Javaria Mona Khalid

Epidemiology, severity, and treatment of chronic obstructive pulmonary disease in the United Kingdom by GOLD 2013

Objectives In 2013, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) updated the management strategy on COPD based on severity using a combined assessment of symptoms, degree of airflow limitation, and number of exacerbations. This study quantified prevalence and incidence of COPD in the United Kingdom and estimated disease severity by GOLD 2013 categories A/B (low risk) and C/D (high risk). Methods The Clinical Practice Research Datalink was used to identify COPD patients ≥40 years. Patient characteristics were described, and prevalence was calculated on December 31, 2013. Five-year incidence (2009–2013) was estimated, with rates standardized using 2011 UK population age and sex. To classify patients by GOLD categories, spirometry results, the modified British Medical Research Council grade, and history of exacerbations were used. Results The prevalent cohort comprised 49,286 patients with COPD with mean age 70 years; 51.0% were male. Overall prevalence was 33.3 per 1,000 persons (95% confidence interval [CI]: 33.1–33.6); 66.4% were classified as GOLD A/B and 33.6% as C/D. The standardized prevalence of GOLD A/B was 21.9 per 1,000 persons (95% CI: 21.7–22.1) and of C/D was 11.1 (95% CI: 10.9–11.2). A total of 27,224 newly diagnosed COPD patients were identified with mean age 67 years at diagnosis; 53.0% were male. Incidence was 2.2 per 1,000 person-years (95% CI: 2.2–2.3); 68.7% were classified in categories A/B and 31.3% in C/D, of which 17.2% did not receive COPD maintenance medication. Conclusion A third of COPD patients in the UK are considered high risk (GOLD 2013 categories C/D), and a third of patients are diagnosed for the first time at these severe stages. Given the progressive nature of the disease, results suggest that closer attention to respiratory symptoms for early detection, diagnosis, and appropriate treatment of COPD in the UK is warranted.

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

COPD exacerbations by disease severity in England

Objectives Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with accelerated disease progression and are important drivers of health care resource utilization. The study aimed to quantify the rates of COPD exacerbations in England and assess health care resource utilization by severity categories according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2013. Methods Data from the Clinical Practice Research Datalink linked to Hospital Episode Statistics were used to identify patients with a COPD diagnosis aged ≥40 years. Those with complete spirometric, modified Medical Research Council Dyspnea Scale information, and exacerbation history 12 months prior to January 1, 2011 (index date) were classified into GOLD severity groups. Study outcomes over follow-up (up to December 31, 2013) were exacerbation rates and resource utilization (general practitioner visits, hospital admissions). Results From the 44,201 patients in the study cohort, 83.5% were classified into severity levels GOLD A: 33.8%, GOLD B: 21.0%, GOLD C: 18.1%, and GOLD D: 27.0%. Mean age at diagnosis was 66 years and 52.0% were male. Annual exacerbation rates per person-year increased with severity, from 0.83 (95% confidence interval [CI]: 0.81–0.85) for GOLD A to 2.51 (95% CI: 2.47–2.55) for GOLD D. General practitioner visit rates per person-year also increased with severity, from 4.82 (95% CI: 4.74–4.93) for GOLD A to 7.44 (95% CI: 7.31–7.61) for GOLD D. COPD-related hospitalization rates per person-year increased from less symptoms (GOLD A: 0.28, GOLD C: 0.39) to more symptoms (GOLD B: 0.52, GOLD D: 0.84). Conclusion Patients in the most severe category (GOLD D) experienced nearly three times the number of exacerbations and COPD-related hospitalizations as those in the least severe category (GOLD A), in addition to increased general practitioner visits. Better patient management to stabilize the disease progression could allow for an improvement in exacerbation frequency and a reduction in health care resource utilization.

An evaluation of exact matching and propensity score methods as applied in a comparative effectiveness study of inhaled corticosteroids in asthma

Background Cohort matching and regression modeling are used in observational studies to control for confounding factors when estimating treatment effects. Our objective was to evaluate exact matching and propensity score methods by applying them in a 1-year pre–post historical database study to investigate asthma-related outcomes by treatment. Methods We drew on longitudinal medical record data in the PHARMO database for asthma patients prescribed the treatments to be compared (ciclesonide and fine-particle inhaled corticosteroid [ICS]). Propensity score methods that we evaluated were propensity score matching (PSM) using two different algorithms, the inverse probability of treatment weighting (IPTW), covariate adjustment using the propensity score, and propensity score stratification. We defined balance, using standardized differences, as differences of <10% between cohorts. Results Of 4064 eligible patients, 1382 (34%) were prescribed ciclesonide and 2682 (66%) fine-particle ICS. The IPTW and propensity score-based methods retained more patients (96%–100%) than exact matching (90%); exact matching selected less severe patients. Standardized differences were >10% for four variables in the exact-matched dataset and <10% for both PSM algorithms and the weighted pseudo-dataset used in the IPTW method. With all methods, ciclesonide was associated with better 1-year asthma-related outcomes, at one-third the prescribed dose, than fine-particle ICS; results varied slightly by method, but direction and statistical significance remained the same. Conclusion We found that each method has its particular strengths, and we recommend at least two methods be applied for each matched cohort study to evaluate the robustness of the findings. Balance diagnostics should be applied with all methods to check the balance of confounders between treatment cohorts. If exact matching is used, the calculation of a propensity score could be useful to identify variables that require balancing, thereby informing the choice of matching criteria together with clinical considerations.

Systematic review with meta-analysis: real-world effectiveness and safety of vedolizumab in patients with inflammatory bowel disease

BackgroundSelective patient recruitment can produce discrepancies between clinical trial results and real-world effectiveness.MethodsA systematic literature review and meta-analysis were conducted to assess vedolizumab real-world effectiveness and safety in patients with ulcerative colitis (UC) or Crohn’s disease (CD). MEDLINE, MEDLINE In-Process, EMBASE, and Cochrane databases were searched for real-world studies of vedolizumab in adult patients with UC/CD reporting clinical response, remission, corticosteroid-free remission, UC/CD-related surgery or hospitalization, mucosal healing, or safety published from May 1, 2014–June 22, 2017. Response and remission rates were combined in random-effects meta-analyses.ResultsAt treatment week 14, 32% of UC patients [95% confidence interval (CI) 27–39%] and 30% of CD patients (95% CI 25–34%) were in remission; and at month 12, 46% for UC (95% CI 37–56%) and 30% for CD (95% CI 20–42%). For UC, the rates of corticosteroid-free remission were 26% at week 14 (95% CI 20–34%) and 42% at month 12 (95% CI 31–53%); for CD they were 25% at week 14 (95%, CI 20–31%) and 31% at month 12 (95%, CI 20–45%). At month 12, 33–77% of UC and 6–63% of CD patients had mucosal healing. Nine percent of patients reported serious adverse events.ConclusionsVedolizumab demonstrated real-world effectiveness in patients with moderate-to-severely active UC or CD, with approximately one-half and one-third of patients, respectively, in remission at treatment month 12. These findings are consistent with clinical trial data and support the long-term benefit–risk profile of vedolizumab.

Rapid Response to Vedolizumab Therapy in Biologic-Naive Patients With Inflammatory Bowel Diseases

BACKGROUND & AIMS: Vedolizumab, a humanized monoclonal antibody against &agr;4&bgr;7 integrin, is used to treat adults with moderately to severely active ulcerative colitis (UC) and Crohns disease (CD). We investigated the time course of clinical response to vedolizumab in patients who were and were not previously treated with tumor necrosis factor (TNF) antagonists. METHODS: We performed a post‐hoc analysis of data from phase 3, randomized, controlled trials of vedolizumab vs placebo in adult patients with UC (N = 374) or CD (N = 784). We collected data on patient‐reported symptoms (rectal bleeding and stool frequency for patients with UC, abdominal pain and loose stool frequency for patients with CD) reported at weeks 2, 4, and 6 of treatment. We reported mean percentage score changes from baseline and proportions of patients who achieved predefined scores. We performed multivariate logistic regression analysis to identify factors associated with an early response (at week 2). RESULTS: In patients with UC (overall or naive to TNF antagonist therapy), a significantly greater percentage of patients given vedolizumab achieved the predefined composite symptom score at weeks 2, 4, and 6 compared to those given placebo. In patients with CD who were naive to TNF antagonists, a significantly greater percentage of patients given vedolizumab achieved the predefined score at weeks 2 and 4 compared to those given placebo. Among patients with UC given vedolizumab, 19.1% (overall) and 22.3% (TNF antagonist naive) achieved a composite score of rectal bleeding of 0 and stool frequency ≤1 at week 2 compared to 10% (overall) and 6.6% (TNF antagonist naive) of those receiving placebo. Among TNF antagonist‐naive patients with CD, 15.0% of those given vedolizumab achieved an average daily composite score of abdominal pain ≤1 and loose stool frequency ≤3 at week 2 (compared to 7.9% given placebo), and 23.8% of those given vedolizumab achieved these by week 4 (compared to 10.3% given placebo). CONCLUSIONS: In a post‐hoc analysis of data from phase 3 clinical trials, vedolizumab significantly improved patient‐reported symptoms of UC and CD as early as week 2 of treatment, continuing through the first 6 weeks—especially when given as first‐line biologic therapy. ClinicalTrials.gov no: NCT00783718, NCT00783692, NCT01224171.

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,

P470 Comparative effectiveness analysis of flares, hospitalisations, and corticosteroid use among biologic naïve patients with inflammatory bowel disease within 12 months of initiation of vedolizumab or infliximab

Background: This study aimed to compare IBD-related flare, hospitalisations, and corticosteroid use within one year of initiation of vedolizumab (VDZ) versus infliximab (IFX) among biologic-naive IBD patients in a real-world setting.Methods: We undertook retrospective analysis of data from 01/05/201

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

Asthma-Related Outcomes in Patients Initiating Extrafine Ciclesonide or Fine-Particle Inhaled Corticosteroids

Purpose Extrafine-particle inhaled corticosteroids (ICS) have greater small airway deposition than standard fine-particle ICS. We sought to compare asthma-related outcomes after patients initiated extrafine-particle ciclesonide or fine-particle ICS (fluticasone propionate or non-extrafine beclomethasone). Methods This historical, matched cohort study included patients aged 12-60 years prescribed their first ICS as ciclesonide or fine-particle ICS. The 2 cohorts were matched 1:1 for key demographic and clinical characteristics over the baseline year. Co-primary endpoints were 1-year severe exacerbation rates, risk-domain asthma control, and overall asthma control; secondary endpoints included therapy change. Results Each cohort included 1,244 patients (median age 45 years; 65% women). Patients in the ciclesonide cohort were comparable to those in the fine-particle ICS cohort apart from higher baseline prevalence of hospitalization, gastroesophageal reflux disease, and rhinitis. Median (interquartile range) prescribed doses of ciclesonide and fine-particle ICS were 160 (160-160) µg/day and 500 (250-500) µg/day, respectively (P<0.001). During the outcome year, patients prescribed ciclesonide experienced lower severe exacerbation rates (adjusted rate ratio [95% CI], 0.69 [0.53-0.89]), and higher odds of risk-domain asthma control (adjusted odds ratio [95% CI], 1.62 [1.27-2.06]) and of overall asthma control (2.08 [1.68-2.57]) than those prescribed fine-particle ICS. The odds of therapy change were 0.70 (0.59-0.83) with ciclesonide. Conclusions In this matched cohort analysis, we observed that initiation of ICS with ciclesonide was associated with better 1-year asthma outcomes and fewer changes to therapy, despite data suggesting more difficult-to-control asthma. The median prescribed dose of ciclesonide was one-third that of fine-particle ICS.