Adherence to Objective Therapeutic Monitoring and Outcomes in Patients with Inflammatory Bowel Disease with Adalimumab Treatment. A Real-world Prospective Study.

BACKGROUND AND AIMS: Objective monitoring and effective early treatment using a treat-to-target approach are key to improving therapeutic outcomes in IBD patients. This study aimed to assess adherence to objective monitoring (clinical, biomarkers, and endoscopy) and its impact on clinical outcomes. METHODS: A prospective, multicenter study included consecutive IBD patients starting on adalimumab therapy between January 2019 and December 2020. Disease activity, assessed by the Harvey-Bradshaw index (HBI), partial Mayo, C-reactive protein (CRP), fecal calprotectin (FCAL), and endoscopy were evaluated at adalimumab initiation and 3, 6, 9 and 12 months. Therapeutic drug monitoring, changes in treatment, drug sustainability, and clinical outcomes were assessed. RESULTS: 104 IBD patients were enrolled (78.8% CD, median age 34.3 years, disease duration 9 years). During the 12 months follow-up, high adherence to clinical activity assessment was observed in both CD (81.3%- 87.7%) and UC patients (76.5-90.9%). CRP measurement decreased over time in both CD (37.3%-54.9%) and UC (29.4%-50.0%). The adherence to serial FCAL monitoring was low in CD (22.7-31.3%) and UC patients (17.6-56.0%). UC patients had higher adherence to early endoscopic assessment (<6 months) compared to CD patients (40.9% vs. 21.5%). Adherence to early combined clinical and biomarkers resulted in earlier dose optimization in CD and UC (log-rank<0.001), but drug sustainability was not different. The patients with early combined adherence had a significantly higher clinical remission rate at 1 year compared to non-adherence (70.2% vs. 29.8%, p=0.007) but no significant difference in UC patients. CONCLUSIONS: The adherence to early objective monitoring with combined clinical and biomarkers assessment in IBD patients starting adalimumab therapy led to dose optimization and improved 1-year clinical remission in CD but did not change drug sustainability and clinical remission in UC.

Safety of Biological Therapies in Elderly Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis.

Background and Aim: Newer biologics appeared safer in landmark clinical trials, but their safety is understudied in vulnerable populations. The aim of the present study was to perform a systematic review and meta-analysis to assess the safety of available biologicals in the elderly IBD population. Methods: We systematically searched PubMed/Medline and conference proceedings between 1 April 1969 and 1 June 2021 to identify eligible studies that examined the safety of biologics in elderly patients with IBD. Of the 2885 articles and 12 congress abstracts identified, 12 peer reviewed papers and 3 abstracts were included after independent evaluation by two reviewers. The identified studies collected safety data on anti-TNF, vedolizumab (VDZ) and ustekinumab (UST). Results: Rates of AE and infections were not different among the biologics (AE mean rate: 11.3 (CI 95% 9.9-12.7)/100 pts-years; p = 0.11, infection mean rate: 9.5 (CI 95% 8.4-10.6)/100 pts-years; p = 0.56) in elderly IBD patients on anti-TNF, VDZ or UST. Infusion/injection reaction rates were more common on anti-TNFs (mean rate: 2.51 (CI 95% 1.7-3.4/100 pts-years; p = 0.02). and malignancy rates were higher on VDZ/UST (mean rate: 2.14 (CI 95% 1.6-2.8)/100 pts-years; p = 0.01). Conclusions: Rates of AEs and infections were not different among biologicals. Infusion/injection reactions were more common on anti-TNFs. Current data are insufficient to suggest the sequencing of biologicals in elderly patients based on safety.

Serological biomarkers for management of primary sclerosing cholangitis.

Clinical manifestations and progression of primary sclerosing cholangitis (PSC) are heterogeneous, and its pathogenesis is poorly understood. The importance of gut-liver interactions in the pathogenesis has been clinically confirmed and highlighted in different theories. Recent advances regarding biomarkers of biliary-gut crosstalk may help to identify clinically relevant PSC subgroups assisting everyday clinical work-up (e.g., diagnosis, disease stratification, or surveillance) and the exploration of potential therapeutic targets. Alkaline phosphatase produced by the biliary epithelium is consistently associated with prognosis. However, its level shows natural fluctuation limiting its use in individual patients. Inflammatory, cell activation, and tissue remodeling markers have been reported to predict clinical outcome. Elevated immunoglobulin (Ig) G4 level is associated with a shorter transplantation-free survival. IgG type atypical perinuclear anti-neutrophil cytoplasmic antibodies (P-ANCAs) are non-specific markers of various autoimmune liver diseases and may reflect an abnormal B-cell response to gut microbial antigens. IgG type atypical P-ANCA identifies PSC patients with particular clinical and genetic (for human leukocyte antigens) characteristics. The presence of IgA type anti-F-actin antibody (AAA) may predict a progressive disease course, and it is associated with enhanced mucosal immune response to various microbial antigens and enterocyte damage. IgA type anti-glycoprotein 2 (GP2) antibodies identify patients with a severe disease phenotype and poor survival due to enhanced fibrogenesis or development of cholangiocarcinoma. Elevated soluble vascular adhesion protein-1 (sVAP-1) level is associated with adverse disease outcomes in PSC. High sVAP-1 levels correlate with mucosal addressin cell adhesion molecule-1 (MAdCAM-1) expression in the liver that contributes to gut activated T-cell homing to the hepatobiliary tract. In the present paper, we review the evidence on these possible serological markers that could potentially help address the unmet clinical needs in PSC.

The Optimal Management of Fistulizing Crohn's Disease: Evidence beyond Randomized Clinical Trials.

Fistulizing Crohn's disease (FCD) remains the most challenging aspect of treating patients with CD. FCD can occur in up to 30% of patients with CD and may lead to significant disability and impaired quality of life. The optimal treatment strategies for FCD require a multidisciplinary approach, including a combined medical and surgical approach. The therapeutic options for FCD are limited due to sparse evidence from randomized clinical trials (RCTs). The current recommendations are mainly based on post hoc analysis from RCTs, real-world clinical studies and expert opinion. There is variation in everyday clinical practice amongst gastroenterologists and surgeons. The evidence for anti-tumor necrosis factor therapy is the strongest in the treatment of FCD. However, long-term fistula healing can be achieved in only 30-50% of patients. In recent years, emerging data in the advent of therapeutic modalities, including the use of new biologic agents, therapeutic drug monitoring, novel surgical methods and mesenchymal stem cell therapy, have been shown to improve outcomes in achieving fistula healing. This review summarizes the existing literature on current and emerging therapies to provide guidance beyond RCTs in managing FCD.

The Burden of Anemia Remains Significant over Time in Patients with Inflammatory Bowel Diseases at a Tertiary Referral Center.

BACKGROUND AND AIMS: Anemia is a common complication of inflammatory bowel diseases (IBD), as well as a predictor of poor outcomes. The aim of this study was to determine the prevalence of anemia over time and the management of moderate to severe anemia at a tertiary referral IBD center. METHODS: We retrospectively reviewed the occurrence of anemia at the time of referral or diagnosis and during follow-up at the McGill University Health Centre IBD center. Consecutive patients presenting with an outpatient visit between July and December 2016 and between December 2018 and March 2019 were included. Disease characteristics, biochemistry and medical management, including the need for intravenous iron therapy were recorded. RESULTS: 1,356 Crohn's disease (CD) and 1,293 ulcerative colitis (UC) patients [disease duration: 12 (IQR: 6-22) and 10 (IQR: 5-19) years respectively] were included. The prevalence of moderate to severe anemia at referral/diagnosis (15.4% and 8.5%) and during follow-up (11.1% and 8.1%) were higher in CD than in UC patients. In CD, previous resective surgery, perianal disease and elevated C-reactive protein (CRP) at assessment, while in UC steroid therapy, an elevated CRP and fecal calprotectin at assessment were associated with anemia in a multivariate analysis. Anemia improved by >2g/dL in 56.5% after 4-6 weeks (intravenous iron dose >1000 mg in 87% of patients). CONCLUSION: Anemia occurred frequently in this IBD cohort, at referral to the center and during follow-up, and contributes to the burden of IBD in referral populations. Most patients were assessed for anemia regularly and with accurate anemia workup; however, the targeted management of moderate to severe anemia was suboptimal.

Benefits of implementing a rapid access clinic in a high-volume inflammatory bowel disease center: Access, resource utilization and outcomes.

BACKGROUND: Emergency situations in inflammatory bowel diseases (IBD) put significant burden on both the patient and the healthcare system. AIM: To prospectively measure Quality-of-Care indicators and resource utilization after the implementation of the new rapid access clinic service (RAC) at a tertiary IBD center. METHODS: Patient access, resource utilization and outcome parameters were collected from consecutive patients contacting the RAC between July 2017 and March 2019 in this observational study. For comparing resource utilization and healthcare costs, emergency department (ED) visits of IBD patients with no access to RAC services were evaluated between January 2018 and January 2019. Time to appointment, diagnostic methods, change in medical therapy, unplanned ED visits, hospitalizations and surgical admissions were calculated and compared. RESULTS: 488 patients (Crohn's disease: 68.4%/ulcerative colitis: 31.6%) contacted the RAC with a valid medical reason. Median time to visit with an IBD specialist following the index contact was 2 d. Patients had objective clinical and laboratory assessment (C-reactive protein and fecal calprotectin in 91% and 73%). Fast-track colonoscopy/sigmoidoscopy was performed in 24.6% of the patients, while computed tomography/magnetic resonance imaging in only 8.1%. Medical therapy was changed in 54.4%. ED visits within 30 d following the RAC visit occurred in 8.8% (unplanned ED visit rate: 5.9%). Diagnostic procedures and resource utilization at the ED (n = 135 patients) were substantially different compared to RAC users: Abdominal computed tomography was more frequent (65.7%, P < 0.001), coupled with multiple specialist consults, more frequent hospital admission (P < 0.001), higher steroid initiation (P < 0.001). Average medical cost estimates of diagnostic procedures and services per patient was $403 CAD vs $1885 CAD comparing all RAC and ED visits. CONCLUSION: Implementation of a RAC improved patient care by facilitating easier access to IBD specific medical care, optimized resource utilization and helped avoiding ED visits and subsequent hospitalizations.

[The role of fecal calprotectin in the diagnosis and treatment of gastrointestinal diseases]. / A székletkalprotektin meghatározásának szerepe a bélbetegségek diagnosztikájában és kezelésében.

The diagnostics of gastrointestinal diseases have evolved significantly in the past few decades. Besides endoscopy and conventional imaging modalities, there is a growing interest for rapid point-of-care laboratory tests to help discriminate between diseases with similar clinical symptoms and/or help the follow-up of chronic conditions, predicting relapses. The fecal calprotectin testing is a routine diagnostic tool in many countries. It is also more and more accessible in Hungary as well. We aim to present a short review on the role and performance of fecal calprotectin test in the diagnosis and follow-up of gastrointestinal diseases, especially inflammatory bowel diseases, gastrointestinal infections, irritable bowel syndrome and pediatric conditions. By presenting the different cut-off values, sensitivity and specificity rates representative for each disease, we hope to further aid clinicians in decision-making regarding these conditions. Orv Hetil. 2019; 160(9): 322-328.

Natural disease course of Crohn's disease during the first 5 years after diagnosis in a European population-based inception cohort: an Epi-IBD study.

OBJECTIVE: The Epi-IBD cohort is a prospective population-based inception cohort of unselected patients with inflammatory bowel disease from 29 European centres covering a background population of almost 10 million people. The aim of this study was to assess the 5-year outcome and disease course of patients with Crohn's disease (CD). DESIGN: Patients were followed up prospectively from the time of diagnosis, including collection of their clinical data, demographics, disease activity, medical therapy, surgery, cancers and deaths. Associations between outcomes and multiple covariates were analysed by Cox regression analysis. RESULTS: In total, 488 patients were included in the study. During follow-up, 107 (22%) patients received surgery, while 176 (36%) patients were hospitalised because of CD. A total of 49 (14%) patients diagnosed with non-stricturing, non-penetrating disease progressed to either stricturing and/or penetrating disease. These rates did not differ between patients from Western and Eastern Europe. However, significant geographic differences were noted regarding treatment: more patients in Western Europe received biological therapy (33%) and immunomodulators (66%) than did those in Eastern Europe (14% and 54%, respectively, P<0.01), while more Eastern European patients received 5-aminosalicylates (90% vs 56%, P<0.05). Treatment with immunomodulators reduced the risk of surgery (HR: 0.4, 95% CI 0.2 to 0.6) and hospitalisation (HR: 0.3, 95% CI 0.2 to 0.5). CONCLUSION: Despite patients being treated early and frequently with immunomodulators and biological therapy in Western Europe, 5-year outcomes including surgery and phenotype progression in this cohort were comparable across Western and Eastern Europe. Differences in treatment strategies between Western and Eastern European centres did not affect the disease course. Treatment with immunomodulators reduced the risk of surgery and hospitalisation.

Quality of care indicators in inflammatory bowel disease in a tertiary referral center with open access and objective assessment policies.

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.

Occurrence of Anaemia in the First Year of Inflammatory Bowel Disease in a European Population-based Inception Cohort-An ECCO-EpiCom Study.

BACKGROUND AND AIMS: Anaemia is an important complication of inflammatory bowel disease [IBD]. The aim of this study was to determine the prevalence of anaemia and the practice of anaemia screening during the first year following diagnosis, in a European prospective population-based inception cohort. METHODS: Newly diagnosed IBD patients were included and followed prospectively for 1 year in 29 European and one Australian centre. Clinical data including demographics, medical therapy, surgery and blood samples were collected. Anaemia was defined according to the World Health Organization criteria. RESULTS: A total of 1871 patients (Crohn's disease [CD]: 686, 88%; ulcerative colitis [UC]: 1,021, 87%; IBD unclassified [IBDU] 164. 81%) were included in the study. The prevalence of anaemia was higher in CD than in UC patients and, overall, 49% of CD and 39% of UC patients experienced at least one instance of anaemia during the first 12 months after diagnosis. UC patients with more extensive disease and those from Eastern European countries, and CD patients with penetrating disease or colonic disease location, had higher risks of anaemia. CD and UC patients in need of none or only mild anti-inflammatory treatment had a lower risk of anaemia. In a significant proportion of patients, anaemia was not assessed until several months after diagnosis, and in almost half of all cases of anaemia a thorough work-up was not performed. CONCLUSIONS: Overall, 42% of patients had at least one instance of anaemia during the first year following diagnosis. Most patients were assessed for anaemia regularly; however, a full anaemia work-up was frequently neglected in this community setting.

3rd European Evidence-based Consensus on the Diagnosis and Management of Crohn's Disease 2016: Part 2: Surgical Management and Special Situations.

This paper is the second in a series of two publications relating to the European Crohn's and Colitis Organisation [ECCO] evidence-based consensus on the diagnosis and management of Crohn's disease [CD] and concerns the surgical management of CD as well as special situations including management of perianal CD and extraintestinal manifestations. Diagnostic approaches and medical management of CD of this ECCO Consensus are covered in the first paper [Gomollon et al JCC 2016].

[Indications, diagnoses and quality markers in upper and lower endoscopies in 2010 and 2011 at the 1st Department of Medicine, Semmelweis University, Budapest]. / A felso és alsó endoszkópiák indikációja, a diagnózisok megoszlása és minoségi mutatók 2010­2011-ben a Semmelweis Egyetem I. Belgyógyászati Klinikáján.

INTRODUCTION AND AIM: The aim was to assess the incidence of endoscopic findings based on the indication of the procedures in upper/lower endoscopies, and measuring quality indicators of colonoscopies at the 1st Department of Medicine, Semmelweis University, Budapest. METHOD: Data of 2987 patients (male/female:1361/1626, mean age: 60.7 years(y), SD: 16.7y) between 01.01.2010 and 31.12.2011 were analyzed. Both inpatient and outpatient records were collected. RESULTS: Incidence of peptic ulcer disease, esophageal varices, gastric polyps and gastric cancer were 10.8%, 4.5%, 6.1%, 2.9% in upper endoscopies, respectively. In colonoscopies colorectal polyps, diverticulosis, colorectal cancer and IBD were found in 29.9%, 22.4%, 6.9%, 9.7%, respectively. In patients having upper endoscopy with GI bleeding indication, older age (p<0.001), male gender (p<0.001, OR: 1.64), acenocoumarol/heparin use (p<0,001, peptic ulcers and esophageal varices were more frequent (p<0.001, OR: 2.83 and p<0.001, OR: 2.79), while in colonoscopies colorectal cancer had higher incidence (p<0.001, OR:3.27). 81% of colonoscopies were complete. Causes of incomplete procedures were ineffective bowel preparation (38.2%), technical difficulties (25.1%) and strictures (20.5%). CONCLUSION: The endoscopic findings and quality indicators (adenoma detection rate, coecal intubation rate) were in line with that reported in published series. Orv. Hetil., 2016, 157(52), 2074-2081.

Biosimilars in Inflammatory Bowel Disease: Facts and Fears of Extrapolation.

Biologic drugs such as infliximab and other anti-tumor necrosis factor monoclonal antibodies have transformed the treatment of immune-mediated inflammatory conditions such as Crohn's disease and ulcerative colitis (collectively known as inflammatory bowel disease [IBD]). However, the complex manufacturing processes involved in producing these drugs mean their use in clinical practice is expensive. Recent or impending expiration of patents for several biologics has led to development of biosimilar versions of these drugs, with the aim of providing substantial cost savings and increased accessibility to treatment. Biosimilars undergo an expedited regulatory process. This involves proving structural, functional, and biological biosimilarity to the reference product (RP). It is also expected that clinical equivalency/comparability will be demonstrated in a clinical trial in one (or more) sensitive population. Once these requirements are fulfilled, extrapolation of biosimilar approval to other indications for which the RP is approved is permitted without the need for further clinical trials, as long as this is scientifically justifiable. However, such justification requires that the mechanism(s) of action of the RP in question should be similar across indications and also comparable between the RP and the biosimilar in the clinically tested population(s). Likewise, the pharmacokinetics, immunogenicity, and safety of the RP should be similar across indications and comparable between the RP and biosimilar in the clinically tested population(s). To date, most anti-tumor necrosis factor biosimilars have been tested in trials recruiting patients with rheumatoid arthritis. Concerns have been raised regarding extrapolation of clinical data obtained in rheumatologic populations to IBD indications. In this review, we discuss the issues surrounding indication extrapolation, with a focus on extrapolation to IBD.

Association of extraintestinal manifestations and anaemia with disease outcomes in patients with inflammatory bowel disease.

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.

Optimizing biological therapy in Crohn's disease.

Anti-TNF therapy has revolutionized the treatment of inflammatory bowel diseases, including both Crohn's disease and ulcerative colitis. However, a significant proportion of patients does not respond to anti-TNF agents or lose response over time. Recently, therapeutic drug monitoring has gained a major role in identifying the mechanism and management of loss of response. The aim of this review article is to summarize the predictors of efficacy and outcomes, the different mechanisms of anti-TNF/biological failure in Crohn's disease and identify strategies to optimize biological treatment.

Tuberculin Skin Test and Quantiferon in BCG Vaccinated, Immunosuppressed Patients with Moderate-to-Severe Inflammatory Bowel Disease.

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.

Seasonal variability of vitamin D and bone metabolism in infliximab-treated paediatric Crohn's disease.

BACKGROUND: Paediatric Crohn's disease patients suffer from several complications, including low bone mineral density and inadequate serum levels of 25-hydroxy vitamin D. AIMS: The aim of this prospective study was to address the effect of infliximab therapy on bone metabolism, bone mineral density and vitamin D homeostasis. The seasonal variability of serum vitamin D levels in relation to infliximab treatment was also analysed. METHODS: Serum osteocalcin and beta-crosslaps (markers of bone metabolism), seasonal variability of vitamin D, and bone mineral density were assessed and followed throughout the yearlong treatment regimen of infliximab in 50 consecutive paediatric patients with moderate to severe Crohn's disease. RESULTS: Bone forming osteocalcin levels were significantly (p<0.001) increased during infliximab therapy. In contrast, no significant changes in beta-crosslaps and vitamin D levels were observed. Vitamin D levels were significantly different when the summer and winter periods were compared at week 0 (p=0.039); however, this difference was not detected after one year of infliximab therapy. Despite the beneficial clinical effect of infliximab, there was no significant change in bone mineral density Z-scores after one year of treatment. CONCLUSION: Infliximab may beneficially affect bone homeostasis. Moreover, seasonal variability in vitamin D levels observed prior to initiation of infliximab treatment was diminished after one year of treatment.

Rediscovery of the Anti-Pancreatic Antibodies and Evaluation of their Prognostic Value in a Prospective Clinical Cohort of Crohn's Patients: The Importance of Specific Target Antigens [GP2 and CUZD1].

BACKGROUNDS: Glycoprotein 2[GP2] and CUB zona pellucida-like domain 1[CUZD1] belong to protein families involved in gut innate immunity processes and have recently been identified as specific targets of anti-pancreatic autoantibodies [PAbs] in Crohn's disease[CD]. We aimed to determine the prognostic potential of novel target-specific PAbs regarding long-term disease course of an adult CD patient cohort. METHODS: Sera of 458 consecutive well-characterised IBD patients from a single referral IBD centre were tested by enzyme-linked immunosorbent assay [ELISA] with isoform 4 of recombinant GP2 [anti-MZGP2 and anti-GP2 IgA/IgG] and indirect immunofluorescence test [IIFT] system with GP2 and CUZD1 expressing transfected HEK 293 cells [anti-rPAg2 and rPAg1 IgA/IgG]. Clinical data were available on complicated disease or surgical interventions as well as disease activity and medical treatment during the prospective follow-up [median, 108 months]. RESULTS: Totals of 12.4% and 20.8% of CD patients were positive for IgA/IgG type of anti-GP2 and anti-CUZD1, respectively, with a significant difference compared with UC [p < 0.01]. Antibody status was stable over time. Agreement among three different anti-GP2 assays was good. Positivity for PAbs, mainly IgA subtypes, predicted a faster progression towards complicated disease course. In Kaplan-Meier analysis, time to surgery or development of perianal disease was associated with anti-GP2 IgA [pLogRank < 0.01] or anti-CUZD1 IgA [pLogRank < 0.001] positivity, respectively. Anti-CUZD1 IgA remained an independent predictor in the multivariate Cox-regression model (hazard ratio [HR]: 3.43, 95% confidence interval [CI]: 1.68-7.02, p < 0.001). CONCLUSIONS: The present study has shown that specific PAbs [especially IgA subtype] predict complicated disease course including the development of perianal disease in CD.

Low incidence of venous thromboembolism in inflammatory bowel diseases: prevalence and predictors from a population-based inception cohort.

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.