Late‐breaking abstracts

Abstract

United European Gastroenterology JournalVolume 3, Issue 6 p. 561-571 AbstractsOpen Access Late-breaking abstracts First published: 01 December 2015 https://doi.org/10.1177/2050640615616068AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat OP054-LB1 A CONTROLLED CROSS-OVER TRIAL SHOWS BENEFIT OF PRUCALOPRIDE FOR SYMPTOM CONTROL AND GASTRIC EMPTYING IN GASTROPARESIS F. Carbone1, A. Rotondo1, C. Andrews1, L. Holvoet2, L. Van Oudenhove1, T. Vanuytsel2, R. Bisschops2, P. Caenepeel2, J. Arts2, A. Papathanasopoulos1 and J. Tack1 1 TARGID, Leuven Unversity and Leuven University Hospitals 2 Gastroenterology, Leuven University Hospitals, Leuven, Belgium Contact E-mail Address: jan.tack@med.kuleuven.be Introduction: Gastroparesis is a chronic gastric disorder characterised by delayed gastric emptying without mechanical obstruction, and clinical symptoms such as post-prandial fullness, early satiety, bloating, nausea and vomiting. Prokinetics are considered the preferred treatment option for gastroparesis, but evidence of their efficacy is lacking. Prucalopride, a selective 5-hydroxytryptamine4 receptor (5-HT4 R) agonist used in the treatment of constipation, is able to enhance gastric emptying rate. Aims & Methods: In a single-center double-blind, randomized, placebo-controlled cross-over study we evaluated the efficacy of prucalopride to improve gastric emptying rate and symptoms in idiopathic or diabetic gastroparesis patients. 34 gastroparesis patients (28 idiopathic, mean age 43.5 ± 2.3, 8 men) underwent a 13 C-octanoic acid solid gastric emptying breath test, and symptom severity assessment by the Gastroparesis Cardinal Symptoms Index (GCSI) at run-in and at the end of 4 weeks blinded cross-over treatment periods with placebo or prucalopride 2 mg q.d., separated by 2 weeks wash-out. Results: Three patients were lost to follow-up. One serious adverse event occurred (small bowel volvulus in the prucalopride group), and 4 patients dropped out because of adverse events of nausea and headache (1 placebo, 3 prucalopride). Prucalopride significantly enhanced gastric half emptying time compared to placebo and to baseline (87.9 ± 8.2 vs 117.9 ± 14.4 and 139.2 ± 11.8 min, p < 0.05 and <0.005 respectively). In addition, prucalopride, compared to placebo and to baseline, also significantly improved the GCSI subscales of fullness/satiety (2.03 ± 0.27 vs 2.77 ± 0.28 and 3.07 ± 0.26, both p < 0.0005), nausea/vomiting (1.04 ± 0.23 vs 1.49 ± 0.27 and 1.77 ± 0.24, p = 0.01 and <0.0001 respectively) and bloating/distention (1.30 ± 0.25 vs 2.35 ± 0.30 and 2.89 ± 0.31, both p < 0.00001). With placebo, only the bloating/distention subscale differed significantly from baseline. Compared to both baseline or placebo, prucalopride significantly improved the overall PAGI-QOL score, and the domains of clothing and diet (all p < 0.01). Conclusion: In gastroparesis patients, 4 weeks of prucalopride treatment significantly enhances gastric half emptying time and improves symptoms and quality of life compared to placebo and to baseline. Disclosure of Interest: None declared. OP054-LB2 GASTROINTESTINAL EVENTS AND ADVERSE REACTIONS ON SELECTIVE AND NON SELECTIVE CYCLOOXYGENASE INHIBITORS IN THE LARGE RANDOMISED CONTROLLED SCOT TRIAL C. Hawkey1, J. Scheiman2, J. Dillon3, A. Lanas4, J. Moeller5, J. Hallas6, I. Ford7, N. Greenlaw7, I. Mackenzie3 and T. MacDonald3 1 University of Nottingham, Nottingham, United Kingdom 2 University of Michigan, Michigan, Canada 3 Ninewells Hospital, Dundee, United Kingdom 4 University of Zaragoza, Zaragoza, Spain 5 Odense University Hospital 6 University of Southern Denmark, Odense, Denmark 7 University of Glasgow, Glasgow, United Kingdom Contact E-mail Address: cj.hawkey@nottingham.ac.uk Introduction: Non-selective non-steroidal anti-inflammatory drugs (nsNSAIDs) are associated with adverse gastrointestinal (GI) events which may reduce with selective cyclooxygenase-2 (COX-2) inhibitors, though both may increase cardiovascular (CV) events. We compared the COX-2 inhibitor celecoxib with nsNSAIDs in a large pragmatic trial using record linkage. Aims & Methods: Patients aged ≥60 years, without CV disease, taking chronic nsNSAIDs in primary care, were randomised to celecoxib or continued nsNSAID. The primary endpoint was non-fatal myocardial infarction, biomarker positive acute coronary syndrome, stroke or CV death and the secondary (GI) endpoint adjudicated ulcer complications. Results: A total of 7297 participants (38% on ulcer healing drug) were randomised and followed for median 3 years. The CV endpoint occurred at a low rate of 0.95/100 patient years on celecoxib vs 0.86/100 on nsNSAIDs (on treatment (OT) analysis; 1.14 vs 1.10/100 by intention to treat (ITT)). There were only 15 adjudicated secondary (GI) endpoints (0.10/100 patient years on celecoxib vs 0.05 on nsNSAIDs OT, 0.09 vs 0.04 ITT). There were 218 deaths (CV: 33.3% celecoxib vs 35.3% nsNSAIDs, neoplasia: 39.2% vs 29.3%, non-malignant respiratory: 14.7% vs 12.9%) with only 2 attributed to GI bleeding (celecoxib). Serious adverse events were similar for each group (celecoxib 31.7%, ns-NSAID 32.4%) but adverse reactions (ARs) attributed to trial treatment were reported in 22.0% celecoxib vs 16.1% nsNSAIDS (p < 0.001), including 10.6% vs 9.1% GI (p = 0.04). There were more GI serious ARs on nsNSAIDs than celecoxib (1.8% vs 1.0%, p = 0.007) with 10 vs 2 reports of rectal haemorrhage and 13 vs 3 of gastritis. Haematological ARs were reported in more nsNSAID than celecoxib patients (1.3% vs 0.7%) due to to more patients with anaemia or iron deficiency anaemia (1.3% vs 0.6%). During follow-up, 50.9% patients withdrew from celecoxib compared to 30.2% from all nsNSAIDs (p < 0.001). Conclusion: Prescribing celecoxib to patients previously on nsNSAIDs did not significantly alter risk of adjudicated CV or GI endpoints. Some new ARs emerged, contributing to withdrawal, but there appeared to be fewer rectal haemorrhage and gastritis SARs and fewer ARs due to anaemia. Causes of death were similar to those seen in unselected patients and GI bleeding was an uncommon cause. Disclosure of Interest: C. Hawkey Financial support from: Univ Dundee, NIHR, HTA, Consultancy for: Bayer, InDex Pharma, Novartis/GSK, J. Scheiman: None declared, J. Dillon: None declared, A. Lanas: None declared, J. Moeller: None declared, J. Hallas: None declared, I. Ford: None declared, N. Greenlaw: None declared, I. Mackenzie: None declared, T. MacDonald Financial support from: Novartis, Pfizer, Amgen, Ipsen, Teijin, Menarini, Consultancy for: Pfizer, Novartis, Kaiser Permanente, Takeda, Servier, Shire, Astellas, Menarini, AstraZeneca, Daiicho Sankyo, Lundbeck. OP54-LB3 ENDOSCOPIC FULL THICKNESS RESECTION IN THE LOWER GASTROINTESTINAL TRACT USING AN OVER-THE-SCOPE DEVICE – PRELIMINARY RESULTS OF A PROSPECTIVE MULTICENTRE TRIAL A. R. Schmidt1, B. Schumacher2, D. Albers3, H. Neuhaus4, M. Nübel4, H. Messmann5, A. Probst5, A. Meining6, M. Birk6, H.-J. Richter-Schrag7, A. Fisher7, T. Frieling8, M. Götz9 and K. Caca10 1 Department of Gastroenterology, Klinikum Ludwigsburg, Ludwigsburg 2 Elisabeth Krankenhaus, Essen 3 Department of Gastroenterology, Elisabeth Krankenhaus, Essen 4 Evangelisches Krankenhaus Düsseldorf, Düsseldorf, 5 Klinikum Augsburg, Augsburg 6 Universitätsklinikum Ulm, Ulm 7 Klinik für Innere Medizin II, Universitätsklinikum Freiburg, Freiburg 8 Helios Klinikum Krefeld, Krefeld 9 Universitätsklinikum Tübingen, Tübingen 10 Klinikum Ludwigsburg, Ludwigsburg, Germany Contact E-mail Address: arthur.schmidt@kliniken-lb.de Introduction: The Full Thickness Resection Device (FTRD) (Ovesco, Tübingen, Germany) is a novel over-the-scope device which is approved for full-thickness resection in the lower gastrointestinal (GI) tract in Europe since September 2014. A recent retrospective study has suggested that device and technique is safe and effective. Aims & Methods: We are conducting a prospective, uncontrolled, multicenter trial at 7 academic referral centers in Germany (NCT02362126). Primary endpoints of the study are technical success and R0-resection, secondary endpoints are occurrence of adverse events. Here, we report the results of an interim analysis while the study is still recruiting. Between February 2015–August 2015, 74 patients with indication for full thickness resection in the colorectum were included in the study. Results: Indications for endoscopic full thickness resection were: recurrent, incompletely resected or untreated non-lifting adenomas (43); adenoma involving the appendix (11), T1-carcinoma (8), adenoma involving a diverticulum (2) and subepithelial tumors (10). The lesions were located as followed: coecum (19), ascending colon (15), transverse colon (13), descending colon (3), sigmoid (11), recosigmoid transition (4) and rectum (10). Reaching the target lesion with the endoscope and the mounted FTRD was possible in all patients (100%). Technical success (macroscopically complete and en bloc resection) was achieved in 64 (86.4%) patients. R0-resection rate was 80.1 %. One secondary perforation at the resection site requiring surgical therapy and two minor bleedings were observed. No other severe complications have been recorded so far. Conclusion: The interim results of this prospective study indicate that full thickness resection in the lower GI tract with the novel FTRD is feasible, effective and safe. Final results including follow up data will be expected by mid of 2016. Disclosure of Interest: A. Schmidt Lecture fee(s) from: Ovesco Endoscopy, B. Schumacher: None declared, D. Albers: None declared, H. Neuhaus: None declared, M. Nübel: None declared, H. Messmann: None declared, A. Probst: None declared, A. Meining: None declared, M. Birk: None declared, H.-J. Richter-Schrag: None declared, A. Fisher: None declared, T. Frieling: None declared, M. Götz: None declared, K. Caca Lecture fee(s) from: Ovesco Endoscopy. References References 1Schmidt A, Damm M, Caca K. Endoscopic full thickness resection using a novel over-the-scope device. Gastroenterology 2014; 47: 740– 743. Google Scholar 2Schmidt A, Bauerfeind P, Gubler C, et al. Endoscopic full thickness resection in the colorectum with a novel over-the-scope device – first experience. World J Gastroenterol 2015; 21 (31): 9273– 9285. Published online 21 August 2015. DOI: https://doi.org/10.3748/wjg.v21.i31.9273. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4541380/ CrossrefPubMedWeb of Science®Google Scholar OP054-LB4 A MULTICENTER, DOUBLE-BLIND, PLACEBO-CONTROLLED PH3 STUDY OF USTEKINUMAB, A HUMAN MONOCLONAL ANTIBODY TO IL-12/23P40, IN PATIENTS WITH MODERATELY-SEVERELY ACTIVE CROHN'S DISEASE WHO ARE NAÏVE OR NOT REFRACTORY TO ANTI-TNFΑ: UNITI-2 B. Feagan1, C. Gasink2, Y. Lang2, J. R. Friedman2, J. Johanns2, L.-L. Gao2, B. Sands3, S. Hanauer4, P. Rutgeerts5, S. Targan6, S. Ghosh7, W. de Villiers8, J.-F. Colombel3, Z. Tulassay9, U. Seidler10 and W. J. Sandborn11 1 Robarts Research Institute, London, Canada 2 Janssen R&D, LLC, Spring House 3 Mt Sinai Medical Center, New York 4 Northwestern University, Chicago, United States 5 University Hospital Gasthuisberg, Leuven, Belgium 6 Cedars-Sinai Medical Center, Los Angeles, United States 7 University of Calgary, Calgary, Canada 8 University of of Cape Town, Cape Town, South Africa 9 Semmelweis University, Budapest, Hungary 10 Hannover Medical School, Hannover, Germany 11 UCSD, La Jolla, United States Contact E-mail Address: MRittenh@its.jnj.com Introduction: In the Ph 2b Crohn's Evaluation of Response to Ustekinumab anti-IL12/23 for Induction study, a single intravenous ustekinumab induction dose was effective and safe in Crohn's disease patients (pts) previously failing anti-tumor necrosis factors,1 but efficacy in pts only failing conventional therapy is unknown. We evaluated 2 intravenous ustekinumab induction dose-regimens in a Crohn's disease population not refractory to anti-tumor necrosis factors. Aims & Methods: Pts with moderate-severely active Crohn's disease (CDAI220–450) who failed conventional therapy but were not refractory to anti-tumor necrosis factors were randomized to a single dose of intravenous placebo, ustekinumab 130 mg, or weight-based tiered ustekinumab dosing ∼6 mg/kg. Primary endpoint was clinical response at Wk 6 (reduction in Crohn's Disease Activity Index score of ≥100 pts). At Wk 8, pts transitioned to IM-UNITI maintenance study or had safety follow-up through Wk 20. Results: Of 628 pts randomized, median disease duration was 6.4 years; baseline (BL) mean Crohn's Disease Activity Index was 303; 39% and 35% were receiving steroids and immunomodulators, respectively at BL; 69% were naïve to anti-tumor necrosis factors. At Wk 6, 55.5% and 51.7% in ∼6 mg/kg and 130 mg ustekinumab groups were in clinical response vs 28.7% placebo (p < 0.001). At Wk 8, 40.2% and 30.6% of pts in ∼6 mg/kg and 130 mg ustekinumab groups were in clinical remission vs 19.6% placebo (p ≤ 0.009). Both ustekinumab doses showed significant improvements vs placebo in Crohn's Disease Activity Index, Inflammatory Bowel Disease Questionnaire, C reactive protein, and fecal lactoferrin and fecal calprotectin. Proportions of adverse events, serious adverse events, and infections (including serious infections) were similar in ustekinumab and placebo groups. No malignancies, deaths, opportunistic infections or tuberculosis occurred in ustekinumab-treated pts (see table). PBO (n = 209) UST 130 mg (n = 209) UST ∼ 6 mg/kga (n = 209) Clinical responseb Wk 3 45 (21.5) 68 (32.5) p = 0.010 81 (38.8) p < 0.001 Wk 6c 60 (28.7) 108 (51.7) Delta = 23% p < 0.001 116 (55.5) Delta = 26.8% p < 0.001 Wk 8 67 (32.1) 99 (47.4) p < 0.001 121 (57.9) p < 0.001 Clinical remissiond Wk 3 24 (11.5) 33 (15.8) p = 0.199 48 (23.0) p = 0.002 Wk 6 37 (17.7) 60 (28.7) p = 0.007 73 (34.9) p < 0.001 Wk 8 41 (19.6) 64 (30.6) Delta = 11.0% p = 0.009 84 (40.2) Delta = 20.6% p < 0.001 Data are n (%); a weight-range based UST doses ∼6 mg/kg: 260 mg (weight ≤55 kg), 390 mg (weight >55 kg and ≤85 kg), 520 mg (weight >85 kg); b ≥100 pt reduction in CDAI; c primary endpoint; d CDAI < 150. Conclusion: IV UST induced clinical response and remission in pts with moderate-severe CD not previously failing anti-TNFs and was well-tolerated through induction. Disclosure of Interest: B. Feagan Other conflict with: Investigator, Janssen R&D, LLC, C. Gasink Other conflict with: Employee, Janssen R&D, LLC, Y. Lang Other conflict with: Employee, Janssen R&D, LLC, J. Friedman Other conflict with: Employee, Janssen R&D, LLC, J. Johanns Other conflict with: Employee, Janssen R&D, LLC, L.-L. Gao Other conflict with: Employee, Janssen R&D, LLC, B. Sands Other conflict with: Investigator, Janssen R&D, LLC, S. Hanauer Other conflict with: Investigator, Janssen R&D, LLC, P. Rutgeerts Other conflict with: Investigator, Janssen R&D, LLC, S. Targan Other conflict with: Investigator, Janssen R&D, LLC, S. Ghosh Other conflict with: Investigator, Janssen R&D, LLC, W. de Villiers Other conflict with: Investigator, Janssen R&D, LLC, J.-F. Colombel Other conflict with: Investigator, Janssen R&D, LLC, Z. Tulassay Other conflict with: Investigator, Janssen R&D, LLC, U. Seidler Other conflict with: Investigator, Janssen R&D, LLC, W. Sandborn Other conflict with: Investigator, Janssen R&D, LLC. References References 3Sandborn WJ, et al. N Engl J Med 2012; 367: 1519– 1528. CrossrefCASPubMedWeb of Science®Google Scholar OP054-LB5 SUSTAINED EFFICACY AFTER DUAL TOPICAL APPLICATION OF THE TOLL-LIKE RECEPTOR 9 AGONIST DIMS0150 IN CHRONIC ACTIVE ULCERATIVE COLITIS PATIENTS R. Atreya1, F. Scaldaferri2, S. Bloom3, T. E. Knittel4, V. Gerardi5, Å. Karlsson4, J. Kowalski4, M. Lukas6, R. Löfberg7, R. Petryka8, R. Schnabel9, U. Seidler10, S. Nancey11, M. Neurath1 and C. Hawkey12 1 Department of Medicine, University of Erlangen-Nuernberg, Erlangen, Germany 2 Internal Medicine Department/Gastroenterology Division, Catholic University of Rome, Rome, Italy 3 Gastroenterology, University College London Hospital, London, United Kingdom 4 R&D, Index Pharmaceuticals, Stockholm, Sweden 5 Catholic University of Rome, Rome, Italy 6 IBD Clinical and Research Centre, Prague, Prague, Czech Republic 7 Karolinska Institute and Sophiahemmet, Stockholm, Sweden 8 NZOZ Vivamed, Warsaw, Poland 9 Pannonia Maganorvosi Centrum, Budapest, Hungary 10 Dept. of Gastroenterology, Hepatology and Endocrinology, MHH, Hannover, Germany 11 Gastroenterology, Lyon-Sud Hospital, Pierre-Bénite, France 12 Department of Gastroenterology, Nottingham University Hospitals, Nottingham, United Kingdom Contact E-mail Address: thomas.knittel@indexpharma.com Introduction: In the COLLECT study the Toll-like Receptor-9 agonist DIMS0150 was evaluated for its therapeutic efficacy in ulcerative colitis patients refractory to conventional therapy. Patients were followed up to one year after administration of two single topical doses and long term efficacy and sustained clinical effects were analysed in a post-hoc analysis. Aims & Methods: The oligonucleotide DNA based ImmunoModulatory Sequence0150 was studied in a randomised, double blind, placebo-controlled, multicentre, pan-European phase III trial in 131 patients with moderate to severe ulcerative colitis. Patients were randomly assigned to receive two single doses of DNA based ImmunoModulatory Sequence0150 (30 mg) or placebo (in a 2:1 ratio) administered topically via endoscopy to the inflamed mucosa at baseline (week 0) and after 4 weeks (week 4). Efficacy was studied using the endpoints symptomatic remission (SR), absence of blood in stool and mean weekly stools <35) and registration remission (RR), Clinical Activity Index ≤4 and mucosal healing (MH) defined as endoscopic Mayo score of 0 or 1. Results: SR was present in 32.1% of the DNA based ImmunoModulatory Sequence0150 vs 14.0% of the placebo treated patients (p = 0.02) 4 weeks after a single topical administration of DIMS0150. RR was achieved in 21.0% of the DNA based ImmunoModulatory Sequence0150 vs 4.7% of the placebo treated patients (p = 0.02), and MH was present in 34.6% vs 18.6% (p = 0.09), respectively after 4 weeks. Sustained SR at weeks 4 and 12, i.e. SR both at week 4 and week 12, was achieved in 24.7% of the DNA based ImmunoModulatory Sequence0150 vs 11.6% of the placebo treated patients (p = 0.09) and for weeks 4 and 52 it was 13.6% vs 4.7% respectively (p = 0.14). The corresponding results for sustained MH was 27.2% vs 14.0% (p = 0.10) for week 4 and week 12, and 1.2% vs 2.3% for week 4 and week 52. The combined endpoint of SR and MH achieved at both weeks 4 and 12 was 14.8% in the DIMS0150 treated vs 0% in the placebo treated patients (p = 0.008) Sustained RR at weeks 4 and 12 was 14.8% in the DNA based ImmunoModulatory Sequence0150 vs 2.3% in the placebo treated patients (p = 0.06). Conclusion: The COLLECT study demonstrates that dual topical administration of the Toll-like Receptor-9 agonist DNA based ImmunoModulatory Sequence0150 is able to induce sustained clinical effects in chronic active, moderate to severe ulcerative colitis patients even 52 weeks after initial treatment. Disclosure of Interest: R. Atreya Financial support from: Index Pharmaceuticals, Consultancy for: Index Pharmaceuticals, F. Scaldaferri Consultancy for: InDex Pharmaceuticals, S. Bloom Financial support from: Index Pharmaceuticals, T. Knittel Consultancy for: InDex Pharmaceuticals, Shareholder of: InDex Pharmaceuticals, V. Gerardi: None declared, Å. Karlsson Consultancy for: Index Pharmaceuticals, Shareholder of: Index Pharmaceuticals, J. Kowalski Consultancy for: Index Pharmaceuticals, M. Lukas Financial support from: Index Pharmaceuticals, R. Löfberg Consultancy for: Index Pharmaceuticals, Shareholder of: Index Pharmaceuticals, R. Petryka Financial support from: Index Pharmaceuticals, R. Schnabel Financial support from: Index Pharmaceuticals, U. Seidler Financial support from: Index Pharmaceuticals, S. Nancey Financial support from: Index Pharmaceuticals, M. Neurath Consultancy for: Index Pharmaceuticals, C. Hawkey Consultancy for: Index Pharmaceuticals. OP054-LB6 SUSTAINED RESPONSE AFTER FAECAL TRANSPLANTATION IN ULCERATIVE COLITIS IS DRIVEN BY BUTYRATE PRODUCERS C. Ponsioen1, S. Fuentes2, N. Rossen1, G. D. Haens1, E. Zoetendal2, L. Huskonen3 and W. M. de Vos2 1 Gastroenterology & Hepatology, Academic Medical Center, Amsterdam 2 Laboratory of Microbiology, WUR, Wageningen, Netherlands 3 RPU Immunobiology, University of Helsinki, Helsinki, Finland Contact E-mail Address: c.y.ponsioen@amc.uva.nl Introduction: We aimed to identify bacterial signatures that are associated with sustained remission after faecal transplantation for active ulcerative colitis (UC). To this end, we analysed the faecal and mucosal microbiota composition during and up to 3 years post transplantation. Aims & Methods: Faeces and biopsies from UC patients and healthy donors who participated in the TURN trial were analysed. This trial compared the efficacy of two duodenal infusions of faecal homogenates after bowel preparation from a healthy donor or autologous. Microbiota profiles were determined by phylogenetic microarraying and the number of butyryl-coenzyme A (CoA)-CoA transferase genes (ButCoA) was determined by qPCR. Patients were grouped into responders (Rs) and non-responders (NRs) assessed at week 12 and further stratified by sustained remission (SR) and relapse (assessed at ≥1 year follow-up). Results: At baseline, NR showed reduced amounts of groups from the Clostridium cluster XIVa, and significantly higher levels of bacteroidetes as compared to donors. At 12 weeks these differences were retained. Redundancy analysis showed an almost complete separation of sustained remitters and patients that relapsed at the ≥1-year follow-up. SR was highly associated with shift at 12 weeks to a clostridium IV and XIVa enriched signature, including many butyrate producers, while relapse was associated with proteobacteria and bacteroidetes. The level of ButCoA genes and proportion of known butyrate producers were shown to be enriched in responders, most prominently in patients who would achieve SR. Interestingly, when SR patients and relapsers were subdivided in placebo and donor faeces recipients, only those placebo patients who at baseline had a microbiota close to a Clostridium IV and XIVa like signature were able to retain their response, while in donor recipients this was determined by a Clostridium IV/XIVa rich signature of the donor in all cases. No differences were observed in microbiota composition of mucosal biopsies between responders and NR. Conclusion: In UC patients a microbiota signature low in clostridium clusters IV and XIVa and rich in bacteroidetes and proteobacteria is predictive of poor sustained response to FMT, unless they receive a successful engraftment from a clostridium clusters IV and XIVa rich donor. This signature is driven by butyrate producers and durable response is associated with a restoration of the significantly reduced butyrate gene expression at baseline compared with healthy donors. Disclosure of Interest: None declared. References References 4Rossen N. G. et al. Gastroenterology 2015; 149: 110– 118. CrossrefPubMedWeb of Science®Google Scholar OP054-LB7 A MULTI-CENTER, CLUSTER RANDOMIZED DOSE-FINDING STUDY OF FECAL MICROBIOTA TRANSPLANTATION CAPSULES FOR RECURRENT CLOSTRIDIUM DIFFICILE INFECTION M. Fischer1, J. R. Allegretti2, M. Smith3, M. J. Klank1, G. Mendolia3, E. Vo3 and Z. Kassam3 1 Gastroenterology, Indiana University, Indianapolis 2 Gastroenterology, Brigham and Women's Hospital, Boston 3 Openbiome, Medford, United States Contact E-mail Address: jallegretti@partners.org Introduction: Fecal microbiota transplantation (FMT) is a promising therapy for recurrent Clostridium difficile infection (CDI) and FMT capsules have emerged; however, the ideal dose is unknown. Aims & Methods: We aim to evaluate the safety and resolution rate of diarrhea following low and high dose FMT capsules in patients who have suffered three or more recurrences of CDI and failed to maintain CDI cure after standard oral vancomycin therapy. Open-label, cluster dose-finding study performed at two academic hospitals. One site was randomized to low dose FMT capsules (30 pills once) and the other to high dose FMT capsules (30 pills daily for 2 consecutive days). Patients in both groups received oral proton pump inhibitor therapy daily for 48 h prior to FMT to decrease gastric acid and maintain bacterial viability. FMT capsules were generated from healthy, rigorously screened unrelated donors from a universal stool bank (mean age: 26 years, mean body mass index: 22.2 kg/m2, mean waist circumference: 32.5 in, donors pooled clinical success in CDI: 81.3%, n = 48, universal stool bank pooled clinical success in CDI: 85.2%, n = 861) using a scalable, physically stable (>30 days at 25o C) emulsion-based production protocol. The primary end points were safety assessed grade 2 or above, and clinical resolution of diarrhea with no recurrence at 8-week follow-up as per guidelines. Safety data was compared between high and low FMT dose groups by review of adverse events. Non-responders were treated with high dose FMT capsules (30 pills daily for 2 consecutive days) in either arm. Results: Baseline characteristics of the 17 patients were similar (Figure 1). No adverse events or serious adverse events attributed to FMT were observed with either the high or low FMT dose. Resolution of diarrhea in the high dose was achieved in 5/7 (71%) patients and in 7/10 (70%) patients that received low dose FMT at 8-week follow-up (p = 0.33). Resolution of diarrhea was assessed at multiple time intervals. Clinical remission at 72 h was achieved in 7/7 in the high dose and 8/10 in the low dose (p = 0.56). All five of the non-responders were treated with a high dose FMT extension. Four out of these five patients (80%) had resolution of diarrhea. Overall, the aggregate capsule response rate was 16/17 (94%). The one patient who failed capsule extension was cured with FMT by colonoscopy. Conclusion: To our knowledge, this study is the first randomized study of FMT capsules in recurrent CDI and provides insight into the lowest, safe, effective FMT capsule dose. Disclosure of Interest: None declared. High Dose FMT Capsules (n=7) Low Dose FMT Capsules (n=10) p-value Age – Mean ± SD 60.8 ± 16.8 57.7 ± 20.2 0.73 Female – n (%) 5 (71%) 8 (80%) 0.39 Number of recurrences – Mean ± SD 3.85 ± 0.89 3.4 ± 0.51 0.25 Prior antibiotics – n (%) 7 (100%) 9 (90%) 0.58 Health-care acquired Clostridium difficile infection – n (%) 1 (14.2%) 5 (50%) 0.14 OP103-LB1 THE NATIONAL COLORECTAL CANCER FIT-BASED SCREENING PROGRAMME OF THE NETHERLANDS: OUTCOMES OF THE FIRST YEAR E. Toes-Zoutendijk1, M. E. van Leerdam2, F. van Hees1, E. Dekker3, M. P. van der Meulen1, H. van Vuuren4, E. J. Kuipers4, H. Bonfrer2, F. van Kemenade5, K. Biermann5, M. Thomeer6, M. C. Spaander4, H. Veldhuizen7, S. Kroep1, M. van Ballegooijen1, H. de Koning1 and I. Lansdorp-Vogelaar1 1 Public Health, Erasmus MC, University Medical Center, Rotterdam 2 Antoni van Leeuwenhoek, Dutch Cancer Institute 3 Gastroenterology and Hepatology, Academic Medical Center, Amsterdam 4 Gastroenterology and Hepatology 5 Pathology 6 Radiology 7 Quality improvement, Erasmus MC, University Medical Center, Rotterdam, Netherlands Contact E-mail Address: e.toes-zoutendijk@erasmusmc.nl Introduction: In 2014, a national program for colorectal cancer (CRC) screening with biennial faecal immunochemical testing (FIT) using the FOB-Gold (Sentinel, Italy) was initiated in the Netherlands. The programme was preceded by a period of planning, piloting and implementation of monitoring system. Aims & Methods: To illustrate the importance of planning and monitoring of screening programmes based on the outcomes of the first year of the Dutch national CRC screening programme. Individuals in the target population received a FIT. Participants with a positive test received an appointment for colonoscopy. Participation and positivity rates, positive predictive values (PPVs) and detection rates per 1000 participants were determined, using data from the national information system for the CRC Screening Program (ScreenIT). Results: From the 741,916 persons invited, 529,056 (71.3%, 95% confidence interval (CI): 71.2–71.4%) participated in the national programme. The age-adjusted positivity rate in the first half year of 9.6% (95% CI: 9.5–9.8%) at 15 µg Hb/g faeces was higher than anticipated. Age-adjusted detection rates for CRC and advanced adenomas (AADs) were also higher, 5.6 (95% CI: 5.3–6.0) and 28.5 (95% CI: 27.7–29.4) per 1000 respectively, but the PPV of advanced neoplasia (CRC or AAD) was lower, 42.9% (95% CI: 41.7–44.1%). To accommodate available colonoscopy capacity and balance benefits and harms of screening, the cut-off was increased to 47 µg Hb/g faeces in July 2014. This resulted in an age-adjusted positivity rate of 6.9% (95% CI: 6.8