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Cost analysis in a prospective European population-based inception cohort : is there a cost-saving effect of biological therapy?

Background The role of environmental factors in development of inflammatory bowel disease (IBD) remains uncertain. The aim of the present study was to assess a number of formerly suggested environmental factors in a case-control study of an unselected and recently diagnosed group of patients with IBD and a control group of orthopaedic patients. Methods A total of 123 patients diagnosed with Crohn's disease (CD) and 144 with ulcerative colitis (UC) in Copenhagen (2003–2004) were matched 1:1 on age and gender to 267 orthopaedic controls. Participants received a questionnaire with 87 questions concerning environmental factors prior to IBD/orthopaedic admission. Odds ratios (OR) were calculated by logistic regression. Results Being breastfed > 6 months (OR, 0.50; 95% CI, 0.23–1.11) and undergoing tonsillectomy (OR, 0.49; 95% CI, 0.31–0.78) decreased the odds for IBD, whereas appendectomy decreased the odds for UC only (OR, 0.29; 95% CI, 0.12–0.71). Vaccination against pertussis (OR, 2.08; 95% CI, 1.07–4.03) and polio (OR, 2.38; 95% CI, 1.04–5.43) increased the odds for IBD, whereas measles infection increased the odds for UC (OR, 3.50; 95% CI, 1.15–10.6). Low consumption of fibres and high consumption of sugar were significantly associated with development of CD and UC. Smoking increased the risk for CD and protected against UC. Conclusion Among Danish patients with CD and UC belonging to an unselected cohort, disease occurrence was found to be associated both with well-known factors such as smoking and appendectomy, and with more debated factors including breastfeeding, tonsillectomy, childhood vaccinations, childhood infections, and dietary intake of fibres and sugar.

Disease course during the first five years following diagnosis in a prospective European population-based inception cohort - the ECCO-EpiCom cohort

Change in Crohn's disease behavior in a prospective European population-based inception cohort - the ECCO-EpiCom cohort

Frequency of anaemia and anaemia subtypes in east-west European inception cohort : an ECCO-EpiCom cohort study

The risk of proximal disease extension in patients with limited ulcerative colitis in a prospective European population-based inception cohort - the ECCO-EpiCom cohort

The cost of investigations and medical treatment including biological therapy in a European inception cohort from the biological era : An ECCO-EpiCom study

in all study groups (105.8% vs 114.3% RDA in normal controls; 88.7% vs 109.2% RDA in diseased controls, 100.4% vs 87.6% RDA in IBD. Conclusions: In this study IBD patients had a significantly lower Ca intake than healthy controls. In accordance to previous studies, gender and age, more than diagnosis, are relevant factors in determining inadequate Ca intake. The trend is more marked in IBD, especially in postmenopausal women. Selfreported lactose intolerance, leading to dietary restrictions, is the single major determinant of low Ca intake in all pts groups, irrespective to diagnosis, age and gender. Inadequate Ca intake is observed in about one third of IBD pts and represents an easily reversible risk factor for osteoporosis. The observation that celiac patients on low gluten diet have a Ca intake well over RDA, further supports the need for tailored nutrition advice also in ulcerative colitis and Crohn’s disease.

Is there an east-west gradient in the incidence of IBD in Europe? : and further far east in China? First results from the epicom study

s of the 4th Congress of ECCO the European Crohn’s and Colitis Organisation S27 Conclusions: Faecal calprotectin and lactoferrin determination may be useful in predicting impending clinical relapse especially during the following 3 months in both CD and UC patients. P040 Reduced muscle mass and bone size in pediatric patients with inflammatory bowel disease S. Bechthold, M. Alberer, T. Arenz, S. Putzker, B. FilipiakPittroff, H.P. Schwarz, S. Koletzko*. Dr. von Haunersches Kinderspital, Munich, Germany Background and Aims: Decreased bone mineral density has been reported in children with inflammatory bowel disease (IBD). We used peripheral quantitative computed tomography (pQCT) to assess bone mineralization, geometry, and muscle cross sectional area (CSA) in pediatric IBD. Methods: In a cross sectional study, pQCT of the forearm was applied in 143 IBD patients (mean age 13.9±3.5 years), 29% were newly diagnosed, 98 had Crohn’s disease, and 45 ulcerative colitis. Auxological data, cumulative glucocorticoid dose, disease activity indices, laboratory markers for inflammation and bone metabolism were related to results of pQCT. Results: Patients were compromised in height ( 0.82±1.1 SD), weight ( 0.77±1.0 SD), muscle mass ( 1.12±1.0 SD), and total bone cross-sectional area ( 0.79±1.0 SD) compared to age and sex matched healthy controls (z-scores). In newly diagnosed patients, the ratio of bone mineral mass per muscle CSA was higher than in those with longer disease duration (1.00 versus 0.30, p = 0.007). Serum albumin level and disease activity correlated with muscle mass accounting for 41.0 % of variability in muscle mass (p < 0.01). Trabecular bone mineral density z-score was on average at the lower normal level ( 0.40±1.3 SD, p < 0.05). Conclusions: Reduced bone geometry was only in part explained by reduced height. The bone disease in children with IBD seems to be secondary to muscle wasting which is already present at diagnosis. With longer disease duration, bone adapts to the lower muscle CSA. Serum albumin concentration is a good marker for muscle wasting and abnormal bone development. Treatment options for Pediatric IBD patients should improve nutritional status and include physical activity programs to improve muscle mass, bone geometry and peak bone mass. P041 Faecal Calprotectin home test in ulcerative colitis is it possible? M. Elkjaer1 *, J. Burisch1, A. Roseth2, V. Voxen Hansen1, B. Deibjerg Kristensen1, D. Bremnes3, J. Slott Jensen4, P. Munkholm1. 1Herlev University Hospital, Copenhagen, Denmark, 2Aker University Hospital, Oslo, Norway, 3Skannex AS, Oslo, Norway, 4Slott Stat, Copenhagen, Denmark Background: Enzyme-linked immunosorbent assay (ELISA) is a quantitative method and the “Gold standard” for faecal Calprotectin (FC) analysis. A new quantitative method, the “Rapid Test” (RT), has been developed to be carried out by the lab technician. This test has further been developed into a “Home Test” (HT) to be carried out by the patients themselves. Aim: To compare the ELISA with the quantitative RT’s for FC measurement, read by a PC-scanner system or using an ordinary cell phone system. Methods: One drop of faecal extract was applied onto the RTdevice and the colour intensity of the test line was read after 10 min incubation time using a lap-top linked with an ordinary table top scanner. In the HT a picture of the same RT-device was taken using a cell phone with special software built in. The user takes a picture and a software package on the cell phone sends the picture to a server in Oslo by using Mobile Internet. In this study the RT and the HT was carried out by our lab technician. Results: One hundred seventy five faecal samples have been collected from ulcerative colitis (UC) patients involved in a randomised control trail “Constant-care”. The cut off level for normal FC is 50mg/kg. Comparison between the three tests was assessed with mean difference of 5.05mg/kg (95%CI; 16.52 26.61) in ELISA vs. RT. ELISA vs. HT mean difference of 26.73mg/kg (95%CI; 1.31 52.16) and RT vs. HT mean difference 21.71mg/kg (95%CI; 11.46 31.95) of FC was found. The coefficient of variation (CV %) of ELISA vs. HT was in median 2.81% (range, 0 21.60%) and 6.15% (range, 0 41.59%), p-value

s of the 4th Congress of ECCO the European Crohn’s and Colitis Organisation S97 of the disease. We therefore wanted to investigate whether granuloma formation should be seen as a stable trait in CD patients and also studied if this was influenced by a genetic predisposition. Materials and Methods: From a cohort of 466 CD patients who underwent a bowel resection in the period between 1 1 1991 and 31 12 2007 we identified 88 patients with two or more bowel resections in that time period (55.7% male, median [interquartile range, IQR] age at diagnosis 20.92 [17.05 28.51] years, median [IQR] age at first surgery 32.81 [22.93 41.64] years, median [IQR] time between surgeries 5.76 [3.8 8.96] years. Revision of pathology slides (average of 10 slides per resection specimen) was performed to classify patients as granuloma positive or negative at each surgery. Epithelioid granulomas were defined as a well circumscribed collection of at least five epithelioid macrophages (activated histiocytes with a homogenous eosinophilic cytoplasm) with or without multinucleated giant cells. All patients were furthermore genotyped for 56 selected SNPs in human homologues of yeast autophagy (Atg) genes, using the Sequenom MassARRAY® platform. Results: In 71.6% of patients (n = 63) no change in granuloma status was observed with subsequent surgeries. Among these patients, 58.7% were classified as granuloma positive and 41.3% as granuloma negative. We could not find significant differences in age at first surgery, disease duration to first surgery or time between surgeries between patients whose granuloma status changed and the patients in whom it remained unchanged. Genotype and allele frequencies for the studied polymorphisms did not differ between patients whose granuloma status did or did not change. Conclusions: Granuloma formation appears to be a stable trait in the majority of CD patients. This raises the hypothesis that an underlying intrinsic defect may make a patient prone to develop granulomas. Genetic variants in autophagy genes do not seem to play a role in this resepect. P219 Overall and organ-specific extra-intestinal cancer in inflammatory bowel disease: a meta-analysis of population-based studies N. Pedersen Jr.1 *, D. Duricova2, M. Elkjaer3. 1Herlev University Hospital, Taastrup, Denmark, 2Charles University, Prague, Czech Republic, 3Herlev University Hospital, Herlev, Denmark Aim: To describe the risk of overall and organ-specific extraintestinal cancer (EIC) in inflammatory bowel disease (IBD), Crohn’s disease (CD) and ulcerative colitis (UC) based on population-based cohort studies. Methods: The MEDLINE (January 1980 February 2008) and abstracts from international conferences (UEGW, DDW 2004 2007) were searched for related articles using defined search criteria. Additionally, reference lists of the articles were reviewed. Papers fulfilling the inclusion criteria were studied on population size, time of follow-up, type of cancer and observed to expected cancers. The overall pooled risk estimates (standardized incidence ratio (SIR), observed/expected) were calculated using STATA meta-analysis software. Results: Eight papers fulfilled the inclusion criteria and reported on extra-intestinal cancer in IBD (n = 5), CD (n = 6) and UC (n = 5). The pooled SIR for EIC was not increased in IBD overall (SIR, 1.1; 95%CI 0.97 1.27) or in CD (SIR 1.13, 95%CI 0.89 1.40) and UC (SIR 1.04, 95%CI 0.92 1.16) separately. However, patients with IBD had significantly increased risk of cancer of the liver-biliary system (SIR 1.94, 95%CI 1.07 3.54) and skin (squamous cell, SIR 1.79, 95%CI 1.01 3.16; melanoma, SIR 1.17, 95%CI 1.66 2.08). In separate analyses, CD patients had a significantly increased risk of cancer of the upper gastrointestinal tract (SIR 2.87, 95%CI 1.66 4.96), stomach (SIR 2.05, 95%CI 1.06 3.97), lung (SIR 1.82, 95%CI 1.18 2.81), urinary bladder (SIR 2.03, 95%CI 1.14 3.63) and skin (SIR 2.35, 95%CI 1.43 3.86), but a decreased risk of corpus uteri cancer (SIR 0.84, 95%CI 0.36 0.96). Patients with UC had a significantly increased risk of cancer of the liver-biliary system (SIR 2.58, 95%CI 1.58 4.22) and a decreased risk of lung cancer (SIR 0.39, 95%CI 0.20 0.74). Conclusions: IBD patients are not at increased overall risk of developing extra-intestinal cancer but the organ-specific pattern differs from that of the general population. CD patients are at increased risk of developing upper gastrointestinal cancer, lung, urinary bladder, and squamous cell carcinoma, and at decreased risk of corpus uteri cancer. UC patients have an increased risk of liver-biliary cancer counterweighted by a decreased risk of lung cancer. P220 The NOD2 variants rs2066843 and rs2076756 are novel independent Crohn’s disease susceptibility gene variants associated with severe penetrating disease phenotype resulting in frequent need for surgery J. Seiderer1 *, J. Glas1, J. Diegelmann1, G. Pasciuto1, C. Tillack1, S. Pfennig1, M. Jurgens1, A. Konrad1, H. Torok1, U. Schiemann2, T. Griga3, W. Klein4, J.T. Epplen4, T. Mussack5, P. Lohse1, B. Goke1, T. Ochsenkuhn1, M. Folwaczny5, B. Muller-Myhsok6, S. Brand1. 1University of Munich Klinikum Groshadern, Munich, Germany, 2Inselspital Bern, Bern, Switzerland, 3Knappschaftskrankenhaus, Dortmund, Germany, 4Ruhruniversitat, Bochum, Germany, 5Klinikum der Universitat Munchen, Munich, Germany, 6Max-Planck-Institut fur Psychiatrie, Munich, Germany Background and Aims: A number of studies indicates a strong association of the three common NOD2/CARD15 variants p.R702W, p.G908R, and p.Leu1007fsX1008 with Crohn’s disease (CD) while the role of other NOD2 variants has not been investigated in detail. We therefore aimed to test the association and phenotypic consequences of two recently identified NOD2 variants (SNPs rs2066843 and rs2076756) in a large German cohort of inflammatory bowel disease (IBD) patients. Methods: Genomic DNA from 2750 individuals (CD: n = 832; ulcerative colitis (UC): n = 451; controls: n = 1478) was analyzed for the NOD2 variants rs2066843, rs2076756, rs2066844, rs2066845 and rs2066847. Results: The SNPs rs2066843 and rs2076756 were significantly associated with CD (p 40 years [A3; p = 0.032 for rs2066843, p = 0.007 for rs2076756 vs. wild-type (WT)]. WT patients were more likely to have colonic disease (L2; p = 0.041 for rs2066843, p = 0.032 for rs2076756 vs. homozygous) with a trend of more ileocolonic involvement (L3) in homozygous patients (rs2066843: p = 0.066; rs2076756: p = 0.058 vs. WT). Moreover, both SNPs were significantly associated with the need for disease-related surgery in CD patients homozygous for these variants (rs2066843: p = 0.015; rs2076756: p = 0.003 vs. WT). Patients homozygous for rs2076756 had a more severe disease behaviour with less non-stricturing, non-penetrating disease (B1, p = 0.023 vs. WT) and more stricturing, penetrating disease (B3, p = 0.015 vs. WT). In addition, in these patients higher rates of fistulas were found (p = 0.015 vs. WT). Conclusion: Our study identified SNPs rs2066843 and rs2076756 as novel independent CD susceptibility variants associated with later disease onset and a severe penetrating disease phenotype resulting in frequent need for surgery. by gest on A ril 5, 2016 http://eccoxfordjournals.org/ D ow nladed from

s of the 4th Congress of ECCO the European Crohn’s and Colitis Organisation S9 were randomized to receive maintenance therapy with CZP 400mg sc q2w or q4w through Week 24. Clinical response was defined as 100-point decrease from baseline in CDAI and remission as a CDAI score of 150 points. Results: At week 6, 62.0% (334/539) of patients who received open-label induction therapy with CZP were in clinical response. Of these responders, 329 entered the double-blind maintenance trial and were thus included in the modified intent-to-treat population (CZP q2w, n = 161; CZP q4w, n = 168). Clinical response and remission rates at Week 26 are shown in the table. There was no significant difference between q2w or q4w CZP dosing regimens with respect to response (CDAI decrease of 100 or 70 points from baseline [P = 0.55 and P = 0.74, respectively] or remission rates [P = 0.81]). No new safety signals were observed. Week 26 CZP, % patients q2w (n = 161) q4w (n = 168) CDAI 100 point decrease 36.6 39.9 CDAI 70 point decrease 41.0 42.9 CDAI 150 points 30.4 29.2 Conclusions: Sixty-two percent of patients with moderateto-severe CD who had previously responded to IFX and lost response or developed hypersensitivity responded to open-label induction therapy with CZP. Among patients who responded to induction therapy with CZP, continuing therapy with CZP 400mg q4w is as effective as CZP 400mg q2w for maintenance of response and remission at Week 26. 14 Clinical course and cost of care in ulcerative colitis: Markov chain analysis of a European prospective population-based cohort S. Odes1 *, H. Vardi2, M. Friger2, P. Munkholm3, D. Esser4, M. Elkjaer3, H. Waters5, E. Langholz6. 1Gastroenterology Department, Soroka Medical Center and Ben Gurion University of the Negev, Beer Sheva, Israel, 2Epidemiology Department, Ben Gurion University of the Negev, Beer Sheva, Israel, 3Gastroenterology Department, Herlev Hospital and University of Copenhagen, Copenhagen, Denmark, 4Centocor BV, Leiden, Netherlands, 5Centocor Ortho Biotech Services, Malvern, PA, USA, 6Gastroenterology Department, Gentofte Hospital and University of Copenhagen, Copenhagen, Denmark Introduction: Predicting the clinical and economic outcome is difficult in ulcerative colitis, with its recurring-remitting course over many years, competing risk factors and multiple possible consequences. The Markov chain, a stochastic process with the Markov assumption, is an increasingly used approach in outcomes-analysis in complex disease. Methods: The European Collaborative Study of Inflammatory Bowel Disease (EC-IBD) Group incepted European and Israeli patients prospectively at diagnosis of ulcerative colitis from 1991 to 1993. Patients having more than 5 years unbroken tracking from diagnosis within a 10-year time horizon were grouped into clinical transition states by: (1) medical and surgical therapies recorded in continuous quarter-year cycles, (2) presence of flare-years in a minority ( 50%) of the follow-up years (hereafter called “minority flare-years” patients or “majority flare-years” patients respectively). Clinical course transition states (graded by treatment) were calculated by a Markov model (SPSS 16, STATA 10.1). The 5 transition states were defined as follows: “remission” (symptomatic treatment), “mild-moderate” (local corticosteroids, budesonide, mesalazine, antibiotics), “severe” (systemic steroids, immunosuppression, biologics), surgery (abdominal and pouch surgery), and death (from ulcerative colitis). Healthcare costs per patient per cycle were matched to the transition states. Results: 705 patients had 39208 cycles. In 644 cases with minority flare-years, the probability (expressed per cycle) of worsening (to a more severe state or surgery or death) of the “remission state” was 0.0811, of “mild-moderate state” 0.0763, of “severe state” 0.2664. In 61 cases with majority flare-years, the probability of worsening of the “remission state” was 0.2980, of “mild-moderate state” 0.1432, of “severe state” 0.2733. Minority flare-year patients in the initial “surgery state” had probabilities of 0.3291 for subsequent mild disease and 0.3924 for severe disease (pouchitis), and 0.0506 for pouch removal; majority flare-year patients had probabilities 0.3750 for mild or severe disease (pouchitis). The subsequent “surgery state” in the minority flare-years group acquired cases mostly from “surgery” (patients postcolectomy requiring pouch removal, probability 0.0506), and in the majority flare-years group from “severe” disease (patients requiring colectomy, probability 0.0104). Mean healthcare costs (euros/patient-cycle) were as follows: remission 93, mildmoderate 267, severe 939, surgery 8623, death 655. Surgery accounted for 72% of costs in year 1, and 83% in follow-up year 10. Conclusions: Severe ulcerative colitis has an inferior prognosis and high healthcare costs, with surgery accounting for the greatest expense. There is a considerable probability of pouchitis after surgery. Medical treatments must aim therefore to maintain patients in remission and avoid the need for surgical operations. 15 Laparoscopic-assisted versus open ileocolic resection for Crohn’s disease: long term results of a prospective randomized trial E.J. Eshuis1 *, J.F.M. Slors1, M.A. Cuesta2, R.E.G. Pierik3, P.C.F. Stokkers1, M.A.G. Sprangers1, W.A. Bemelman1. 1Academic Medical Center, Amsterdam, Netherlands, 2Free University Medical Center, Amsterdam, Netherlands, 3Isala Clinics, Zwolle, Netherlands Aim: Four meta-analyses exist evaluating the short term results of laparoscopic versus open ileocolic resection for Crohn’s disease. Little is known about the long term results of both procedures with respect to surgical recurrence rate, overall reoperation rate, incidence of incisional hernia, adhesive small bowel obstruction, quality of life (QOL) and Body Image (BI) and cosmesis. The objective of this study is to determine the long term results of a randomized multicenter study comparing laparoscopic with open ileocolic resection for Crohn’s disease. Materials and Methods: Sixty patients who participated in this trial were prospectively followed in the outpatient clinic. Patients had an ileocolic resection between 1999 and 2003. Primary outcome parameters were overall reoperation and readmission rate and re-resection rate for recurrent Crohn’s disease. Secondary outcomes were QOL, BI and cosmesis. Results: Five patients, 1 from the laparoscopic group and 4 from the open group were lost to follow up. The groups were comparable for characteristics as sex, age, and maintenance therapy. Mean follow-up was 6.8 years. Overall, 16/29 (55%) and 16/26 (62%) patients remained relapse-free after the ileocolic resection in the laparoscopic and open group respectively (p =NS). Resection of recurrent Crohn’s disease occurred in 2/29 (7%) and 3/26 (12%) patients ( p =NS). Two reoperations for incisional hernia were done in the open group (2/26 [8%]) vs. nil in the laparoscopic group. Reoperation for adhesive small bowel obstruction was done twice in the open group (2/26 [8%]) vs. nil in the laparoscopic group. Overall reoperation rate was 2/29 (7%) versus 7/26 (27%) by gest on Sptem er 4, 2016 http://eccoxfordjournals.org/ D ow nladed from

Background: In the Danish Crohn Colitis Database during the treatment era of 5-Aminosalicylic acid (5-ASA), steroids and surgery, it has been revealed that 8 years from diagnosis 44% of Crohn’s disease (CD) patients were characterized with a mild disease course, 20% with an aggressive (relapse every year) and 36% with a moderate disease course (relapse every other year). Aim: The outcome of the first treatment course with 5-ASA monotherapy (1.5 4.8 g/day) was retrospectively studied in a consecutive cohort of 345 patients with CD diagnosed 1952 2007. The immediate and long-term outcome of 5-ASA treament was described. Methods: A phenotyped model was used to assess treatment response: Immediate outcome (30 days after the start of 5-ASA) was defined as Complete response: Total regression of symptoms. Partial response: Improvement of symptoms. No response: No regression of symptoms with a need to shift from 5-ASA to an immunomodulator or surgery. Longterm outcome (irrespective of the length of the treatment) was defined as: Prolonged response: Still in complete/partial remission 1 year after induction of remission (either maintained on or after cessation of 5-ASA). 5-ASA dependency: Relapse on stable/reduced dose of 5-ASA requiring dose increase to regain remission or relapse within 1 year after 5-ASA cessation regaining complete/partial response after 5-ASA reintroduction. Results: One hundred sixty-five (48%) out of 345 patients had monotherapy with 5ASA. In 50% of them 5-ASA was initiated within one year of diagnosis with a range 0 49 years. Complete or partial response was obtained in 75% and no response in 25% of patients within 30 days of treatment. Among initial responders (complete/partial response), prolonged 5-ASA response was obtained in 47% (59) of patients, 5-ASA dependency in 31% (38) and 18% (22) of patients lost initial response to 5-ASA and had to shift to surgery (73%) or immunomodulator (27%). Five patients (4%) were not assessed in long-term outcome due to short treatment couse. Female gender was associated with higher probability to develop prolonged response or 5-ASA dependency (OR 2.68, 95%CI: 1.06 6.77, p = 0.03). The median duration (range) of 5-ASA course was 34 months (1 304) in prolonged responders, 63 (6 336) in 5-ASA dependent and 5 (2 10) in non-responders. Conclusion: Patients with CD may profit from 5-ASA treatment. Seventy-eight percent of initial responders obtained long-term benefit with 31% becoming 5-ASA dependent, resulting in 5 up to 28 years of remission on 5-ASA in 50% of them. Prospective studies are warranted to assess the role of 5-ASA in CD.