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Background and Aims: Rapid optimization of treatment algorithms and disease outcomes requires an objective measurement of disease activity in patients with Crohn's disease (CD). Our aim was to evaluate the impact of rapid-access to magnetic resonance imaging (MRI) on treatment optimization, clinical decision-making and outcomes for CD patients in a specialized tertiary care for inflammatory bowel disease (IBD) patients., Methods: A cohort of 75 referral CD patients (median age: 34, IQR: 25-43 years) who had underwent 90 fast-track MR enterography (MRE) scans between January 2014 and June 2016 were retrospectively enrolled. The MRI results were compared to clinical activity scores and biomarkers (C-reactive protein). The immediate impact of fast-track MRI on clinical decision-making, including changes in medical therapy, the need of hospitalization and surgery were evaluated., Results: The location of CD was ileo-colonic in 61% of the patients with perianal fistulas in 56% and previous surgeries in 55%. The indication for fast-track MRI scans was active disease (clinical or biomarker activity) in 55.6%. The radiological activity (including mild radiological signs to severe lesions) was detected in 94% of cases. Significant/severe MRI activity was depicted in 68% of these patients. Correlation between MRI radiological activity and clinical disease activity or colonoscopy was moderate (kappa: 0.609 and 0.652). A change in therapeutic strategy was made in 94.1% of cases with severe MRI radiological activity vs. 50% of patients without severe MRI radiological activity (p=0.001). Significant/severe MRI activity was followed by higher surgery rates among patients with clinical disease activity (50% vs. 12.5%; p=0.013). MRI performed on patients with clinical and biomarker remission identified disease activity in a significantly smaller proportion., Conclusions: Fast-track MRI had a great impact on patient management in CD patients with clinical or biomarker activity, leading to better patient stratification and faster optimization of the therapy (medical or surgical), while MRI revealed previously undiagnosed disease activity only in a small proportion of patients in clinical remission.

Background: Accelerated treatment strategy, including tight disease control and early aggressive therapy with immunosuppressives (IS) and biological agents have become increasingly common in inflammatory bowel disease (IBD). The aim of the present study was to estimate the early treatment strategy and outcomes in newly diagnosed patients with Crohn's disease (CD) between 2004 and 2008 and 2009-2015 in the whole IBD population in Hungary based on the administrative database of the National Health Insurance Fund (OEP)., Methods: We used the administrative database of the OEP, the only nationwide state-owned health insurance provider in Hungary. Patients were identified through previously reported algorithms using the ICD-10 codes for CD in the out-, inpatient (medical, surgical) non-primary care records and drug prescription databases between 2004 and 2015. Patients were stratified according to the year of diagnosis and maximum treatment steps during the first 3 years after diagnosis., Results: A total of 6173 (male/female: 46.12%/53.87%) newly diagnosed CD patients with physician-diagnosed IBD were found in the period of 2004-2015. The use of 5-ASA and steroids remained common in the biological era, while immunosuppressives and biologicals were started earlier and became more frequent among patients diagnosed after 2009. The probability of biological therapy was 2.9%/6.4% and 8.4%/13.7% after 1 and 3 years in patients diagnosed in 2004-2008/2009-2015. The probability of hospitalization in the first 3 years after diagnosis was different before and after 2009, according to the maximal treatment step (overall 55.7%vs. 47.4% (p = 0.001), anti-TNF: 73%vs. 66.7% (p = 0.103), IS: 64.6% vs. 56.1% (p = 0.001), steroid: 44.2%vs. 36.8% (p < 0.007), 5-ASA: 32.6% vs. 26.7% p = 0.157)). In contrast, surgery rates were not significantly different in patients diagnosed before and after 2009 according to the maximum treatment step (overall 16.0%vs.15.3%(p = 0.672) anti-TNF 26.7%vs.27.2% (p = 0.993), IS: 24.1%vs22.2% (p = 0.565), steroid 8.1%vs.7.9% (p = 0.896), 5-ASA 10%vs. 11% (p = 0.816))., Conclusions: IS and biological exposure became more frequent, while hospitalization decreased and surgery remained low but constant during the observation period. Use of steroids and 5-ASA remained high after 2009. The association between the maximal treatment step and hospitalization/surgery rates suggests that maximal treatment step can be regarded as proxy severity marker in patients with IBD.

Background: In the management of inflammatory bowel diseases, there is considerable variation in quality of care., Aims: The aim of this study was to evaluate structural, access/process components and outcome quality indicators in our tertiary referral IBD center., Methods: In the first phase, structural/process components were assessed, followed by the second phase of formal evaluation of access and management on a set of consecutive IBD patients with and without active disease (248CD/125UC patients, median age 35/39 years)., Results: Structural/process components of our IBD center met the international recommendations. At or around the time of diagnosis usual procedures were full colonoscopy in all patients, with ileocolonoscopy/gastroscopy/CT/MRI in 81.8/45.5/66.1/49.6% of CD patients. A total of 86.7% of CD patients had any follow-up imaging evaluation or endoscopy. The median waiting time for non-emergency endoscopy/CT/MRI was 16/14/22 days. During the observational period patients with flares (CD/UC:50.6/54.6%) were seen by specialist at the IBD clinic within a median of 1day with same day laboratory assessment, abdominal US, CT scan/surgical consult and change in therapy if needed. Surgery and hospitalization rates were 20.1/1.4% and 17.3/3.2% of CD/UC patients., Conclusion: Our results highlight that structural components and processes applied in our center are in line with international recommendations, including an open clinic concept and fast track access to specialist consultation, endoscopy and imaging., (Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: It has been previously shown that biosimilar infliximab CT-P13 is effective and safe in inducing remission in inflammatory bowel diseases. We report here the 1-year outcomes from a prospective nationwide inflammatory bowel disease cohort., Methods: A prospective, nationwide, multicenter, observational cohort was designed to examine the efficacy and safety of CT-P13 in the induction and maintenance treatment of Crohn's disease (CD) and ulcerative colitis (UC). Demographic data were collected and a harmonized monitoring strategy was applied. Clinical remission, response, and biochemical response were evaluated at weeks 14, 30, and 54, respectively. Safety data were registered., Results: Three hundred fifty-three consecutive inflammatory bowel disease (209 CD and 144 UC) patients were included, of which 229 patients reached the week 54 endpoint at final evaluation. Age at disease onset: 24/28 years (median, interquartile range: 19-34/22-39) in patients with CD/UC. Forty-nine, 53, 48% and 86, 81 and 65% of patients with CD reached clinical remission and response by weeks 14, 30, and 54, respectively. Clinical remission and response rates were 56, 41, 43% and 74, 66, 50% in patients with UC. Clinical efficacy was influenced by previous anti-tumor necrosis factor (TNF) exposure in patients with a drug holiday beyond 1 year. The mean C-reactive protein level decreased significantly in both CD and UC by week 14 and was maintained throughout the 1-year follow-up (both UC/CD: P < 0.001). Thirty-one (8.8%) patients had infusion reactions and 32 (9%) patients had infections. Antidrug antibody positivity rates were significantly higher throughout patients with previous anti-TNF exposure; concomitant azathioprine prevented antidrug antibody formation in anti-TNF-naive patients with CD., Conclusions: Results from this prospective nationwide cohort confirm that CT-P13 is effective and safe in inducing and maintaining long-term remission in both CD and UC. Efficacy was influenced by previous anti-TNF exposure; no new safety signals were detected.

Background: Therapeutic drug monitoring (TDM) aid therapeutic decision making in patients with inflammatory bowel disease (IBD) who lose response to anti-TNF therapy. Our aim was to evaluate the frequency and predictive factors of loss of response (LOR) to adalimumab using TDM in IBD patients., Methods: One hundred twelve IBD patients (with 214 TDM measurements, CD/UC 84/28, male/female 50/62, mean age CD/UC: 36/35 years) were enrolled in this consecutive cohort from two referral centres in Hungary. Demographic data were comprehensively collected and harmonized monitoring strategy was applied. Previous and current therapy, laboratory data and clinical activity were recorded at the time of TDM. Patients were evaluated either at the time of suspected LOR or during follow-up. TDM measurements were determined by commercial ELISA (LISA TRACKER, Theradiag, France)., Results: Among 112 IBD patients, LOR/drug persistence was 25.9%/74.1%. The cumulative ADA positivity (>10 ng/mL) and low TL (<5.0 μg/mL) was 12.1% and 17.8% after 1 year and 17.3% and 29.5% after 2 years of adalimumab therapy. Dose intensification was needed in 29.5% of the patients. Female gender and ADA positivity were associated with LOR (female gender: p < 0.001, OR:7.8 CI 95%: 2.5-24.3, ADA positivity: p = 0.007 OR:3.6 CI 95%: 1.4-9.5)., Conclusions: ADA development, low TL and need for dose intensification were frequent during adalimumab therapy and support the selective use of TDM in IBD patients treated with adalimumab. ADA positivity and gender were predictors of LOR.

Background and Aims: Biosimilar infliximab CT-P13 received European Medicines Agency [EMA] approval in June 2013 for all indications of the originator product. In the present study, we aimed to evaluate the predictors of short- and medium-term clinical outcome in patients treated with the biosimilar infliximab at the participating inflammatory bowel disease [IBD] centres in Hungary., Methods: Demographic data were collected and a harmonised monitoring strategy was applied. Clinical and biochemical activities were evaluated at Weeks 14, 30, and 54. Trough level [TL] and anti-drug antibody [ADA] concentrations were measured by enzyme-linked immunosorbent assay [ELISA] [LT-005, Theradiag, France] at baseline at 14, 30 and 54 weeks and in two centres at Weeks 2 and 6., Results: A total of 291 consecutive IBD patients (184 Crohn's disease [CD] and 107 ulcerative colitis [UC]) were included. In UC, TLs at Week 2 predicted both clinical response and remission at Weeks 14 and 30 (clinical response/remission at Week 14: area under the curve [AUC] = 0.81, p < 0.001, cut-off: 11.5 μg/ml/AUC = 0.79, p < 0.001, cut-off: 15.3μg/ml; clinical response/remission at Week 30: AUC = 0.79, p = 0.002, cut-off: 11.5 μg/ml/AUC = 0.74, p = 0.006, cut-off: 14.5 μg/ml), whereas ADA positivity at Week 14 was inversely associated with clinical response at Week 30 [58.3% vs 84.8% ,p = 0.04]. Previous anti-tumour necrosis factor [TNF] exposure was inversely associated with short-term clinical remission [Week 2: 18.8% vs 47.8%, p = 0.03, at Week 6: 38.9% vs 69.7%, p = 0.013, at Week 14: 37.5% vs 2.5%, p = 0.06]. In CD, TLs at Week 2 predicted short-term [Week 14 response/remission, AUCTLweek2 = 0.715-0.721, p = 0.05/0.005] but not medium-term clinical efficacy. In addition, early ADA status by Week 14 [p = 0.04-0.05 for Weeks 14 and 30], early clinical response [p < 0.001 for Weeks 30/54] and normal C-reactive protein [CRP] at Week 14 [p = 0.005-0.0001] and previous anti-TNF exposure [p = 0.03-0.0001 for Weeks 14, 30, and 54] were associated with short-and medium-term clinical response and remission., Conclusions: In UC, early TLs were predictive for short- and medium-term clinical efficacy, whereas in CD, Week 2 TLs were associated only with short-term clinical outcomes., (Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com)

Background: Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases associated with a substantial healthcare utilization., Aim: Our aim was to estimate the national prevalence of inflammatory bowel disease (IBD), CD and UC and to describe current drug treatment practices in CD and UC., Methods: Patients and drug dispensing events were identified according to international classification codes for UC and CD in in-patient care, non-primary out-patient care and drug prescription databases (2011-2013) of the National Health Insurance Fund., Results: A total of 55,039 individuals (men: 44.6%) with physician-diagnosed IBD were alive in Hungary in 2013, corresponding to a prevalence of 0.55% (95% CI, 0.55-0.56). The prevalence of CD 0.20% (95% CI, 0.19-0.20), and UC was 0.34% (95% CI, 0.33-0.34). The prevalence both in men and women was the highest in the 20-39 year-olds in CD. Current use of immunosuppressives and biological therapy was highest in the pediatric CD population (44% and 15%) followed by adult CD (33% and 9%), while their use was lowest in elderly patients. Interestingly, current use of 5-ASA (5-aminosalicylates) was high in both UC and CD irrespective of the age group., Conclusions: The Hungarian IBD prevalence based on nationwide database of the National Health Insurance Fund was high. We identified significant differences in the drug prescription practices according to age-groups., (Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Objective: The association between extraintestinal manifestations (EIMs) and disease activity suggest a common pathogenetic link with inflammatory bowel disease (IBD). We report on the association of EIMs and anaemia with long-term disease outcomes, including treatment steps, hospitalization, and surgery in the prospective population-based IBD inception cohort from Veszprem province., Methods: Data of 678 incident IBD patients (Crohn's disease/ulcerative colitis(CD/UC): 331/347) diagnosed from 1st January 2000 to 31st December 2012 were analyzed (CD: m/f: 176/155, median age at diagnosis: 28, IQR: 21-40 years, disease duration: 6, IQR: 2-9 years; UC: m/f: 200/147, median age at diagnosis: 36, IQR: 26-50 years, duration: 7, IQR: 4-10 years)., Results: EIMs were present in 30% of the CD and 17.3% of the UC patients. In CD, female gender (p = 0.02) need for steroid (p  < 0.001) and azathioprine (AZA) (p = 0.02), while in UC, young age at onset (p = 0.03), extensive disease (p = 0.003), female gender (p = 0.07), need for steroids (p < 0.001) and AZA (p = 0.004) and need for IBD-related hospitalization (p = 0.01) were associated with the presence of EIMs. Anaemia was present in 56.7% of the CD and 30.2% of the UC patients. In both CD and UC anaemia was associated with age at onset (pCD = 0.001, pUC = 0.04), disease location/extent (pCD = 0.02, pUC < 0.001), steroid and AZA use (for both pCD,UC < 0.001), need for surgery/colectomy (pCD < 0.001, pUC = 0.002) and hospitalization (pCD = 0.004, pUC < 0.001) and in CD, it was associated with anti TNF therapy(p = 0.002)., Conclusions: The presence of EIMs was associated with disease phenotype in UC and with treatment strategy in both CD and UC. Additionally, anaemia was associated with hospitalization and surgery in both CD and UC, suggesting that EIMs and anaemia may be helpful in stratifying disease severity in IBD.

Background and Aims: There are few data available on the effect of immunomodulator/biological therapy on the accuracy of the tuberculin skin test (TST) and interferon-gamma release assay (IGRA) in BCG-vaccinated immunosuppressed patients with inflammatory bowel disease (IBD). Our aim was to define the accuracy, predictors and agreement of TST and IGRA in a BCG-vaccinated immunosuppressed referral IBD cohort., Methods: 166 consecutive moderate-to-severe IBD patients (122 Crohn's disease, CD and 44 ulcerative colitis, UC) were enrolled in a prospective study from three centers. Patients were treated with immunosuppressives and/or biologicals. IGRA and TST were performed on the same day. Both in- and outpatient records were collected and comprehensively reviewed., Results: TST positivity rate was 23.5%, 21.1%,14.5% and 13.9% when cut-off values of 5, 10, 15 and 20mm were used. IGRA positivity rate was 8.4% with indeterminate result in 0.6%. Chest X-ray was suggestive of latent tuberculosis in 2 patients. Correlation between TST and IGRA was moderate (kappa: 0.39-0.41, p<0.001). In addition, a cut-off of 14 and 17mm for TST was defined to identify IGRA positivity in a ROC analysis (AUC: 0.76, p=0.03). TST and/or IGRA positivity was not influenced by medical therapy or disease phenotype. Importantly, smoking was identified as a risk factor for TST but not IGRA positivity (OR: 2.70-5.02, p<0.01, for TSTcut-offs=5-20mm)., Conclusion: TST and IGRA tests are partly complimentary methods, and additional testing by TST (with a cut-off of >15mm) should be considered to identify patients at risk for latent TB. Accuracy is satisfactory in BCG-vaccinated, immunosuppressed IBD patients. Smoking is a risk factor for TST positivity.

Background: Early identification of patients with Crohn's disease (CD) at risk of subsequent complications is essential for adapting the treatment strategy. We aimed to develop a prediction model including clinical and serological markers for assessing the probability of developing advanced disease in a prospective referral CD cohort., Methods: Two hundred and seventy-one consecutive CD patients (42.4% males, median follow-up 108 months) were included and followed up prospectively. Anti-Saccharomyces cerevisiae antibodies (ASCA IgA/IgG) were determined by enzyme-linked immunosorbent assay. The final analysis was limited to patients with inflammatory disease behaviour at diagnosis. The final definition of advanced disease outcome was having intestinal resection or disease behaviour progression., Results: Antibody (ASCA IgA and/or IgG) status, disease location and need for early azathioprine were included in a 3-, 5- and 7-year prediction matrix. The probability of advanced disease after 5 years varied from 6.2 to 55% depending on the combination of predictors. Similar findings were obtained in Kaplan-Meier analysis; the combination of ASCA, location and early use of azathioprine was associated with the probability of developing advanced disease (p < 0.001, log rank test)., Conclusions: Our prediction models identified substantial differences in the probability of developing advanced disease in the early disease course of CD. Markers identified in this referral cohort were different from those previously published in a population-based cohort, suggesting that different prediction models should be used in the referral setting., (Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Aims: Limited data are available on the hospitalization rates in population-based studies. Since this is a very important outcome measure, the aim of this study was to analyze prospectively if early hospitalization is associated with the later disease course as well as to determine the prevalence and predictors of hospitalization and re-hospitalization in the population-based ulcerative colitis (UC) inception cohort in the Veszprem province database between 2000 and 2012., Methods: Data of 347 incident UC patients diagnosed between January 1, 2000 and December 31, 2010 were analyzed (M/F: 200/147, median age at diagnosis: 36, IQR: 26-50 years, follow-up duration: 7, IQR 4-10 years). Both in- and outpatient records were collected and comprehensively reviewed., Results: Probabilities of first UC-related hospitalization were 28.6%, 53.7% and 66.2% and of first re-hospitalization were 23.7%, 55.8% and 74.6% after 1-, 5- and 10- years of follow-up, respectively. Main UC-related causes for first hospitalization were diagnostic procedures (26.7%), disease activity (22.4%) or UC-related surgery (4.8%), but a significant percentage was unrelated to IBD (44.8%). In Kaplan-Meier and Cox-regression analysis disease extent at diagnosis (HR extensive: 1.79, p=0.02) or at last follow-up (HR: 1.56, p=0.001), need for steroids (HR: 1.98, p<0.001), azathioprine (HR: 1.55, p=0.038) and anti-TNF (HR: 2.28, p<0.001) were associated with the risk of UC-related hospitalization. Early hospitalization was not associated with a specific disease phenotype or outcome; however, 46.2% of all colectomies were performed in the year of diagnosis., Conclusion: Hospitalization and re-hospitalization rates were relatively high in this population-based UC cohort. Early hospitalization was not predictive for the later disease course.

Aim: To analyze the prevalence, length and predictors of hospitalization in the biological era in the population-based inception cohort from Veszprem province., Methods: Data of 331 incident Crohn's disease (CD) patients diagnosed between January 1, 2000 and December 31, 2010 were analyzed (median age at diagnosis: 28; IQR: 21-40 years). Both in- and outpatient records were collected and comprehensively reviewed., Results: Probabilities of first CD-related hospitalization and re-hospitalization were 32.3%, 45.5%, 53.7% and 13.6%, 23.9%, 29.8%, respectively after one, three and five years of follow-up in Kaplan-Meier analysis. First-year hospitalizations were related to diagnostic procedures (37%), surgery or disease activity (27% and 21%). Non-inflammatory disease behavior at diagnosis (HR = 1.32, P = 0.001) and perianal disease (HR = 1.47, P = 0.04) were associated with time to first CD-related hospitalization, while disease behavior change (HR = 2.38, P = 0.002) and need for steroids (HR = 3.14, P = 0.003) were associated with time to first re-hospitalization in multivariate analyses. Early CD-related hospitalization (within the year of diagnosis) was independently associated with need for immunosuppressives (OR = 2.08, P = 0.001) and need for surgeries (OR = 7.25, P < 0.001) during the disease course., Conclusion: Hospitalization and re-hospitalization rates are still high in this cohort, especially during the first-year after the diagnosis. Non-inflammatory disease behavior at diagnosis was identified as the pivotal predictive factor of both hospitalization and re-hospitalization.

Aim: To analyze the incidence and possible risk factors in hospitalized patients treated with Clostridium difficile infection (CDI)., Methods: A total of 11751 patients were admitted to our clinic between 1 January 2010 and 1 May 2013. Two hundred and forty-seven inpatients were prospectively diagnosed with CDI. For the risk analysis a 1:3 matching was used. Data of 732 patients matched for age, sex, and inpatient care period and unit were compared to those of the CDI population. Inpatient records were collected from an electronic hospital database and comprehensively reviewed., Results: Incidence of CDI was 21.0/1000 admissions (2.1% of all-cause hospitalizations and 4.45% of total inpatient days). The incidence of severe CDI was 12.6% (2.63/1000 of all-cause hospitalizations). Distribution of CDI cases was different according to the unit type, with highest incidence rates in hematology, gastroenterology and nephrology units (32.9, 25 and 24.6/1000 admissions, respectively) and lowest rates in 1.4% (33/2312) in endocrinology and general internal medicine (14.2 and 16.9/1000 admissions) units. Recurrence of CDI was 11.3% within 12 wk after discharge. Duration of hospital stay was longer in patients with CDI compared to controls (17.6 ± 10.8 d vs 12.4 ± 7.71 d). CDI accounted for 6.3% of all-inpatient deaths, and 30-d mortality rate was 21.9% (54/247 cases). Risk factors for CDI were antibiotic therapy [including third-generation cephalosporins or fluoroquinolones, odds ratio (OR) = 4.559; P < 0.001], use of proton pump inhibitors (OR = 2.082, P < 0.001), previous hospitalization within 12 mo (OR = 3.167, P < 0.001), previous CDI (OR = 15.32; P < 0.001), while presence of diabetes mellitus was associated with a decreased risk for CDI (OR = 0.484; P < 0.001). Treatment of recurrent cases was significantly different from primary infections with more frequent use of vancomycin alone or in combination (P < 0.001), and antibiotic therapy duration was longer (P < 0.02). Severity, mortality and outcome of primary infections and relapsing cases did not significantly differ., Conclusion: CDI was accounted for significant burden with longer hospitalization and adverse outcomes. Antibiotic, PPI therapy and previous hospitalization or CDI were risk factors for CDI.

Objective: Patients with inflammatory bowel diseases (IBD) are considered to have an increased risk for venous thromboembolism (VTE). The aim of the present study was to analyze the incidence and risk factors of VTE in a population-based inception cohort in the Veszprem province database between 1977 and 2012., Material and Methods: A total of 1708 incepted IBD patients were included (male/female: 879/829; CD (Crohn's disease): 648, age at onset: 29, interquartile range (IQR): 22-39; UC (ulcerative colitis): 1060, age at onset: 36, IQR: 26-50 years). Both in- and outpatient records were collected and comprehensively reviewed and followed up for a total of 21,369 patient-years., Results: Twenty-two VTE events were identified in 19 patients (6 events in 5 CD and 16 in 14 UC patients). The incidence rate of VTE in IBD was 1.03 per 1000 patient-years. The risk of VTE in UC was associated with extensive location (odds ratio (OR): 3.25, 95% confidence interval (CI): 1.13-9.35), presence of fulminant episode during the disease course (OR: 4.15, 95% CI: 1.28-13.5), smoking (OR: 3.46, 95% CI: 1.14-10.5), and need for steroids (OR: 2.97, 95% CI: 0.99-8.92)., Conclusion: The incidence of VTE was lower than previously reported. The incidence was higher in males and in UC it was associated with extensive disease, fulminant episodes, corticosteroids-requiring disease and smoking, but not with age at onset.

Background: Hospitalization is an important outcome measure and a major driver of costs in patients with inflammatory bowel disease. We analysed medical and surgical hospitalization rates and predictors of hospitalization before and during anti-TNF therapy., Methods: Data from 194 consecutive patients were analysed retrospectively (males, 45.4%, median age at diagnosis, 24.0 years, infliximab/adalimumab: 144/50) in whom anti-TNF therapy was started after January 1, 2008. Total follow-up was 1874 patient-years and 474 patient-years with anti-TNF exposure., Results: Hospitalization rates hospitalization decreased only in Crohn's disease (odds ratio: 0.59, 95% confidence interval: 0.51-0.70, median 2-years' anti-TNF exposure) with a same trend for surgical interventions (p=0.07), but not in ulcerative colitis. Need for hospitalization decreased in Crohn's disease with early (within 3-years from diagnosis, p=0.016 by McNemar test), but not late anti-TNF exposure. At logistic regression analysis complicated disease behaviour (p=0.03), concomitant azathioprine (p=0.02) use, but not anti-TNF type, gender, perianal disease or previous surgeries were associated with the risk of hospitalization during anti-TNF therapy., Conclusion: Hospitalization rate decreased significantly in patients with Crohn's disease but not ulcerative colitis after the introduction of anti-TNF therapy and was associated with time to therapy. Complicated disease phenotype and concomitant azathioprine use were additional factors defining the risk of hospitalization., (Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Limited data are available on paediatric inflammatory bowel diseases in Eastern Europe. Our aim was to analyse disease characteristics in the population-based Veszprem province database between 1977 and 2011., Methods: 187 (10.5%, ulcerative colitis/Crohn's disease/undetermined colitis: 88/95/4) out of 1565 incident patients were diagnosed with a paediatric onset in this population-based prospective inception cohort., Results: The incidence of Crohn's disease and ulcerative colitis increased from 0 and 0.7 in 1977-1981 to 7.2 and 5.2 in 2007-2011 per 100,000 person years. Ileocolonic location (45%) and inflammatory disease behaviour (61%) were most frequent in Crohn's disease, while azathioprine use was frequent (66%) and surgical resection rates were high (33% at 5 years) in cases with paediatric onset. In ulcerative colitis, 34% of patients were diagnosed with extensive disease, with high rates of disease extension (26% and 41% at 5 and 10 years), fulminant episodes (19.3%) and systemic steroid use (52.3%). The cumulative rate of colectomy was low (6.9%)., Conclusions: The incidence of paediatric inflammatory bowel diseases has rapidly increased in the last three decades in Western Hungary. Ileocolonic disease and a need for azathioprine were characteristic in paediatric Crohn's disease, while paediatric onset ulcerative colitis was characterised by extensive disease and disease extension, while the need for colectomy was low., (Copyright © 2013 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Crohn's disease (CD) is a multifactorial potentially debilitating disease. It has a variable disease course, but the majority of patients eventually develop penetrating or stricturing complications leading to repeated surgeries and disability. Studies on the natural history of CD provide invaluable data on its course and clinical predictors, and may help to identify patient subsets based on clinical phenotype. Most data are available from referral centers, however these outcomes may be different from those in population-based cohorts. New data suggest the possibility of a change in the natural history in Crohn's disease, with an increasing percentage of patients diagnosed with inflammatory disease behavior. Hospitalization rates remain high, while surgery rates seem to have decreased in the last decade. In addition, mortality rates still exceed that of the general population. The impact of changes in treatment strategy, including increased, earlier use of immunosuppressives, biological therapy, and patient monitoring on the natural history of the disease are still conflictive. In this review article, the authors summarize the available evidence on the natural history, current trends, and predictive factors for evaluating the disease course of CD.

Aim: To analyze the difference in disease course and need for surgery in patients with Crohn's disease (CD)., Methods: Data of 506 patients with incident CD were analyzed (age at diagnosis: 31.5 ± 13.8 years). Both hospital and outpatient records were collected prospectively with a complete clinical follow-up and comprehensively reviewed in the population-based Veszprem province database, which includes incident CD patients diagnosed between January 1, 1977 and December 31, 2008. Follow-up data were collected until December 31, 2009. All patients included had at least 1 year of follow-up available. Patients with indeterminate colitis at diagnosis were excluded from the analysis., Results: Overall, 73 patients (14.4%) required resective surgery within 1 year of diagnosis. Steroid exposure and need for biological therapy were lower in patients with early limited surgery (P < 0.001 and P = 0.09). In addition, surgery rates during follow-up in patients with and without early surgery differed significantly after matching on propensity scores (P < 0.001, HR = 0.23). The need for reoperation was also lower in patients with early limited resective surgery (P = 0.038, HR = 0.42) in a Kaplan-Meier and multivariate Cox regression (P = 0.04) analysis. However, this advantage was not observed after matching on propensity scores (P(Logrank) = 0.656, P(Breslow) = 0.498)., Conclusion: Long-term surgery rates and overall exposure to steroids and biological agents were lower in patients with early limited resective surgery, but reoperation rates did not differ.

Background & Aims: Since data is limited regarding the risk of colorectal cancer (CRC) in Crohn's disease (CD) patients who present with stenosing disease in the colon, this study was undertaken to assess CRC risk in such patients, using a population-based, Veszprem province database, which includes incidental patients diagnosed between January 1, 1977 and December 31, 2011., Methods: Data from 640 incidental CD patients were analyzed (M/F ratio: 321/319, age-at-diagnosis: 28 years (IQR: 22-38)). Both hospital and outpatient records were collected and comprehensively reviewed., Results: CRC was diagnosed in six CD patients during a follow-up of 7759 person-years. Sixty-two patients presented with colonic/ileocolonic disease and a stenotic lesion in the colon with a follow-up of 702 person-years (median: 10.5, IQR: 5-16years). Colorectal cancer developed in 6.5% (equalling 0.57/100 person-years), the SIR (6.53, 95% CI: 2.45-17.4) was increased with four patients observed versus 0.61 expected. In a Kaplan-Meier analysis, the probability of developing CRC was 5.5% and 7.5% after 5- and 10 years, respectively, versus 0.4% in patients with other phenotypes (HR: 18.8, p<0.001). A sensitivity analysis included patients with stenosing colonic lesion at diagnosis or during follow-up (n=91, follow-up: 1180 person-years, median: 12, IQR: 6-17years). The probability of developing CRC was 3.6% and 4.9% after 5- and 10 years, respectively., Conclusions: The risk of CRC in CD patients presenting with or developing a stenotic lesion in the colon is high even after a short disease duration, suggesting the need for careful surveillance.

Background and Aims: Prior studies suggest a small but significantly increased risk of lymphoma in adults with inflammatory bowel disease (IBD), especially in patients treated with thiopurines. No data was available from Eastern Europe. The aim of this study was to analyze the incidence of lymphomas as related to drug exposure, in a population-based Veszprem province database, which included incident cases diagnosed between January 1, 1977 and December 31, 2008., Methods: Data from 1420 incident patients were analyzed (UC: 914, age at diagnosis: 36.5 years; CD: 506, age at diagnosis: 28.5.5 years). Both in- and outpatient records were collected and comprehensively reviewed. The rate of lymphoma was calculated as patient-years of exposure per medication class, of medications utilized in IBD., Results: Of the 1420 patients, we identified three patients who developed lymphoma (one CLL, two low-grade B-cell NHL including one rectal case), during 19,293 patient-years of follow-up (median follow-up: 13 years). All three patients were male. None had received azathioprine or biologicals. The absolute incidence rate of lymphoma was 1.55 per 10,000 patient-years, with 3 cases observed vs. 2.18 expected, with a standardized incidence ratio (SIR) of 1.37 (95% confidence interval [CI]: 0.44-4.26). No cases have been exposed to either azathioprine or biologicals., Conclusions: The overall risk of lymphoma in IBD was not increased; only three cases were seen in this population-based incident cohort over a 30-year period. An association with thiopurine exposure was not found., (Copyright © 2012 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Background & Aims: Treatment of Crohn's disease (CD) by infliximab (IFX) has been associated with the induction of antinuclear (ANA) and anti-double strand DNA (dsDNA) autoantibodies and in some studies the formation of dsDNA antibodies was associated with lupus-like syndromes. The aims of this study were to analyse the relationship between the development of ANA and dsDNA antibodies during anti-tumor necrosis factor (TNF)α therapy and the clinical efficacy or adverse outcome in patients with inflammatory bowel disease (IBD)., Methods: Data of 96 CD patients (age at presentation: 25.1 years, folow-up: 5 years, males/females 43/53) treated with anti-TNFα for at least one-year were analyzed. Records of a total of 198 one-year treatment cycles were collected and levels of autoantibodies were determined at induction and after one-year treatment periods., Results: The majority of CD patients had ileocolonic (67.4%) and complicated disease (B2-B3: 72.6%) with perianal lesions (63.2%). At any time ANA or dsDNA positivity was 28.6% and 18%. Elevated level of ANA at induction or during anti-TNFα therapy was not associated with treatment efficacy or development of adverse outcomes. In contrast, treatment efficacy (dsDNA positivity no/partial response vs. remission: 68.5% vs. 31.5%, P=0.003) was inferior and adverse outcomes were more frequent in patients with dsDNA positivity during the anti-TNFα therapy in both univariate analysis and in logistic regression models (OR efficacy: 4.91, 95%CI: 1.15-20.8; OR adverse outcome: 3.81,95%CI 1.04-13.9)., Conclusions: Our data suggest that development of dsDNA during biological therapy may be associated with suboptimal treatment efficacy and adverse outcomes in CD patients.

Background: Previous studies suggest that smoking is an important environmental factor in inflammatory bowel diseases (IBDs), with dichotomous effects in ulcerative colitis (UC) and Crohn's disease (CD). The aim of this study was to analyze the relationship between smoking and IBD risk in a population-based database from Veszprem Province, which included incident cases diagnosed between January 1, 1977, and December 31, 2008., Methods: Data from 1420 incident patients were analyzed (UC: 914, age at diagnosis: 38.9 years; CD: 506, age at diagnosis: 31.5 years). Both inpatient and outpatient records were collected and comprehensively reviewed. Overall, smoking frequency in the adult general population was 36.1%., Results: Of patients with CD, 47.2% were current smokers at diagnosis. Smoking was more frequent in male patients (P = 0.002) and was associated with an increased risk of CD (odds ratio, 1.96; 95% confidence interval, 1.63-2.37; P < 0.001). In contrast, current smoking was protective against UC (odds ratio, 0.33; 95% confidence interval, 0.27-0.41). The effect of smoking was linked to gender (in CD, more deleterious in male patients) and age at diagnosis and was most prominent in young adults, with a difference already being seen in 18- to 19-year-olds. In CD, a change in disease behavior (P = 0.02), location from ileal or colonic to ileocolonic (P = 0.003), arthritis/arthropathy (P = 0.002), need for steroids (P = 0.06), or AZA (P = 0.038) was more common in current smokers. Smoking in UC was associated with more extensive disease (P = 0.01) and a tendency for decreased need for colectomy (P = 0.06)., Conclusions: Current smoking was associated with the risk of IBD. This effect was linked to gender and age at diagnosis and was most prominent in young adults. No association was observed in pediatric or elderly patients. The deleterious and protective effects of smoking on the course in CD and UC were partially confirmed.

Trends in current epidemiological data suggest that the incidence of inflammatory bowel diseases is changing. Eastern Europe previously was seen as a low incidence area; however, new data confirm that incidence and prevalence are quickly increasing in some countries, reaching moderate-to-high incidence as reported in Western European countries. The quality of the studies also improved. Recently, data became available on the natural history of the disease from Eastern European countries. Current trends are similar to those reported from Western Europe and North America, including less complicated disease at diagnosis, accelerated use of immunomodulators and decreased need for surgery in Crohn's disease, more cases of proctitis and relatively low colorectal cancer risk in ulcerative colitis. In addition, in-depth analysis of disease course enabled the identification of possible predictive factors leading to some novel findings, such as the association between the decline in surgery risk and early treatment strategy. In contrast, some unexplained differences exist, such as the low overall colectomy risk in ulcerative colitis., (Copyright © 2012 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Aim: To investigate the evolution of disease phenotype in adult and pediatric onset Crohn's disease (CD) populations, diagnosed between 1977 and 2008., Methods: Data of 506 incident CD patients were analyzed (age at diagnosis: 28.5 years, interquartile range: 22-38 years). Both in- and outpatient records were collected prospectively with a complete clinical follow-up and comprehensively reviewed in the population-based Veszprem province database, which included incident patients diagnosed between January 1, 1977 and December 31, 2008 in adult and pediatric onset CD populations. Disease phenotype according to the Montreal classification and long-term disease course was analysed according to the age at onset in time-dependent univariate and multivariate analysis., Results: Among this population-based cohort, seventy-four (12.8%) pediatric-onset CD patients were identified (diagnosed ≤ 17 years of age). There was no significant difference in the distribution of disease behavior between pediatric (B1: 62%, B2: 15%, B3: 23%) and adult-onset CD patients (B1: 56%, B2: 21%, B3: 23%) at diagnosis, or during follow-up. Overall, the probability of developing complicated disease behaviour was 49.7% and 61.3% in the pediatric and 55.1% and 62.4% in the adult onset patients after 5- and 10-years of follow-up. Similarly, time to change in disease behaviour from non stricturing, non penetrating (B1) to complicated, stricturing or penetrating (B2/B3) disease was not significantly different between pediatric and adult onset CD in a Kaplan-Meier analysis. Calendar year of diagnosis (P = 0.04), ileal location (P < 0.001), perianal disease (P < 0.001), smoking (P = 0.038) and need for steroids (P < 0.001) were associated with presence of, or progression to, complicated disease behavior at diagnosis and during follow-up. A change in disease location was observed in 8.9% of patients and it was associated with smoking status (P = 0.01), but not with age at diagnosis., Conclusion: Long-term evolution of disease behavior was not different in pediatric- and adult-onset CD patients in this population-based cohort but was associated to location, perianal disease and smoking status.

Background: C-reactive protein (CRP) is a traditional nonspecific marker of inflammation, with Crohn's disease (CD) being associated with a strong CRP response. Thus far, no clear cutoff values have been determined. The authors' aim was to investigate whether high-sensitivity (hs)-CRP is useful for the identification disease phenotype, active disease, and relapse during follow-up, using a classification based on the hs-CRP value at diagnosis., Methods: In all, 260 well-characterized, unrelated, consecutive CD patients (male/female: 120/140; duration: 7.0 ± 6.1 years), with a complete clinical follow-up, were included. Hs-CRP, clinical activity according to the Harvey-Bradshaw Index, and clinical data (disease phenotype according to the Montreal Classification, extraintestinal manifestations, smoking habits, medical therapy, and surgical events) were prospectively collected between January 1, 2008 and June 1, 2010. Medical records prior to the prospective follow-up period were analyzed retrospectively., Results: In all, 32.3% of CD patients had normal hs-CRP at diagnosis. Elevated hs-CRP at diagnosis was associated with disease location (P = 0.002), noninflammatory disease behavior (P = 0.058), and a subsequent need for later azathioprine/biological therapy (P < 0.001 and P = 0.024), respectively. The accuracy of hs-CRP for identifying patients with active disease during prospective follow-up was good (area under the curve [AUC]: 0.82, cutoff: 10.7 mg/L). AUC was better in patients with an elevated hs-CRP at diagnosis (AUC: 0.92, cutoff: 10.3 mg/L). In Kaplan-Meier and Cox-regression analyses, hs-CRP was an independent predictor of 3- (P = 0.007) or 12-month (P = 0.001) clinical relapses for patients in remission who had elevated hs-CRP at diagnosis. In addition, perianal involvement (P = 0.01) was associated with the 12-month relapse frequency., Conclusions: Our data suggest that hs-CRP positivity at diagnosis is associated with disease location and behavior, and in patients who are hs-CRP positive at diagnosis, is an accurate marker of disease activity and a predictor of short- and medium-term clinical flare-ups during follow-up., (Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.)

Objectives: Medical therapy for Crohn's disease (CD) has changed significantly over the past 20 years with increasing use of immunosuppressives. In contrast, surgery rates are still high and there is little evidence that disease outcomes for CD have changed over the past decades. The objective of this study was to analyze the evolution of the surgical rates and medical therapy in the population-based Veszprem province database., Methods: Data of 506 incident CD patients were analyzed (age at diagnosis: 31.5 years, s.d. 13.8 years). Both hospital and outpatient records were collected and comprehensively reviewed. The study population was divided into three groups by the year of diagnosis (cohort A: 1977-1989, cohort B: 1990-1998 and cohort C: 1999-2008)., Results: Overall, azathioprine (AZA), systemic steroid, and biological (only available after 1998) exposure was 45.8, 68.6, and 9.5%, respectively. The 1- and 5-year probability of AZA use were 3.2 and 6.2% in cohort A, 11.4 and 29.9% in cohort B, and 34.8 and 46.2% in cohort C. In a multivariate Cox-regression analysis, decade of diagnosis (P < 0.001, hazard ratio (HR)(cohorts B-C): 2.88-6.53), age at onset (P = 0.008, HR: 1.76), disease behavior at diagnosis (P < 0.001, HR(complicated): 1.76-2.07), and need for systemic steroids (P < 0.001, HR: 2.71) were significantly associated with the time to initiation of AZA therapy. Early AZA use was significantly associated with the time to intestinal surgery in CD patients; in a multivariate Cox analysis (HR: 0.43, 95% confidence interval (CI): 0.28-0.65) and after matching on propensity scores for AZA use (HR: 0.42, 95% CI: 0.26-0.67)., Conclusions: This population-based inception cohort has shown that the recent reduction in surgical rates was independently associated with increased and earlier AZA use.

Background: Adalimumab is a fully human monoclonal antibody targeting tumour necrosis factor with proven efficacy in the treatment of Crohn's disease (CD)., Aim: To investigate the predictors of medium-term clinical efficacy and mucosal healing during adalimumab therapy, in patients with CD, in specialised centres approved for biological therapy in Hungary., Methods: Data capture of the 201 CD patients was standardised and prospective (male/female: 112/89, median age: 33.0 years, duration: 8 years). Previous infliximab therapy had been administered in 48% of patients, concomitant steroids in 41%, azathioprine in 69% and combined therapy in 27% of patients., Results: Overall clinical response and remission rates at 24 weeks were 78% and 52%, respectively; at 52 weeks were 69% and 44%, respectively. Endoscopic improvement and healing were achieved in 43% and 24% of patients. In a logistic regression model, clinical efficacy and CRP at week 12, need for combined immunosuppression at induction, shorter disease duration and smoking were identified as independent predictors for 12-month clinical outcome, whereas CRP at week 12, clinical remission at week 24, inflammatory parameters and nonsmoking were associated to endoscopic improvement/healing. Intensification to weekly dosing was needed in 16% of patients. Parallel azathioprine therapy and clinical remission at week 12 were inversely associated with dose escalation., Conclusions: Clinical efficacy and normalised CRP at week 12 (early deep clinical remission) are associated with medium-term clinical efficacy and mucosal healing during adalimumab therapy, whereas need for combined immunosuppression at induction and smoking status are predictors for non-response. Parallel azathioprine therapy may decrease the probability for dose escalation., (© 2011 Blackwell Publishing Ltd.)