotype described in Stoll et al and suggest that this other finding could conceivably have been partially a statistical fluctuation and partially a result of LD with the replicated R30Q association. This study provides support for the hypothesis that DLG5 constitutes a true IBD risk factor of modest effect.

A patient with genetic hemachromatosis presented with a clinical picture suggesting malignancy and CT evidence of lesions in the right colon and liver. Colonoscopy failed to confirm the suspected diagnosis. Blood and stool cultures were positive for yersinia enterocolittica infection. This case illustrates the need to confirm clinically and radiologically suspected malignancy. It also serves as a model of how localized gastrointestinal pathology can result from the interaction of host genetic factors and specific microbial species.

M.A. van Leeuwen1, S. Veenbergen1, R. Kersseboom2, L.F. de Ruiter1, H. Raatgeep1, D.J. Lindenbergh-Kortleve1, Y. SimonsOosterhuis1, L. de Ridder1, G.J.A. Driessen3, J.C. Escher1, J.N. Samsom1 *. 1Erasmus Medical Centre Sophia Children’s Hospital, Dept. of Paediatric Gastroenterology, Rotterdam, 2Erasmus Medical Centre, Dept. of Clinical Genetics, Rotterdam, 3Erasmus Medical Centre, Dept. of Paediatric Infectious Disease and Immunology, Rotterdam, Netherlands

The diagnosis of irritable bowel syndrome (IBS) is made on clinical grounds with appropriate limited investigations to exclude organic disease. IBS is common and may have a significant impact on a patient’s quality of life. Psychological symptoms are common. IBS may benefit from pharmacological and non-pharmacological management. Specific measures should be directed towards the dominant symptoms of constipation or diarrhoea. Several new drugs are currently under evaluation and may prove valuable for subgroups of patients with IBS. Successful management requires a combination of reassurance and explanation about the natural history of the condition.

Introduction The revised NICE guidance on the use of infliximab and adalimumab for the treatment of Crohn9s disease, released in May 2010, has suggested biologics be prescribed as a planned therapy until treatment failure or until completion of 12 months treatment, whichever is shorter. For the first time, NICE have introduced cost as a criteria for which anti-TNF antibody treatment should be used, recommending that therapy be commenced with the less expensive of the two drugs. However the comparative cost of the drugs is not immediately clear. For example the dosage of infliximab is weight dependent, whereas the dosage of adalimumab is independent of weight; and the dosage interval of both drugs may be shortened to optimise efficacy. These factors may impact on cost. Methods As part of a service development exercise, a retrospective audit of patient records was performed. The drug cost of infliximab and adalimumab prescription per patient for the treatment of Crohn9s disease in the Trust between 1 April 2009 and 31 March 2010 was calculated. Results Of 60 patients receiving biologics, 46 patients were treated with infliximab and 19 patients with adalimumab during the 1-year audit period (5 patients received both drugs during the study period). The mean age (range) of the cohort was 32.4 years (17–65). The median cost of infliximab was £6294 per patient (mean (95% CI) cost, £6877 (5783 to 7971) per patient). The median cost of adalimumab was £5720 per patient (mean (95% CI) cost, £8226 (4893 to 11 560) per patient). There was no significant cost difference between the drugs (p=0.43). Conclusion In this cohort of patients, no significant cost difference was found when comparing infliximab and adalimumab for the treatment of Crohn9s disease over a 1-year period. In light of the recent NICE guidance, this data would support individual patient and physician choice when deciding on which anti-TNF therapy to prescribe.

Introduction Crohn’s disease (CD) is now understood to be caused by the interaction between genetic and environmental factors with dysregulation of gut microbiota playing a pivotal role. NOD2 , the strongest genetic risk factor for CD, encodes a pattern recognition receptor and plays an important role in epithelial defence. Studies of NOD2 -knockout mice have demonstrated shifts in gut microbiota. Human studies to date have been limited by relatively small numbers of individuals homozygous for NOD2 mutations without accurate matching of controls. Methods Individuals with CD of known NOD2 status were identified from the UK IBD genetics consortium. Patients in clinical remission were selected if they carried 2 of the common NOD2 variants (homozygotes or compound heterozygotes). Each NOD2 mutant patient was matched to a NOD2 wild-type patient. For all CD patients a household control was approached. Healthy volunteers stratified by NOD2 genotype were recruited from the Cambridge Bioresource. Faecal samples were frozen within 24h of collection. DNA was extracted using the FASTDNA Spin Kit for Soil. The V1–3 region of the 16S rRNA gene was amplified and amplicons were sequenced with Illumina MiSeq. Sequence data was processed in Mothur. Calprotectin was measured in all samples by ELISA. Results 97/107 individuals were included in the primary analysis (40 CD patients [58% NOD2 mutant], 32 bioresource volunteers [50% NOD2 mutant], 25 household controls). The minimum reads per sample were 3953, mean 21216. There was a significant reduction in diversity (inverse Simpson index), Ruminococcaceae including Faecalibacteria and increase in Enterobacteriaceae in samples from CD patients vs. controls (all p NOD2 status, either within the CD patients or bioresource controls. Conclusion This study confirms previously identified shifts in gut microbiota in CD patients. However, no significant differences in gut microbiota were seen when analysed by NOD2 status. This may be a reflection of sample size or of studying gut bacteria in stool as opposed to the mucosally-associated compartment. We are presently recruiting additional cases and controls to increase study power for additional analysis. Disclosure of Interest None Declared.

Introduction Infliximab and adalimumab have established roles in IBD therapy. NICE and SMC guidelines mandate reassessment of disease activity after 12 months. Therapy should ordinarily be discontinued where clinical remission and mucosal healing has been achieved. However, there are presently few data about outcomes of anti-TNF withdrawal. Methods We conducted a retrospective clinical audit of outcomes following withdrawal of anti-TNF therapy. Inclusion criteria were confirmed diagnosis of IBD; ≥12 m continuous anti-TNF therapy; primary withdrawal reason sustained clinical remission (no corticosteroids for 6 m); ≥12 m follow-up post-withdrawal. Relapse was defined as moderate (oral steroids, immunomodulators, recommencement of anti-TNF agent) or severe (hospitalisation, iv steroids, surgical resection). All UK centres were invited to participate. Demographic and phenotypic data plus clinical, laboratory and endoscopic parameters were recorded. Results 80 cases (62 infliximab; 18 adalimumab) with a median follow-up time of 26 m post drug withdrawal were included in this analysis (59% female; median age at drug withdrawal 32y). All were in clinical remission at withdrawal; 47/80 had normal laboratory parameters (Hb, WCC, plts, Albumin, CRP, FC) prior to withdrawal. 49/80 had endoscopic re-evaluation with mild disease noted on 9/50 and moderate on 1. 23/70 (33%; 2/23 severe) of patients with Crohn’s disease relapsed by 12 months and 49% relapse (3/35 severe) by 24 months (Fig 1, median time to relapse 10.4 m). Younger age at diagnosis (p = 0.017) and elevated WCC (p = 0.025), but not CRP or faecal calprotectin, were predictive of relapse. 4/10 (none severe) with UC/IBDU had relapsed by 12 and 24 months. Anti-TNF therapy was re-introduced in 30 patients following relapse and was successful in 93%. Conclusion Planned withdrawal of anti-TNF therapy for sustained clinical remission is associated with a moderate relapse of Crohn’s disease in up to half of patients by 2 years. Data collection of an expanded cohort is ongoing around the UK to improve power to dissect predictive factors at time of drug withdrawal. Disclosure of Interest None Declared.

Introduction The concept of using faecal biomarkers to predict prognosis and direct treatment in patients with Crohn’s disease is attractive but long term follow-up data is lacking. A cohort of 51 patients with previous ileal resections for Crohn’s disease provided a one-off stool sample for faecal calprotectin (FC). These patients were followed up for 5 years to assess whether FC could predict disease progression in the long term. Methods Patients were identified from a database of patients who had participated in a previous study evaluating the use of FC in post-operative Crohn’s. Patients were included in the study if they had been followed up for at least 5 years after the initial FC was recorded. Case notes were reviewed retrospectively and information on the need for escalation of medical therapy or for further surgery for disease recurrence was recorded. A FC of more than 200 was taken as the cut-off value for evidence of active inflammation. Statistical analysis was performed using Prism 6 (GraphPad Software, San Diego, USA). Results 17 patients had a FC ≥ 200 (median 751, IQR 593–916). Of these 13 required either escalation of medical treatment and/or further surgery over the 5 year follow-up period. 34 patients had a FC Conclusion A FC of less than 200 predicts a better prognosis in patients with post-op Crohn’s disease over a prolonged (5 year) period and could therefore potentially be used to stratify treatment and target early intervention. Disclosure of Interest None Declared.

Increased Expression of T Cell Associated Genes in Baseline Biopsies From TNF Antagonist Naive Patients That Achieve Remission With Etrolizumab Treatment in a Phase II Trial in Moderate to Severely Active Ulcerative Colitis Gaik Wei Tew, Jason Hackney, Deena L. Gibbons, Christopher A. Lamb, Diana Luca, Jackson G. Egen, Severine Vermeire, John C. Mansfield, Brian G. Feagan, Julian Panes, Daniel C. Baumgart, Stefan Schreiber, Iris Dotan, William Sandborn, John A. Kirby, Gert De Hertogh, Gert A. Van Assche, Paul J. Rutgeerts, Sharon O'Byrne, Adrian C. Hayday, Mary E. Keir

P653 Genetic predictors of non reversible tissue damage in inflammatory bowel disease J.M. Benitez1 *, J.M. Mahachie John2, E. Theâtre3, C. Reenaers3, M. De Vos4, O. Dewit5, K. Van Steen2, E. Louis3. 1Reina Sofia University Hospital, IMIBIC, CHU Liege, Gastroenterology, Cordoba, Spain, 2CHU de Liege, Bioinformatics and Modeling, Liege, Belgium, 3CHU de Liege, GIGA, Gastroenterology, Liege, Belgium, 4Ghent University Hospital, Gastroenterology, Ghent, Belgium, 5Saint-Luc Hospital, Gastroenterology, Brussels, Belgium

s of the 9th Congress of ECCO the European Crohn’s and Colitis Organisation S7 (biventricular heart dysfunction and sepsis) that occurred between wks 54 and 104. Conclusions: These data continue to support a positive benefit/ risk profile for GLM in the treatment of moderate to severe UC; GLM treatment for up to 2 y maintained clinical benefit including a reduction in corticosteroid use. No new safety signals were observed with continued GLM treatment through wk 104; safety profile was similar to wk 54. OP010 AlphaE integrin expression as a predictive biomarker for induction of clinical remission by etrolizumab: Analysis of a phase II trial in moderate-to-severely active ulcerative colitis M. Keir1 *, G.W. Tew1, D. Luca1, J. Eastham-Anderson1, L. Diehl1, J.G. Egen1, S. Vermeire2, J.C. Mansfield3, C.A. Lamb3, J. Panes4, D.C. Baumgart5, S. Schreiber6, I. Dotan7, W.J. Sandborn8, G. De Hertogh2, J.A. Kirby3, G. Van Assche2, P. Rutgeerts2, S. O’Byrne1. 1Genentech, Research and Early Development, South San Francisco, United States, 2KU Leuven, Division of Gastroenterology, Leuven, Belgium, 3Royal Victoria Infirmary, Gastroenterology, Newcastle upon Tyne, United Kingdom, 4Hospital Clinic Barcelona, Gastroenterology, Barcelona, Spain, 5HumboldtUniversity of Berlin, Charite Medical School, Berlin, Germany, 6Christian Albrechts University, Institute of Clinical Molecular Biology, Kiel, Germany, 7Tel Aviv University, Sackler Faculty of Medicine, Tel Aviv, Israel, 8University of California, San Diego, Gastroenterology, San Diego, United States Background: Etrolizumab is a humanized monoclonal antibody to the beta7 integrin subunit that blocks alpha4beta7: MAdCAM-1 and alphaEbeta7:E-cadherin interactions and has been shown to be effective at inducing remission in patients with moderate to severely active ulcerative colitis (UC). Methods: Patients enrolled in the Phase 2 study of etrolizumab in UC were assessed for baseline biopsy gene expression of MAdCAM1, alphaE and alpha4 integrin by qPCR (n = 106) as well as baseline alphaE+ cells per total cells in biopsies from the inflamed colon by immunohistochemistry (n = 76). Enrichment of baseline measures was evaluated using the primary outcome measure of the study, remission at week 10, defined as a total MCS of 2 with no individual subscore >1. Results: AlphaE gene expression and alphaE+ cells were lognormally distributed in baseline biopsies from UC patients. No difference in baseline characteristics was observed between alphaE high and alphaE low groups. Enrichment in response to treatment with 100mg/dose etrolizumab as measured by remission was observed in patients with higher than median levels of alphaE gene expression at screening (38% alphaE high vs. 13% alphaE low). No enrichment was observed in alpha4 high patients (27% alpha4 high vs. 24% alpha4 low) or MAdCAM1 high patients (27% MAdCAM1 high vs. 24% MAdCAM1 low). Enrichment in response to treatment as measured by remission was observed in TNF antagonist naive patients with high levels of alphaE gene expression at screening (67% alphaE high vs. 17% alphaE low). Similarly, enrichment of remission in response to treatment was observed in patients with higher than median levels of alphaE+ cells per total cells (50% alphaE high vs. 7% alphaE low). TNF antagonist naive patients with high levels of alphaE+ cells per total cells at screening had enriched response to treatment with etrolizumab as measured by remission (67% alphaE high vs. 25% alphaE low). Conclusions: These results suggest that higher than median levels of alphaE gene expression and/or alphaE+ cells per total cells in the inflamed colon are associated with increased clinical benefit of etrolizumab treatment in patients. Thus alphaE gene expression or alphaE+ cells in colonic biopsies may be predictive biomarkers to identify UC patients most likely to benefit from etrolizumab treatment. OP011 Tralokinumab (CAT-354), an interleukin 13 antibody, in moderate to severe ulcerative colitis: A phase 2 randomized placebo-controlled study S. Danese1, J. Rudzinski2, W. Brandt3, J.L. Dupas4, L. Peyrin-Biroulet5, Y. Bouhnik6, D. Kleczkowski7, P. Uebel8, M. Lukas9, M. Knutsson10, F. Erlandsson10, M. Berner Hansen10 *, S. Keshav11. 1Istituto Clinico Humanitas, IBD Center, Milan, Italy, 210 Wojskowy Szpital Kliniczny z Poliklinik?, Kliniczny Oddzia? Gastroenterologii, Warsaw, Poland, 3Facharzt fur Innere Medizin, Internal Medicine, Potsdam, Germany, 4CHU d’Amiens Hopital Nord, Hepato-Gastroenterology, Amiens, France, 5CHU Nancy Brabois, Gastrology, Vandoeuvre les Nancy, France, 6Hopital Beaujon APHP, Gastroenterologie, Clichy, France, 7Endoskopia Sp.z o.o., Gastroenterology, Sopot, Poland, 8Haus der Gesundheit, Internal Medicine, Ludwigshafen, Germany, 9Iscare, Gastroenterology, Prague, Czech Republic, 10AstraZeneca, Innovative Medicines, Molndal, Sweden, 11John Radcliffe Hospital, Translational Gastroenterology Unit, Oxford, United Kingdom Background: Interleukin 13 (IL-13) is a central cytokine effector in the Th2 immune response and potentially a key player in ulcerative colitis (UC) pathogenesis. Tralokinumab (CAT-354) is a humanized IgG4 antibody that binds and inhibits IL-13. The purpose of this study was to evaluate the efficacy and safety of tralokinumab in subjects with moderate to severe active UC. Methods: Subjects (18 75 yrs) with UC and total Mayo score 6 12 received tralokinumab or placebo as add-on therapy in this European multicenter, randomized, double-blind, placebocontrolled study sponsored by AstraZeneca (ClinicalTrials.gov #NCT01482884). Subjects received subcutaneous tralokinumab (300mg) or placebo every 2 wks during a 12-wk treatment phase followed by a 12-wk safety follow-up. The primary endpoint was clinical response at wk 8 defined as a reduction of 3 points and 30% or more from baseline total Mayo score. Secondary endpoints included clinical remission (Mayo score 2 with no subscore >1 point), mucosal healing (endoscopic Mayo score 0), improvement in Mayo score at wk 8, partial Mayo score, and safety. Allowed background medications included stable doses of 5-ASA, prednisolone ( 20mg daily), and thiopurines. Results: 111 subjects were randomized (tralokinumab n = 56; placebo n = 55). Baseline subject and disease characteristics were similar in both arms. The median baseline Mayo score was 8 in both arms; 23% and 31%, respectively, had received prior TNF-a therapies; 43 (77%) tralokinumab subjects and 37 (67%) placebo subjects, respectively, completed the study. Improvements in mean partial Mayo scores were greater in the tralokinumab subjects ( 1.8 vs. 0.8, p = 0.04). Results at week 8 Tralokinumab Placebo P value Clinical response (%) 38 33 0.41 Clinical remission (%) 18 6 0.03 Mucosal healing (%) 32 20 0.10 Mean improvement in Mayo Score 3.2 2.6 0.39 Serum eosinophil counts and total IL-13 levels increased during therapy with tralokinumab. Symptoms of UC were the most frequently reported adverse events (AEs). The number of subjects experiencing AEs and AEs leading to discontinuation of drug were similar in both groups. There were no clinically relevant changes in laboratory variables, vital signs, and electrocardiograms. No new safety signals were identified for tralokinumab. Conclusions: Multiple efficacy measures were numerically higher in the tralokinumab arm. However, the difference in clinical response at wk 8 (primary endpoint) between by gest on Feruary 5, 2016 http://eccoxfordjournals.org/ D ow nladed from