IBD-PODCAST Spain: A Close Look at Current Daily Clinical Practice in IBD Management.

BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) that contributes in part to irreversible bowel damage and long-term complications, reduced quality of life, invalidity, and economic burden. Suboptimal control of IBD is associated with higher healthcare resource utilization (HCRU), impaired quality of life (QoL), and reduced work productivity. AIMS: The IBD-PODCAST study aimed to assess the proportion of IBD patients with suboptimal control and its associated impact. METHODS: IBD-PODCAST is a cross-sectional, multicenter study that aimed to characterize the CD and UC population with optimal or suboptimal control according to the STRIDE-II criteria and patient- and physician-reported measures. Here we present the results of the Spanish cohort (n = 396). RESULTS: A total of 104/196 (53.1%) CD and 83/200 (41.5%) UC patients were found to have suboptimal disease control. Long-term treatment targets according to STRIDE-II were applied in 172 (87.8%) CD and 181 (90.5%) UC patients. 125 of 172 (72.7%) CD and 74 of 181 (40.9%) UC patients were currently treated with targeted immunomodulators. Patients with CD and UC and suboptimal disease control showed impaired QoL, higher HCRU and direct costs, and also loss of work productivity compared to those with optimal control. CONCLUSION: Despite a high rate of targeted immunomodulator therapy, a substantial proportion of IBD patients show suboptimal disease control according to the STRIDE II criteria. Those patients with suboptimal disease control exhibit impaired QoL, less work productivity, and higher HCRU, suggesting that there is considerable need for better treatment approaches in IBD.

[Current position on Vedolizumab for ulcerative colitis and Crohn's disease]. / Vedolizumab bei Colitis ulcerosa und Morbus Crohn: eine Standortbestimmung.

Vedolizumab, the first drug in the class of anti-integrin molecules, is newly approved for ulcerative colitis and Crohn's disease and can be prescribed in Germany since mid-2014. By a specific receptor binding a relatively gut-selective mode of action was achieved without the known side effects of the systemic immunosuppression of the anti-TNF-alpha antibodies. According to the present data the safety profile of Vedolizumab appears to be more favorable than that of the anti-TNF- alpha therapy. Vedolizumab is suitable for induction therapy in patients with ulcerative colitis and Crohn's disease, however the kinetic of response compared with the anti-TNF-alpha antibodies seems to be slower. For maintenance therapy the Vedolizumab data show a deep and sustained remission in patients initially responding to induction therapy with a lower loss of efficacy in the long-term treatment known from the anti-TNF-alpha therapy. On the basis of currently available data the efficacy of Vedolizumab in ulcerative colitis appears to be slightly better than in Crohn's disease.

[Rational and efficient diagnosis in different stages of Crohn's disease]. / Rationale und rationelle Diagnostik in unterschiedlichen Krankheitsphasen des Morbus Crohn.

The treatment of patients with inflammatory bowel disease has become more complex in recent years through the introduction of various immunosuppressive agents as well as the approval of monoclonal antibodies. Patients receiving such treatment must be carefully monitored. National and international guidelines define a diagnostic and therapeutic context for the practitioner, but can only partially respond to specific questions on the procedure for individual patients. Within the framework of a project initiated by Abbott entitled "IBD ahead" 34 German IBD experts have elaborated concrete proposals for the utility of clinical symptom assessment, endoscopy and the use of laboratory parameters including foecal markers of inflammation. Furthermore, we discuss the significance of conventional X-rays, computed tomography, ultrasound and magnetic resonance tomography. These recommendations are illustrated by case studies from everyday practice in the participating centres.

[IBD ahead 2010--Answering important questions in Crohn's disease treatment]. / IBD ahead 2010--Antworten auf zehn zentrale Fragen in der aktuellen Therapie des Morbus Crohn.

The treatment of patients with inflammatory bowel disease has become more complex in recent years through the introduction of various immunosuppressive agents as well as the approval of monoclonal antibodies against TNF-α and patients receiving such treatment must be carefully monitored. National and international guidelines define a diagnostic and therapeutic context for the practitioner, but can only partially respond to specific questions on the procedure for individual patients. Within the framework of a project initiated by Abbott entitled "IBD ahead" 38 German IBD experts have elaborated concrete proposals for dealing with corticosteroids, immunosuppressants and TNF-α antibodies on the basis of the published literature and their own personal experience in order to close the gap between these guidelines and daily clinical practice. Statements were developed on the choice of correct timing of initiation, dose and duration of the individual substances and on how to proceed with patients exhibiting treatment failure. Moreover, recommendations are also made on drug combination strategies, safety monitoring and the risks regarding the development of infectious complications and malignancies. These recommendations are illustrated by case studies from everyday practice in participating centres.

Inflammation, but Not the Underlying Disease or Its Location, Predicts Oral Iron Absorption Capacity in Patients With Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Anaemia is common in patients with inflammatory bowel disease [IBD], its two main aetiologies being iron deficiency anaemia [IDA] and anaemia of chronic inflammation [ACI]. Impaired intestinal iron absorption due to inflammatory cytokines is thought to play a role in ACI. We undertook for the first time a controlled prospective study investigating effects of differing underlying diseases, disease locations, and types of iron deficiency or anaemia on oral iron absorption in adult IBD patients with and without inflammation. METHODS: This study was a comparative, single-centred open clinical trial in adults with IBD [n = 73] and healthy controls [n = 22]. Baseline parameters included blood count, iron status [ferritin, transferrin, transferrin saturation, soluble transferrin receptor, hepcidin, serum iron], high-sensitivity C-reactive protein [hsCRP] and interleukin-6. Iron absorption was tested using one oral, enteric-coated capsule containing 567.7 mg iron[II]-glycine-sulphate complex. Serum iron was determined 60/90/120/180/240 min after ingestion. RESULTS: Iron absorption capacity was shown to be influenced by inflammation and anaemia or iron deficiency [ID] type but not by underlying disease type or localisation. The ACI group showed a significantly lower iron absorption capacity than all others. Whereas hsCRP levels [-0.387, p < 0.001], IL-6 [-0.331, p = 0.006], ferritin [-0.531, p < 0.001], and serum hepcidin [-0.353, p = 0.003] correlated negatively with serum iron change at 2 h, transferrin showed a positive correlation at the same time point [0.379, p < 0.001]. CONCLUSIONS: Underlying disease type and localisation appear to have little effect on iron absorption capacity, whereas lack of response to oral iron correlates well with serum markers of inflammation. Iron absorption capacity is thus significantly reduced in the presence of inflammation.

[Are there gender-related differences in the therapeutic management of patients suffering from inflammatory bowel disease? Subgroup analysis of a prospective multicentre online-based trial]. / Gibt es geschlechtsspezifische Behandlungsunterschiede bei Patienten mit chronisch entzündlichen Darmerkrankungen? Eine Subgruppenanalyse einer prospektiven, multizentrischen, online-basierten Studie.

INTRODUCTION: The most frequently prescribed medications for patients suffering from inflammatory bowel disease (IBD) in the Rhein-Main region of Germany are aminosalicylates and corticosteroids irrespective of the disease activity. In contrast, immunomodulators only play a marginal role. As anti-TNF therapy is very costly, it is prescribed in outpatient services of hospitals rather than in gastroenterological practices. AIM: The aim of this study was to evaluate possible gender-related differences in the therapeutic management of IBD patients treated in the Rhein-Main region of Germany. METHODS: Data records about past medical history, disease status, laboratory values and medical treatment of outpatients of 10 gastroenterological practices and 3 hospitals were collected from November 1st 2005 to July 31st 2007 and analysed with regard to gender-related differences in therapy and disease management. RESULTS: Overall, no statistically significant difference in gender-specific medical treatment could be observed in the study cohort. However, detailed analyses revealed, that 1. women suffering from IBD, who are treated in outpatient services of hospitals, are more often under immunosuppressants, irrespective of disease activity, 2. in gastroenterological practices less than 3 % of patients are prescribed any immunosuppressive therapy (vs. 17 % [men] und 42 % [women] in hospital outpatient services), and 3. anti-TNF therapy is applied more frequently in men as compared to women in hospital outpatient services in both remission and active disease. CONCLUSION: This study discloses the gender-specific differences in the therapeutic management of IBD patients in a congested urban area in Germany. Further studies are required to confirm the tendencies detected.

Health care and cost of medication for inflammatory bowel disease in the Rhein-Main region, Germany: a multicenter, prospective, internet-based study.

BACKGROUND: Studies examining the treatment reality of IBD patients in Germany have been limited, as networking among deliverers of care and reliable documentation of medical, demographic, and economic data are lacking. The aim of the present study was to establish an internet-based treatment registry in order to evaluate treatment of IBD patients in Germany. METHODS: Between November 1(st), 2005, and January 31, 2007, 1024 outpatients with prevalent IBD from 10 gastroenterological private practices and 3 hospitals (UC = 439, CD = 567, ID = 18) were enrolled in the study. An internet-based registry was established that included data about medical history, disease status, diagnostic procedures, laboratory test results, and medical treatment. Data for private practices and hospitals were pooled in order to compare treatment habits between these types of medical facilities. The cost of medication was determined according to medications prescribed. RESULTS: There was no significant difference between the 2 patient groups in demographic and clinical characteristics. Marked differences were observed in medical treatment. The most frequently prescribed medications in the private practices for patients in remission and those with active disease were aminosalicylates and corticosteroids. Immunomodulators played a marginal role. In contrast, in the hospitals azathioprine/6-MP was predominantly used for the maintenance of remission. Patients with fistulizing CD were treated with infliximab. The mean annual cost of medications was 1826 +/- 1331euro/patient (median 1353euro) in the private practices and 1849euro +/- 2897euro/patient (median 960euro) at the University Hospital. CONCLUSIONS: The registry provides the first detailed data about the reality of treatment of IBD patients in Germany and reveals the necessity for networking among attending physicians in order to implement guidelines-conformed treatment.

An expert consensus to standardise definitions, diagnosis and treatment targets for anti-fibrotic stricture therapies in Crohn's disease.

BACKGROUND: Fibrotic stricture is a common complication of Crohn's disease (CD) affecting approximately half of all patients. No specific anti-fibrotic therapies are available; however, several therapies are currently under evaluation. Drug development for the indication of stricturing CD is hampered by a lack of standardised definitions, diagnostic modalities, clinical trial eligibility criteria, endpoints and treatment targets in stricturing CD. AIM: To standardise definitions, diagnosis and treatment targets for anti-fibrotic stricture therapies in Chron's disease. METHODS: An interdisciplinary expert panel consisting of 15 gastroenterologists and radiologists was assembled. Using modified RAND/University of California Los Angeles appropriateness methodology, 109 candidate items derived from systematic review and expert opinion focusing on small intestinal strictures were anonymously rated as inappropriate, uncertain or appropriate. Survey results were discussed as a group before a second and third round of voting. RESULTS: Fibrotic strictures are defined by the combination of luminal narrowing, wall thickening and pre-stenotic dilation. Definitions of anastomotic (at site of prior intestinal resection with anastomosis) and naïve small bowel strictures were similar; however, there was uncertainty regarding wall thickness in anastomotic strictures. Magnetic resonance imaging is considered the optimal technique to define fibrotic strictures and assess response to therapy. Symptomatic strictures are defined by abdominal distension, cramping, dietary restrictions, nausea, vomiting, abdominal pain and post-prandial abdominal pain. Need for intervention (endoscopic balloon dilation or surgery) within 24-48 weeks is considered the appropriate endpoint in pharmacological trials. CONCLUSIONS: Consensus criteria for diagnosis and response to therapy in stricturing Crohn's disease should inform both clinical practice and trial design.

Functional interleukin-2 receptors on intestinal epithelial cells.

The presence of receptors for the cytokine IL-2 was assessed in the IEC-6 cell line established from normal rat crypt epithelium and primary intestinal epithelial cells. 125I-IL-2 was found to specifically bind to subconfluent IEC-6 cells. Maximal binding was observed within 30 min after addition of the ligand; binding could be inhibited by excess unlabeled IL-2 or addition of antibody to the IL-2 receptor. Both intermediate and low affinity receptors with approximate Kd of 10 and 100 pM, respectively were present. Kinetic analysis were consistent with the results of Western blot analysis using an antisera to the 75-kD IL-2 receptor beta chain. IL-2 receptors appeared to be functional; addition of IL-2 led to modulation of proliferation with initial stimulation at 24 h followed by inhibition at 48 h. This effect could be blocked by addition of antibody to the IL-2 receptor beta chain. IL-2 treatment could be shown to enhance expression (range = 4- to 50-fold stimulation) of TGF-beta, as well as the lectin protein mac-2, in IEC-6 cells. The relevance of observations in the IEC-6 cell line to intestinal mucosa in vivo was supported by the demonstration of a gradient of expression of the IL-2 receptor in primary rat intestinal epithelial cells by Western blot analysis. In addition, mRNA for the IL-2 receptor-beta chain was demonstrated by Northern blot analysis using mRNA from primary rat intestinal epithelial cells depleted of detectable contaminating intraepithelial lymphocytes by two cycles of fractionation on Percoll gradients. Collectively, these observations suggest that the range of cellular targets of the putative lymphokine IL-2 is broader than appreciated, and IL-2 may serve to integrate epithelial and lymphocyte responses in the intestinal mucosa.

Trefoil peptides promote epithelial migration through a transforming growth factor beta-independent pathway.

The trefoil peptides, a recently recognized family of protease-resistant peptides, expressed in a regional specific pattern throughout the normal gastrointestinal tract. Although these peptides have been hypothesized to act as growth factors, their functional properties are largely unknown. Addition of recombinant trefoil peptides human spasmolytic polypeptide (HSP), rat and human intestinal trefoil factor (RITF and HITF) to subconfluent nontransformed rat intestinal epithelial cell lines (IEC-6 and IEC-17), human colon cancer-derived cell lines (HT-29 and CaCO2) or nontransformed fibroblasts (NRK and BHK) had no significant effect on proliferation. However addition of the trefoil peptides to wounded monolayers of confluent IEC-6 cells in an in vitro model of epithelial restitution resulted in a 3-6-fold increase in the rate of epithelial migration into the wound. Stimulation of restitution by the trefoil peptide HSP was enhanced in a cooperative fashion by the addition of mucin glycoproteins purified from the colon or small intestine of either rat or man, achieving up to a 15-fold enhancement in restitution. No synergistic effect was observed by the addition of nonmucin glycoproteins. In contrast to cytokine stimulation of intestinal epithelial cell restitution which is mediated through enhanced TGF beta bioactivity, trefoil peptide, and trefoil peptide-mucin glycoprotein stimulation of restitution was not associated with alteration in concentrations of bioactive TGF-beta and was not affected by the presence of immunoneutralizing anti-TGF beta antiserum. Collectively, these findings suggest that the trefoil peptides which are secreted onto the lumenal surface of the gastrointestinal tract may act in conjunction with the mucin glycoprotein products of goblet cells to promote reestablishment of mucosal integrity after injury through mechanisms distinct from those which may act at the basolateral pole of the epithelium.