W. Sandborn

P501 Effects of continued vedolizumab therapy for ulcerative colitis in week 6 induction therapy nonresponders

Background: Vedolizumab (VDZ), a gut-selective, humanized, anti-α4β7 integrin monoclonal antibody, was evaluated for the treatment of ulcerative colitis (UC) in the 52-week GEMINI 1 trial. In this study, 47.1% of patients had a clinical response to VDZ induction therapy at week 6. Here the efficacy of continuing VDZ therapy is evaluated in week 6 nonresponders to VDZ induction therapy. Methods: GEMINI 1 participants were randomly assigned to receive placebo (PBO) or VDZ 300 mg (cohort 1) or assigned to receive open-label VDZ (cohort 2) intravenously at weeks 0 and 2. Patients who did not respond to VDZ induction therapy at week 6 received open-label VDZ every 4 weeks (Q4W) during maintenance, whereas all PBO patients continued on PBO. Clinical response (reduction in partial Mayo Clinic score [MCS] of ≥2 points and decrease of ≥25% from the baseline score, with an accompanying reduction in rectal bleeding subscore of ≥1 point or a rectal bleeding subscore of 0 or 1) and clinical remission (partial MCS of ≤2 points and no subscore >1 point) were assessed in week 6 nonresponders at weeks 10 and 14 (prespecified) and at week 52 (post hoc). Week 52 post hoc analyses were also performed for mucosal healing (Mayo Clinic scale endoscopic subscore of 0 or 1) in week 6 nonresponders and for efficacy end points in week 6 nonresponders who had clinical response at week 10 or 14. Results: At baseline, the median duration of UC in VDZ week 6 nonresponders (4.6 years) was comparable to week 6 responders. Baseline UC activity (ie, complete MCS) was higher in VDZ week 6 nonresponders (median, 9.0) than inweek 6 responders (median, 8.0), whichwas attributable mainly to a greater proportion of patients withMCS of 9 to 12 (56% of week 6 nonresponders, 42% of week 6 responders). Rate of previous tumor necrosis factor antagonist failure was higher among week 6 nonresponders (51%) than among week 6 responders (32%). Proportions of week 6 nonresponders who had clinical response, clinical remission, or mucosal healing at weeks 10, 14, and 52 were numerically greater with VDZ than with PBO (Table). These differences were most pronounced at week 52. For both VDZ and PBO, the proportions of week 6 nonresponders who had clinical response, clinical remission, or mucosal healing at week 52 were similar between those who responded at week 10 and those who responded at week 14; the small numbers of PBO-treated patients in these subgroups are a limitation of this analysis. Conclusions: Patients with UC who did not have a clinical response to VDZ induction therapy at week 6 and continued VDZ Q4W had higher rates of clinical response and remission at weeks 10, 14, and 52 and of mucosal healing at week 52 than did those who received PBO.

P150 Responsiveness of endoscopic indices in the evaluation of ulcerative colitis

was 36.4±15.6 years. Disease duration was 7.0±6.4 years. The disease locations were 53 cases of pancolitis (73.6%), and 16 cases of left-sided colitis (27.2%). The clinical courses were 51 cases of relapse and remission (70.8%), 15 cases of chronically active colitis (20.8%), and 6 cases of fulminant or initial severe attack (8.4%). In terms of post-colectomy complication, there were 14 cases of intra-abdominal abscess, 13 cases of bowel obstruction, 8 cases of wound infection, 4 cases of bleeding and 2 cases of anastomotic leak (including overlapping cases). In emergency situations, 16 patients (22.2%) underwent colectomy due to toxic megacolon, severe bleeding, and perforation. Between emergency surgery (group A, n = 16) and elective surgery (group B, n = 56), there was no statistically significant difference in terms of the occurrence of complications [group A: 7/16 (43.6%), group B: 19/56 (33.9%)]. The analysis of risk factors for post-colectomy complications with univariate and multivariate studies was respectively performed in both groups. In group A, there was no significant factor. In group B, 7 years disease duration (OR: 6.65, 95%CI: 1.79 24.73), and >200mg/week preoperative prednisone use (OR: 9.80, 95%CI: 2.50 38.41) were statistically significant. Conclusions: The factors that correlated with an increased risk of post-colectomy complications in patients with UC were young onset ( 7 years), and a significant amount of preoperative prednisone use (>200mg/ week). To prevent such complications, we should treat these patients carefully.

OP024 Agreement among central readers in the evaluation of endoscopic disease activity in Crohn's disease

of a biomarker test that can identify and stratify young IBD patients. Methods Samples from well-characterized patients were collected from 15 North American GI centers. Median age was 15 (IQR: 13-16). Samples from 251 patients were used: 147 Crohns disease (CD), 47 ulcerative colitis (UC) and 57 non-IBD disease controls. A combination of serological markers (ASCA-IgA, ASCA-IgG, ANCA, pANCA, anti-OmpC, anti-Fla2, anti-FlaX and anti-CBir1), four gene variants (ATG16L1, NKX2-3, ECM1, and STAT3) and five inflammatory markers (CRP, SAA, ICAM, VCAM, and VEGF) were used in this evaluation. Identification of IBD, CD, and UC and was made with the aid of a machine learning model. Sensitivity, specificity, NPV, PPV and accuracy statistics were calculated for both the IBD vs. Non-IBD component of the diagnostic model, and separately for the CD vs. UC component (for patients called IBD by the model). Results The multi-marker biomarker diagnostic model performed in classifying IBD, CD and UC in pediatric patients as reported in Table 1. We observed a sensitivity of 86.1% and a specificity of 86% for identifying young adults with IBD. The sensitivity and specificity for classifying CD in patients called IBD by the model was 91.9% and 75.8%, respectively. UC sensitivity and specificity was 82.1% and 90.5%, respectively. Diagnostic accuracy of the biomarkers was 86.1% for IBD vs. non-IBD, 88.2% for CD and 88.9% for UC. The IBD NPV and PPV were 64.5% and 95.4% respectively. CD NPV and PPV were 73.5% and 92.7%, respectively. UC NPV and PPV were and 95.5% and 67.6%, respectively. Conclusion Our results demonstrate that a combination of serological, genetic, and inflammatory markers may be utilized for classifying non-IBD, CD, and UC in the young adult patient population. Further studies are required to further investigate the clinical utility of this biomarker test. Table 1

P176 Patient reported outcome measures derived from the Crohn's Disease Activity Index: Correlation between PRO2 and PRO3 scores and CDAI-defined clinical thresholds

of life, little is known about their satisfaction with clinical management, or with associated drug treatment. Knowing the perception and satisfaction that patients have about the management of their disease, it will allow designing strategies aimed to improve patients’ quality of life and promoting adherence and treatment effectiveness. The aim of this study is to understand perceptions, attitudes, experiences, and satisfaction with clinical management of UC patients, particularly in aspects related to treatment. Methods: A discussion group was performed with eight UC patients in remission who had not received biologics or corticosteroids during the previous year. The heterogeneity was ensured by selecting different UC profiles using the following variables: severity, time since onset, follow-up level of care, currently on treatment, managed by a UC care unit, patients belonging to any patient association and gender. Following qualitative methodology a descriptive-interpretative content analysis was performed to detect emerging categories, building an explanatory framework. Results: The most frequent mentions are related to diagnostic process, follow-up and treatment. Diagnostic delay was detected due to lack of clinical suspicion from primary care (PC) and delayed diagnostic tests. Patients prefer to receive care on demand, channeled through remote care, which helps to resolve questions about UC, issues with treatment, or when a relapse occurs, and minimizes visits to the hospital. Patients with moderate UC diagnosis perceive some training lacks in PC physicians about management of symptoms, although, in general, they declare their satisfaction with follow-up both in PC and specialist care. When forced to go to the emergency room, they are quite dissatisfied with management, due to the delay in providing symptoms resolution, mainly related to inadequate knowledge of UC management. To avoid this, patients suggest the possibility of receiving care on demand from a specialist in UC. In relation to treatment, patients expect it to be effective, reducing symptoms. Secondly, treatment should be safe, minimizing short and long-term side effects. Regarding to treatment characteristics that patients would like to improve, they mention a reduction in the number of doses and tablets per day, and an increased number of tablets per box. Conclusions: These results suggest the importance of developing strategies to facilitate care on demand, remote care, and to investigate on effective and safe treatments to improve patients’ quality of life. P176 Patient reported outcome measures derived from the Crohn’s Disease Activity Index: Correlation between PRO2 and PRO3 scores and CDAI-defined clinical thresholds R. Khanna1, G. D’Haens1,2, B.G. Feagan1,3, W.J. Sandborn1,4, M.K. Vandervoort1, G. Zou1, R.L. Rolleri5, E. Bortey5, B.G. Levesque1,4 *. 1Robarts Clinical Trials Inc., Robarts Research Institute, Western University, London, Ontario, Canada, 2University of Amsterdam, Academic Medical Center, Amsterdam, Netherlands, 3Western University, Department of Epidemiology and Biostatistics, Department of Medicine, London Ontario, Canada, 4University of California, San Diego, Division of Gastroenterology, La Jolla, United States, 5Salix Pharmaceuticals Inc., Clinical Development, Raleigh North Carolina, United States

DOP073 Efficacy of induction treatment with vedolizumab for patients with Crohn's disease who have experienced tumour necrosis factor antagonist failure or are tumour necrosis factor antagonist naive

W.J. Sandborn1, P. Rutgeerts2 *, J. Xu3, B. Abhyankar4, I. Fox5. 1University of California San Diego, Division of Gastroenterology, La Jolla, United States, 2Katholieke Universiteit and University Hospital Gasthuisberg, Division of Gastroenterology, Leuven, Belgium, 3Takeda Pharmaceuticals International Company, Biostatistics, Cambridge, United States, 4Takeda Development Centre (Europe) Ltd, Clinical Science, London, United Kingdom, 5Takeda Pharmaceuticals International Company, Clinical Development, Cambridge, United States

P552 Association between Week 8 Mayo subscores and hospitalisation rates in adalimumab-treated patients with ulcerative colitis from ULTRA 1 and ULTRA 2

P552 Association between Week 8 Mayo subscores and hospitalisation rates in adalimumab-treated patients with ulcerative colitis from ULTRA 1 and ULTRA 2 W. Reinisch1 *, W.J. Sandborn2, B. Feagan3, S. Ghosh4, A. Robinson5, M. Skup5, J. Petersson5, B. Huang5, A. Lazar6, R. Thakkar5. 1McMaster University, Department of Medicine, Hamilton, Canada, 2University of California San Diego, Division of Gastroenterology, La Jolla, United States, 3Robarts Clinical Trials Inc., Robarts Research Institute, Western University, London, Ontario, Canada, 4University of Calgary, Department of Medicine, Calgary, Canada, 5AbbVie Inc, GPRD, North Chicago, United States, 6AbbVie Deutschland GmbH & Co, KG, GPRD, Ludwigshafen, Germany

P209 Long-term effectiveness and safety of vedolizumab in patients with ulcerative colitis: 5-year cumulative exposure of GEMINI 1 completers rolling into the GEMINI open-label extension study

P209 – Table 1. Effectiveness outcomes in patients with UC and cumulative VDZ exposure for up to 248 wks W. Sandborn5, B. Sands6, S. Danese7, G. D’Haens8, A. Kaser9, R. Panaccione10, D. Rubin11, I. Shafran12, S. O’Byrne13, P. Geransar13, A. James14, A. Kaviya15, J.M. Khalid16 1Mayo Clinic College of Medicine, Gastroenterology and Hepatology, Rochester, United States; 2Icahn School of Medicine at Mount Sinai, Gastroenterology, New York, United States; 3Robarts Research Institute, University of Western Ontario, Robarts Clinical Trials, London, Canada; 4University hospitals Leuven, Department of clinical and experimental medicine, Leuven, Belgium; 5University of California San Diego, Division of Gastroenterology, La Jolla, United States; 6Icahn School of Medicine at Mount Sinai, Division of Gastroenterology, New York, United States; 7Humanitas University, Italy, Gastrointestinal Immunopathology, Milan, Italy; 8Academic Medical Centre, Dept. of Gastroenterology, Amsterdam, Netherlands; 9University of Cambridge, Division of Gastroenterology and Hepatology, Cambridge, United Kingdom; 10University of Calgary, Department of Medicine, Calgary, Canada; 11University of Chicago Medicine Inflammatory Bowel Disease Center, Section of Gastroenterology, Hepatology, and Nutrition, Chicago, United States; 12Shafran Gastroenterology Research center, Gastroenterology, Winter Park, United States; 13Takeda Pharmaceuticals International AG, Global Medical Affairs, Zurich, Switzerland; 14Takeda Development Centre Europe Ltd, Global Statistics and Statistical Programming, London, United Kingdom; 15Takeda Development Centre Europe Ltd, Clinical Development, London, United Kingdom; 16Takeda Development Centre Europe Ltd, Evidence and Value Generation, London, United Kingdom Background: Approval of vedolizumab (VDZ) for moderately to severely active ulcerative colitis (UC) was based on the phase 3 GEMINI 1 study. [1] The GEMINI open-label extension (OLE) trial is an ongoing study investigating the long-term safety of VDZ (NCT00790933). Here we report the 5-year exploratory analyses of effectiveness and safety in patients (pts) with UC who had completed GEMINI 1 and were enrolled in GEMINI OLE. Methods: Analyses included pts who responded to VDZ induction at Week (Wk) 6 and had received VDZ maintenance (every 8 or 4 wks; data were combined) to Wk 52 of GEMINI 1, followed by VDZ every 4 wks in GEMINI OLE. Pts with 248 wks of cumulative VDZ treatment (data were collected from 22 May 2009 to 21 May 2015) were assessed for clinical response (decrease in partial Mayo Score Abstracts of the 12th Congress of ECCO – European Crohn’s and Colitis Organisation S183s of the 12th Congress of ECCO – European Crohn’s and Colitis Organisation S183 [PMS] of ≥2 points and ≥25% change from baseline [BL], with an accompanying decrease in rectal bleeding subscore of ≥1 point from BL or absolute rectal bleeding subscore of ≤1 point), clinical remission (PMS of ≤2 with no individual subscore >1) and health-related quality of life (HRQoL), including IBD Questionnaire (IBDQ) and Euro Quality of Life-5D visual analogue scale (EQ-5D VAS). Safety was also assessed. Results: Of 247 pts in GEMINI 1 who responded to VDZ induction at Wk 6 and received VDZ in maintenance, 154 (62%) completed VDZ maintenance and were enrolled in GEMINI OLE (anti-TNFαnaïve n=107; anti-TNFα failure n=42). At the time of this analysis, 63 pts had completed 248 wks of cumulative VDZ treatment; 54 had discontinued (n=19 [35%] due to lack of continued benefit) and 37 are ongoing (have not yet reached 248 wks of treatment). Of pts with data at Wk 248 (n=63), 98% had clinical response and 90% were in remission (Table). HRQoL improvements were observed at Wk 248, with mean change from BL IBDQ and EQ-5D-VAS scores of 58.7 and 24.0, respectively. In the safety population, 137 pts had adverse (AEs); 17 discontinued due to AEs. Serious AEs were reported in 44 pts (in 7 pts these were drug-related; 8 pts discontinued as a consequence of serious AEs). No deaths were reported. Conclusions: In UC patients who were responders at Wk 6 of GEMINI 1 (who continued to respond during the study), long-term VDZ therapy (∼5 years) was associated with clinical benefits including clinical response, clinical remission and HRQoL improvements. The safety profile was consistent with that previously observed in a 3year interim analysis of the OLE study. References: [1] Feagan BG, Rutgeerts P, Sands BE, et al. (2013), Vedolizumab as Induction and Maintenance Therapy for Ulcerative Colitis, N Engl J Med, 699–710 P210 The associations of optimism, social support, and coping strategies with health-related quality of life in a cohort of patients after proctocolectomy with ileal Pouch-anal anastomosis I. Cohen*1, Y. Benyamini2, H. Tulchinsky3, I. Dotan1 1Tel Aviv Sourasky Medical Center, affiliated to Sackler Faculty of Medicine, Tel Aviv University, Department of Gastroenterology and Liver Diseases, Tel-Aviv, Israel; 2Tel Aviv University, Bob Shapell School of Social Work, Tel-Aviv, Israel; 3Tel Aviv Sourasky Medical Center, affiliated to Sackler Faculty of Medicine, Proctology Unit, Department of Surgery, Tel-Aviv, Israel Background: Inflammatory bowel diseases (IBD) are associated with reduced health-related quality of life (HRQoL). We aimed to identify factors that influence patients HRQoL by exploring the role of optimism, social support and coping strategies in contributing to patients’ HRQoL. We focused on patients with ulcerative colitis (UC) after pouch surgery representing a distinct population which is followed up in a dedicated referral clinic. Methods: Patients were recruited at the Comprehensive Pouch Clinic and completed six questionnaires: demographics, HRQoL (IBDQ), dispositional optimism (revised Life Orientation Test, LOT-R), social support inventory (ENRICHD), Coping strategies (brief COPE), and illness acceptance (DDAQ). Pouch behavior was determined clinically and defined as normal pouch (NP) or pouchitis. Results: A total of 151 pouch patients were recruited: 75 (50%) females, average age 47.91±15.51 years, average age of UC diagnosis 27.11±13.53 years, mean time since pouch surgery 10.03±8.09 years. At the time of recruitment 48 (32%) had NP. Women had lower HRQoL than man (p=0.04), education level was correlated with HRQoL (r=0.27, p=0.001), age at diagnosis was negatively correlated to HRQoL (r=−0.19, p=0.02). Optimism was associated with higher HRQoL (R=0.40. p<0.001). Pessimism was associated to older age at diagnosis (r=0.23, p=0.01) and to lower education level (r=−0.20, p=0.02). Optimists and pessimists differed in the manner they cope with disease – optimists used more positive reframing and tended to find alternative meaningful activities, while pessimists tended to use self-blame, behavioral and mental disengagement. Furthermore, optimists reported better social support (r=0.29, p=0.00). Social support was also associated with higher HRQoL (R=0.40. p<0.001). Patients with pouchitis had lower HRQoL and social support (all p<0.01 compared to NP) but did not differ in the level of optimism. Predictors of HRQoL in the multivariate Hierarchical Regression analysis were gender (β=−0.12; p<0.05), educational level (β=0.22; p<0.001), social support (β=0.12; p<0.05) and coping strategies: behavioral disengagement (β=−0.19; p=0.05), mental disengagement (β=−0.22; p<0.001), activities engagement (β=0.29; p<0.001), and symptom tolerance (β=0.19; p=0.05). Conclusions: Factors affecting HRQoL levels in UC pouch patients are Gender, education level, age at disease diagnosis and pouch behavior. Dispositional optimism, social support and coping strategies play significant role in patients HRQoL. P211 Differences in therapeutic approaches and outcomes in paediatric and adult onset Crohn’s disease with perianal fistula: comparison of 2 multicentre fistula cohorts S. Sebastian*1,2, C. Black2, M.V. Nair1,3, T. Drskova4, O. Hradsky4, C. Tzivinikos5, K. Sahnan6, R. Muhammed7, D. Devadason8, R.S. Parmar5, K. Crook6, A. Akbar6, M. Thomson3, D. Pugliese9, A. Armuzzi9, K.H. Katsanos10, D.K. Christodoulou10, C. Selinger11, G. Maconi12, G. Fiorino13, U. Kopylov14, M.M. Bosca-Watts15, K. Karmiris16, P. Ellul17, S. Ben-Horin14, S. Danese13, A.L. Hart6 1Hull & East Yorkshire NHS Trust, Hull, United Kingdom; 2Hull & East Yorkshire NHS Trust, IBD Unit, Hull, United Kingdom; 3Sheffied Children’s Hospitals NHS Foundation Trust, Sheffiled, United Kingdom; 4Motol University Hospital, Prague, Czech Republic; 5Alder Hey Children’s Hospital, Liverpool, United Kingdom; 6St Marks Hospital, London, United Kingdom; 7Birmingham Children’s Hospital, Birmingham, United Kingdom; 8Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom; 9Gemelli Hospital Catholic University, Rome, Italy; 10University of Ioannina, Ioannina, Greece; 11Leeds Teaching hospitals NHS Trust, Leeds, United Kingdom; 12Louigi Sacco University Hospital, Milan, Italy; 13Humanitas Research Hospital, Milan, Italy; 14Sheba Medical Center, Tel-Aviv, Israel; 15University Clinic Hospital, Valencia, Spain; 16Venizeleio General Hospital, Crete, Greece; 17Mater Dei Hospital,

P257 Importance of deep remission compared with mucosal healing only: Results from EXTEND

UC patients were still in remission one year after discontinuing IFX (Figure). Fifty percent of the patients were still in remission after median 680 [412 948] and 1334 [995 1673] days, respectively, p = 0.057. Univariate analyses indicated an association of longer disease duration with relapse in CD, OR 1.1 [1.0 1.1], p = 0.022; but this was not confirmed in multivariate analyses. Twenty-four of 25 CD patients (96%), and 5 of 7 UC patients (71%) experienced complete clinical remission at retreatment with IFX after relapse. Conclusions: Most IBD patients who discontinued IFX while in clinical remission later experienced relapse, with a nonsignificant trend towards a better prognosis in patients with UC. Retreatment with IFX at relapse in this particular subpopulation was followed by higher remission rates than expected from clinical trials.

Looking beyond symptoms and disease activity to define disease severity in inflammatory bowel disease: results of an IOIBD specialist panel

Looking beyond symptoms and disease activity to define disease severity in inflammatory bowel disease : results of an IOIBD specialist panel

DOP059 Reduction of fecal calprotectin levels and relationship to clinical parameters in the phase 2 study of laquinimod for the treatment of active moderate to severe Crohn's disease

DOP059 Reduction of fecal calprotectin levels and relationship to clinical parameters in the phase 2 study of laquinimod for the treatment of active moderate to severe Crohn’s disease G. D’Haens1 *, W.J. Sandborn2, P. Rutgeerts3, J.F. Colombel4, K. Brown5, A. Haviv6, H. Barkay7, A. Sakov7, B. Feagan8. 1University of Amsterdam, Academic Medical Center, Amsterdam, Netherlands, 2University of California, UCSD Inflammatory Bowel Disease Center, San Diego CA, United States, 3Catholic University of Leuven, Department of Internal Medicine and Endoscopy, Leuven, Belgium, 4Icahn School of Medicine at Mount Sinai, Gastroenterology, New York, United States, 5Teva Pharmaceuticals, Clinical Development Research and Development, Frazer, United States, 6Chiasma Pharm, Formerly of Teva Pharmaceuticals, Jerusalem, Israel, 7Teva Pharmaceuticals, Biostatistics Research and Development, Netanya, Israel, 8University of Western Ontario, Robarts Clinical Trials Robarts Research Institute, Ontario, Canada