Parnia Geransar

Effect of Vedolizumab Treatment on Extraintestinal Manifestations in Patients with Crohn’s Disease: A Gemini 2 Post hoc Analysis

Introduction Reported rates of extraintestinal manifestations (EIMs) in patients (pts) with Crohn’s disease (CD) are 37%–55%. 1,2 This post hoc exploratory analysis investigated the effect of vedolizumab (VDZ) treatment on existing and new EIMs in patients with CD enrolled in GEMINI 2 (NCT00783692). Method Outcomes were sustained resolution of existing EIMs (absence of symptoms, sustained to study end), worsening of existing EIMs and occurrence of new EIMs. For arthritis/arthralgia (ar/ar), Kaplan–Meier estimates were used to describe ‘time to sustained resolution’. A multivariate Cox regression adjusting for confounding factors was conducted. The effect of steroid tapering on new or worsening ar/ar was explored, using prednisone equivalent dose (≤30 mg) as a time-dependent covariate. Results Pts received VDZ (n=814), VDZ/placebo (VDZ/PLA: VDZ to Week 6, PLA Weeks 6–52; n=153) or PLA only (n=148). Rates of EIMs other than ar/ar were too low for further analysis. Predicted annual rates of sustained resolution of ar/ar were 51% (VDZ), 41% (VDZ/PLA) and 36% (PLA). VDZ pts were 32% more likely to achieve sustained resolution of ar/ar versus PLA pts, and 21% less likely to have a worsening/new occurrence (Table, both non-significant [NS]). In pts receiving corticosteroids (CS; n=530), adjustment for CS withdrawal resulted in an ~4% increased likelihood of new or worsening ar/ar in all groups (30 mg dose reduction hazard ratio [HR] 1.04 [95% CI: 0.67–1.60], NS). Hazard reduction for the VDZ groups versus PLA was similar (VDZ, 0.73 [95% CI: 0.44–1.22], NS; VDZ/PLA, 0.72 [95% CI: 0.37–1.39], NS). Conclusion In this post hoc exploratory analysis, there were trends for both a reduced incidence of new or worsening ar/ar and an increased rate of sustained resolution of ar/ar in pts receiving VDZ. CS tapering increased the probability of ar/ar in all groups. References . Lakatos L, et al. World J Gastroenterol2003;9:2300 . Zippi M, et al. World J Gastroenterol2014;20:17463 Disclosure of Interest B. Feagan Conflict with: Abbott/AbbVie, Amgen, Astra Zeneca, Bristol-Myers Squibb (BMS), Janssen Biotech (Centocor), JnJ/Janssen, Roche/Genentech, Millennium, Pfizer, Receptos, Santarus, Sanofi, Tillotts, UCB Pharma, Conflict with: Abbott/AbbVie, ActoGeniX, Akros, Albireo Pharma, Amgen, Astra Zeneca, Avaxia Biologics Inc., Avir Pharma, Axcan, Baxter Healthcare Corp., Biogen Idec, Boehringer-Ingelheim, Bristol-Myers Squibb, Calypso Biotech, Celgene, Elan/Biogen, enGene, Ferring Pharma, Roche/Genentech, gICare Pharma, Gilead, Given Imaging Inc., GSK, Ironwood Pharma, Janssen Biotech (Centocor), JnJ/Janssen, Kyowa Hakko Kirin Co Ltd., Lexicon, Lilly, Lycera BioTech, Merck, Mesoblast Pharma, Millennium, Nektar, Nestles, Novo Nordisk, Pfizer, Prometheus Therapeutics and Diagnostics, Protagonist, Receptos, Salix Pharma, Serono, Shire, Sigmoid Pharma, Synergy Pharma Inc., Takeda, Teva Pharma, TiGenix, Tillotts, UCB Pharma, Vertex Pharma, VHsquared Ltd., Warner Chilcott, Wyeth, Zealand, Zyngenia, Conflict with: Director of Robarts Clinical Trials Inc.; member of advisory boards Abbott/AbbVie, Amgen, Astra Zeneca, Avaxia Biologics Inc., Bristol-Myers Squibb, Celgene, Centocor Inc., Elan/Biogen, Ferring, JnJ/Janssen, Merck, Nestles, Novartis, Novo Nordisk, Pfizer, Prometheus Laboratories, Protagonist, Salix Pharma, Takeda, Teva, TiGenix, Tillotts Pharma AG, UCB Pharma, W Sandborn Conflict with: Janssen, AbbVie, Pfizer, Amgen, Genentech, Conflict with: Janssen, AbbVie, Pfizer, Amgen, Genentech, Takeda, Conflict with: Lecture fee(s): AbbVie, Takeda, J.-F. Colombel Conflict with: Intestinal Biotech Development, Genfit, Conflict with: AbbVie, Janssen and Janssen, Genentech, Takeda, Conflict with: AbbVie, Amgen, Boehringer-Ingelheim, Celgene Corporation, Celltrion, Enterome, Ferring, Genentech, Janssen and Janssen, Medimmune, Merck and Co., Pfizer, Protagonist, Second Genome, Seres, Takeda, Theradiag, Conflict with: Lecture fee(s): AbbVie, Ferring, Takeda, Shire, S O’Byrne Conflict with: Takeda Pharmaceuticals International AG, J Khalid Conflict with: Takeda Development Centre Europe Ltd, N Brayshaw Conflict with: Takeda Development Centre Europe Ltd, P Geransar Conflict with: Takeda Pharmaceuticals International AG, D Rubin Conflict with: AbbVie Inc., Bristol-Myers Squibb, Centocor/Janssen Pharmaceuticals, Inc., Cornerstones Health, Inc., Elan Pharmaceuticals, Emmi, Given Imaging, Ironwood, Lifecore Biomedical, LLC, Prometheus Pharmaceuticals, Santarus, Shire, Takeda-Millennium, Telsar Pharmaceuticals, UCB Pharma, Vertex Pharmaceuticals, Warner Chilcott

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,

Long-Term Effectiveness and Safety of Vedolizumab in Patients with Crohn’s Disease: 5-Year Cumulative Exposure of Gemini 2 Completers Rolling Into the Gemini Open-Label Extension Study

Introduction Vedolizumab (VDZ), a gut-selective humanised monoclonal antibody that targets α4β7 integrin, is approved for moderately to severely active Crohn’s disease and ulcerative colitis (UC). The ongoing GEMINI open-label extension (OLE) trial is investigating the long-term safety of VDZ (NCT00790933). We report 5 year exploratory interim analyses of effectiveness and safety in patients (pts) with UC who completed GEMINI 1 and enrolled in GEMINI OLE. Method Pts who responded to VDZ induction at Week (Wk) 6 received VDZ maintenance (every 8 or 4wks) to Wk 52 of GEMINI 1 and VDZ every 4 wks in GEMINI OLE. In an interim analysis, pts with 248 wks of cumulative VDZ (22 May 2009 to 21 May 2015) were assessed for clinical response (decrease in partial Mayo Score [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), health-related quality of life (HRQoL) and safety. Results Of 154 pts (anti-tumour necrosis factor-alpha: naive n=107, failure n=42), 63 had 248 wks’ cumulative VDZ treatment, 54 discontinued (n=19 [35%] due to lack of continued benefit) and a further 37 (24%) had not yet reached 248 wks at data cut-off. Of pts with Wk 248 data, 98% had clinical response and 90% were in remission. HRQoL was improved at Wk 248, with mean change from BL in the Inflammatory Bowel Disease Questionnaire and Euro Quality of Life-5D visual analogue scale scores of 58.7 and 24.0, respectively. At Wk 248, 142 pts had adverse events (AEs), of which 16 discontinued and 46 experienced a serious AE (drug-related n=7; 8 pts discontinued; no deaths). Abstract AODWE-002 Table 1 Effectiveness of long-term VDZ in pts with UC Conclusion Continued clinical response, remission and HRQoL improvements were observed throughout 248 wks (~5 years) of cumulative VDZ therapy in pts with UC who responded at Wk 6, completed GEMINI 1 and enrolled in the OLE. The long-term safety profile of VDZ was consistent with that reported in previous studies. Disclosure of Interest A Kaser Conflict with: Boehringer Ingelheim, Eisai, Ferring, Genentech, GlaxoSmithKline, Hospira, Janssen J and J, Kymab, Second Genome, Shire, VHsquared, Conflict with: Lecture fee(s): Falk, Ferring, Takeda; serves as course director of the Cambridge – MedImmune PhD programme

Incidence of Arthritis/Arthralgia in Inflammatory Bowel Disease with Long-term Vedolizumab Treatment: Post Hoc Analyses of the GEMINI Trials

Abstract Background and Aims Extraintestinal manifestations [EIMs] such as arthritis/arthralgia are common in inflammatory bowel disease. We performed post hoc analyses of data from the GEMINI studies to evaluate the effect of vedolizumab, a gut-selective anti-trafficking agent, on arthritis/arthralgia. Methods Sustained resolution of baseline arthritis/arthralgia, worsening of baseline arthritis/arthralgia, the occurrence of new arthritis/arthralgia, and the composite of new/worsening arthritis/arthralgia were evaluated. Cox modelling was used for time-to-event analysis. The influence of corticosteroid-tapering was also investigated. Results In Crohn’s disease [CD] patients, vedolizumab was significantly less likely than placebo to be associated with new/worsening arthritis/arthralgia (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.44–0.89). Similar incidences of sustained resolution of arthritis/arthralgia occurred with vedolizumab and placebo. In CD patients on corticosteroids at baseline, a decrease in corticosteroid dose increased the risk of new/worsening arthritis/arthralgia (odds ratio [OR], 7.49; 95% CI, 3.50–15.97) regardless of treatment; and in those achieving corticosteroid-free status, arthritis/arthralgia was less likely with vedolizumab than with placebo [HR, 0.14; 95% CI, 0.05–0.35]. In ulcerative colitis [UC] patients, vedolizumab and placebo showed a similar incidence of new/worsening of arthritis/arthralgia. In UC patients on corticosteroid at baseline, arthritis/arthralgia was more likely in those achieving corticosteroid-free status than in those continuing corticosteroids (HR 2.63 [95% CI 1.13–6.11]); and in those achieving corticosteroid-free status, the incidence of arthritis/arthralgia was similar with vedolizumab and placebo. Conclusions Vedolizumab therapy was associated with a reduced likelihood of new/worsening arthritis/arthralgia in CD and no increased incidence of these events in UC. Studies included [ClincialTrials.gov, number] GEMINI 1 [NCT00783718]; GEMINI 2 [NCT00783692]; GEMINI 3 [NCT01224171].

Sustained Clinical Remission With Vedolizumab in Patients With Moderate-to-Severe Ulcerative Colitis

Abstract Background Sustaining clinical remission is an important treatment goal in moderate-to-severe UC. This post hoc exploratory analysis assessed the long-term efficacy of vedolizumab in the subset of patients with UC in the GEMINI 1 study who were in clinical remission by week 14 after 3 induction doses, administered at weeks 0, 2, and 6. Methods Sustained clinical remission (primary endpoint) was evaluated using 2 definitions: (1) a partial Mayo Score (pMS) of ≤2 with no subscore >1 and (2) a rectal bleeding subscore (RBS) of 0 throughout weeks 14, 26, 38, and 52. Results The proportion of patients in clinical remission at week 14 was significantly higher in patients receiving vedolizumab (n = 620) compared with placebo (n = 149) (pMS: 32.7% vs 20.1% [percentage-point difference (∆) 12.6%; 95% confidence interval [CI], 5.2–20.0]; RBS: 47.3% vs 28.9% [∆18.4%; 95% CI, 10.1–26.7]). Of patients in clinical remission at week 14, a significantly higher proportion of vedolizumab-treated patients achieved sustained clinical remission compared with placebo (pMS: 66.5% vs 26.7%; ∆39.8%; 95% CI, 22.7–56.9; RBS: 56.7% vs 20.9%; ∆35.7%; 95% CI, 22.3–49.1). Findings were consistent in tumor necrosis factor (TNF) antagonist-naive and antagonist-failure patients. Conclusion Compared with placebo, 35%–40% more patients receiving a full induction course of vedolizumab had sustained clinical remission after 52 weeks of therapy. This result was observed irrespective of TNF antagonist treatment history. Clinical remission at week 14 may therefore be a predictor for sustained clinical remission with vedolizumab.

DOP026 Sustained remission with vedolizumab in patients with moderately to severely active ulcerative colitis: a GEMINI 1 post hoc analysis of week 14 remitters

Background: Sustained remission is a key therapeutic goal in ulcerative colitis (UC). Vedolizumab (VDZ) was more effective than placebo as induction and maintenance therapy in patients (pts) with moderately to severely active UC in the GEMINI 1 study (NCT00783718). This post hoc analysis assessed su