Simen Vatn

Biosimilar infliximab (CT-P13) in the treatment of inflammatory bowel disease: A Norwegian observational study

Objective: To assess the efficacy, tolerability, and safety of CT-P13 (Remsima®) in patients with Crohn’s disease (CD) or ulcerative colitis (UC). Methods: This was a prospective observational study performed in a single center in Norway. Patients with CD (n = 46) or UC (n = 32) received CT-P13 (5 mg/kg) by intravenous infusion at weeks 0, 2, and 6. Efficacy end points included remission at week 14, measured by a Harvey-Bradshaw Index score of ≤4 or partial Mayo score of ≤2. Levels of the inflammatory markers C-reactive protein and calprotectin were measured. Adverse events up to week 14 were also recorded. Results: Seventy-nine percent of CD and 56% of UC patients achieved remission at week 14. Significant reductions in C-reactive protein and calprotectin occurred between baseline and week 14. There were no unexpected adverse events reported during the study. Conclusion: CT-P13 is efficacious and well tolerated in patients with CD or UC.

Simultaneous purification of DNA and RNA from microbiota in a single colonic mucosal biopsy

BackgroundNucleic acid purification methods are of importance when performing microbiota studies and especially when analysing the intestinal microbiota as we here find a wide range of different microbes. Various considerations must be taken to lyse the microbial cell wall of each microbe. In the present article, we compare several tissue lysis steps and commercial purification kits, to achieve a joint RNA and DNA purification protocol for the purpose of investigating the microbiota and the microbiota-host interactions in a single colonic mucosal tissue sample.ResultsA further optimised tissue homogenisation and lysis protocol comprising mechanical bead beating, lysis buffer replacement and enzymatic treatment, in combination with the AllPrep DNA/RNA Mini Kit (Qiagen, Hilden, Germany) resulted in efficient and simultaneous purification of microbial and human RNA and DNA from a single mucosal colonic tissue sample.ConclusionsThe present work provides a unique possibility to study RNA and DNA from the same mucosal biopsy sample, making a direct comparison between metabolically active microbes and total microbial DNA. The protocol also offers an opportunity to investigate other members of a microbiota such as viruses, fungi and micro-eukaryotes, and moreover the possibility to extract data on microbiota and host interactions from one single mucosal biopsy.

P866 Faecal microbiota in newly diagnosed Crohn’s disease and its relation to treatment escalation

Faecal microbiota in newly diagnosed Crohns disease and its relation to treatment escalation

OP022 Proximity extension assay based proteins show immune cell specificity and can diagnose and predict outcomes in inflammatory bowel diseases: IBD Character study

Proximity extension assay based proteins show immune cell specificity and can diagnose and predict outcomes in inflammatory bowel diseases : IBD Character study

P788 Microbiota related disease activity and distribution in subgroups of inflammatory bowel disease

Microbiota related disease activity and distribution in subgroups of inflammatory bowel disease

Epigenetic alterations at diagnosis predict susceptibility, prognosis and treatment escalation in inflammatory bowel disease - IBD Character

Epigenetic alterations at diagnosis predict susceptibility, prognosis and treatment escalation in inflammatory bowel disease - IBD Character

Proximity Extension Assay based Proteins Show Immune Cell Specificity and can Diagnose and Predict Outcomes in Inflammatory Bowel Diseases: IBD Character Study

Introduction Proximity extension assays (PEA) allows multiprotein profiling and utilises the specificity of antibody proximity and the sensitivity of polymerase chain reaction to detect proteins of interests. As part of IBD Character, we performed high-throughput prospective case-control serum profiling to identify proteins that can predict Inflammatory Bowel Disease (IBD) and its disease course. Method Serum profiling was performed in newly diagnosed IBD and Non-IBD cases using PEA panels (Olink Proteomics) from 6 centres in Europe. Phenotypic data were obtained for all patients and follow up outcome data were captured for the Edinburgh and Oslo IBD cohorts. Treatment escalation was defined as the need for surgery and/or biologic therapies after initial induction of remission. Statistical analysis was performed using R. Results Protein profiles were available in 635 patients (152 CD, 159 UC, 26 IBD-U, 298 non-IBD). 61 protein markers were significantly associated with IBD including MMP12 (Holm-adjusted p=4.1×10–26). Mapping top markers to cell-specific FANTOM 5 [1], several differentially expressed proteins originate from innate and adaptive immune cells such as dendritic cells. 5 proteins differentiate UC from CD including MMP-12 (p=4.6×10–4) Follow up data were available for 206 patients of which 49 patients required treatment escalation. The data were randomly split into a testing (n=130) and a validation cohort (n=76). Using multivariable analyses with age, sex and follow up time as covariates, 9 proteins survived Holm adjustment and 8 of these proteins remained signficant in the validation cohort. 1000 iterations of unsupervised linear discriminant consensus clustering were performed using 7 randomly selected top proteins and identified 2 patients groups that had significantly different disease courses(Image):logrank p=2.2×10–10, HR 5.6 (2.0–15.6); outperforming conventional biomarkers in predicting treatment escalation (hsCRP >4 mg/L, HR 3.2 (1.7–5.8), p=0.0003 and Alb Conclusion We have identified immune cell-specific PEA-based serum proteins that can diagnose IBD and predict disease course. These data demonstrate the translational potential of a PEA based technology in IBD Reference . FANTOM Consortium(2014), A promoter level mammalian expression atlas, Nature2014, 507:462–70 Disclosure of Interest R. Kalla: None Declared, A Adams Conflict with: EC FP7, S Vatn: None Declared, D Bergemalm: None Declared, P Ricanek: None Declared, J Lindstrom: None Declared, A Ocklind Conflict with: Olink is an SME within IBD Character, N Nordberg Conflict with: Olink is an SME within IBD Character, N Kennedy: None Declared, N Ventham: None Declared, M Vatn: None Declared, J Soderholm: None Declared, M Pierik: None Declared, L Torkvist: None Declared, F Gomollon: None Declared, J Jahnsen: None Declared, J Halfvarson: None Declared, J Satsangi: None Declared

EPIGENETIC ALTERATIONS AT DIAGNOSIS PREDICT SUSCEPTIBILITY, PROGNOSIS AND TREATMENT ESCALATION IN INFLAMMATORY BOWEL DISEASE AND IBD CHARACTER

Epigenetic alterations at diagnosis predict susceptibility, prognosis and treatment escalation in inflammatory bowel disease - IBD Character