The taxonomic composition of the donor intestinal microbiota is a major factor influencing the efficacy of faecal microbiota transplantation in therapy refractory ulcerative colitis.

BACKGROUND: Faecal microbiota transplantation is an experimental approach for the treatment of patients with ulcerative colitis. Although there is growing evidence that faecal microbiota transplantation is effective in this disease, factors affecting its response are unknown. AIMS: To establish a faecal microbiota transplantation treatment protocol in ulcerative colitis patients, and to investigate which patient or donor factors are responsible for the treatment success. METHODS: This is an open controlled trial of repeated faecal microbiota transplantation after antibiotic pre-treatment (FMT-group, n = 17) vs antibiotic pre-treatment only (AB-group, n = 10) in 27 therapy refractory ulcerative colitis patients over 90 days. Faecal samples of donors and patients were analysed by 16SrRNA gene-based microbiota analysis. RESULTS: In the FMT-group, 10/17 (59%) of patients showed a response and 4/17 (24%) a remission to faecal microbiota transplantation. Response to faecal microbiota transplantation was mainly influenced by the taxonomic composition of the donor's microbiota. Stool of donors with a high bacterial richness (observed species remission 946 ± 93 vs no response 797 ± 181 at 15367 rps) and a high relative abundance of Akkermansia muciniphila (3.3 ± 3.1% vs 0.1 ± 0.2%), unclassified Ruminococcaceae (13.8 ± 5.0% vs 7.5 ± 3.7%), and Ruminococcus spp. (4.9 ± 3.5% vs 1.0 ± 0.7%) were more likely to induce remission. In contrast antibiotic treatment alone (AB-group) was poorly tolerated, probably because of a sustained decrease of intestinal microbial richness. CONCLUSIONS: The taxonomic composition of the donor's intestinal microbiota is a major factor influencing the efficacy of faecal microbiota transplantation in ulcerative colitis patients. The design of specific microbial preparation might lead to new treatments for ulcerative colitis.

The efficacy and safety of either infliximab or adalimumab in 362 patients with anti-TNF-α naïve Crohn's disease.

BACKGROUND: TNFα antagonists, including infliximab (IFX) and adalimumab (ADA), have revolutionised treatment for Crohn's disease. Studies comparing efficacy in patients with Crohn's disease naïve to TNFα antagonists are lacking. METHODS: Consecutive TNFα antagonist-naïve patients with luminal or perianal Crohn's disease from four tertiary centres in Austria were assessed prospectively for induction and maintenance efficacy, and safety, of either IFX or ADA. RESULTS: In a total of 362 patients, 251 (69.3%) started IFX and 111 (30.7%) started ADA. At baseline, the median Harvey-Bradshaw Index (HBI) score was 8 (range 5-29) and 8 (5-36), and the median C-reactive protein (CRP) was 1.07 (interquartile range (IQR) 1.36) mg/dL and 1.16 (IQR 1.23) mg/dL for IFX and ADA, respectively. At week 12, there was no difference between IFX and ADA among patients with luminal Crohn's disease in clinical remission (IFX 128/204; 62.7% vs. ADA 68/107; 63.6%, P = 0.47), clinical response (IFX 154/204; 75.5% vs. ADA 82/107; 76.6%, P = 0.82) and steroid-free remission (IFX 110/204; 53.9% vs. ADA 61/107; 57%, P = 0.60). At 12 months, there were similar numbers of patients treated with IFX and ADA who maintained clinical remission (IFX 77/154; 50.4% vs. ADA 47/82; 57.3%, P = 0.48) and steroid-free remission (IFX 68/154; 44.3% vs. ADA 44/82; 53.7%, P = 0.16). Baseline CRP >0.7 mg/dL (OR 0.24; 95% CI 0.07-0.77, P = 0.01) was the only predictor of clinical remission at 12 months in patients who did not have escalation of anti-TNFα therapy. CONCLUSION: IFX and ADA appear comparable in clinical outcomes for patients with Crohn's disease who are naïve to TNFα antagonists.

[Adalimumab for the treatment of ulcerative colitis--a consensus report by the working group inflammatory bowel diseases of the Austrian Society of Gastroenterology and Hepatology]. / Adalimumab in der Behandlung der Colitis ulcerosa--ein Konsensus der Arbeitsgruppe Chronisch Entzündliche Darmerkrankungen der Österreichischen Gesellschaft für Gastroenterologie und Hepatologie.

TNF alpha antibodies have clearly improved the outcome of moderately to severely active ulcerative colitis. Adalimumab is the first fully human, monoclonal TNF alpha antibody, which is administered subcutaneously. Since April 2012 adalimumab is approved for the treatment of moderately to severely active ulcerative colitis in patients who have not responded despite a full and adequate course of therapy with a corticosteroid and an immunosuppressant or who are intolerant to or have medical contraindications for such therapies. Adalimumab can induce and maintain clinical remission and mucosal healing compared to placebo in moderately to severely active ulcerative colitis, can reduce the rate of ulcerative colitis related hospitalisations and improve health-related quality of life. The response can be observed after two weeks of treatment. The safety profile of adalimumab is comparable to those of other TNF alpha inhibitors. Studies on the treatment of ulcerative colitis with adalimumab did not reveal new safety aspects. The present consensus report by the Working Group Inflammatory Bowel Diseases of the Austrian Society of Gastroenterology and Hepatology presents the existing evidence of adalimumab for the treatment of ulcerative colitis and is aimed to assist as code of its practice.

[Adalimumab for the treatment of adult Crohn's disease--update of a consensus report by the Working Group Inflammatory Bowel Disease of the Austrian Society of Gastroenterology and Hepatology]. / Adalimumab in der Behandlung des adulten Morbus Crohn--Update eines Konsensus der Arbeitsgruppe Chronisch Entzündliche Darmerkrankungen der Österreichischen Gesellschaft für Gastroenterologie und Hepatologie.

TNF alpha antibodies have clearly improved the outcome of moderate to severe Crohn's disease. Adalimumab is the first fully human, monoclonal TNF alpha antibody, which can be self-administered subcutaneously. Since August 2012 adalimumab is approved for the treatment of moderately to severely active Crohn's disease, in patients who have not responded despite a full and adequate course of therapy with a corticosteroid and/or an immunosuppressant or who are intolerant to or have medical contraindications for such therapies. Compared to placebo adalimumab can induce significantly more often steroid-free remission and mucosal healing in patients with moderate to severe Crohn's disease, reduce the rate of Crohn's disease-related hospitalisations and surgery and improve health-related quality of life. Adalimumab is clinically efficacious both in patients with Crohn's disease naïve to previous exposure to TNF-alpha antibodies and in those previously exposed with a rapid onset of action within days and confirmed maintenance performance over 3 years. The safety profile of adalimumab is comparable to those of other TNF alpha inhibitors. Due to its low immunogenicity allergic reactions are rare. The update of a consensus report by the Working Group Inflammatory Bowel Disease of the Austrian Society of Gastroenterology and Hepatology presents the existing evidence on adalimumab for the treatment of Crohn's disease and is aimed to assist as a code of practice in its applications.

Incidence of inflammatory bowel disease in the province of Styria, Austria, from 1997 to 2007: a population-based study.

BACKGROUND: The incidence of inflammatory bowel disease (IBD) varies widely between different countries. This large variation is also observed for the incidence of its main two forms, ulcerative colitis (UC) and Crohn's disease (CD). Controversy exists whether IBD incidence is increasing, especially in western countries. Currently no data are available for Austria. This study therefore aimed to evaluate for the first time the incidence of IBD over an eleven-year period in Styria, a province of Austria with a population of 1.2 million. METHODS: All patients with an initial diagnosis of IBD between 1997 and 2007, who were Styrian residents, were eligible for this retrospective study. Data were acquired from electronically stored hospital discharge reports and individual reports by patients and physicians. According to population density Styria was divided into two rural and one urban area. RESULTS: Throughout the study period 1527 patients with an initial diagnosis of IBD were identified. The average annual incidence was 6.7 (95% CI 6.2-7.1) per 100,000 persons per year for CD and 4.8 (95% CI 4.5-5.2) for UC. The average annual incidence increased significantly (p<0.01) for both diseases during the 11 year study period. Median age at initial diagnosis was 29 years (range 3-87) for CD and 39 years (range 3-94) for UC. At diagnosis, 8.5% of all IBD patients were <18 years of age. The incidence of both CD and UC was significantly higher in the urban area than in rural areas (CD: 8.8, 95% CI 7.8-9.8 versus 5.5, 95% CI 4.7-6.4 and 5.9, 95% CI 5.3-6.7; [p<0.001]; UC: 5.8, 95% CI 5.1-6.6 versus 4.0, 95% CI 3.4-4.7 and 4.7, 95% CI 4.1-5.4; [p=0.04]). CONCLUSION: We observed an overall increase in the incidence of ulcerative colitis and Crohn's disease in a part of Austria during an eleven year period. IBD was more predominant in the largest urban area than in rural areas.

Knotting of percutaneous endoscopic jejunostomy feeding tubes in two patients with Parkinson's disease and continuous Duodopa® treatment.

Continuous intraduodenal infusion of levodopa/carbidopa (Duodopa®) via PEJ tubes is increasingly used in patients with advanced stages of Parkinson's disease. Tube-related complications such as kinking or coiling have been frequently reported. We herein describe two cases of tube dysfunction in patients with Parkinson's disease and continuous Duodopa® treatment due to knotting of the distal end of the tube. The mechanisms of knotting are unclear although a causative role of impaired gastrointestinal motility either by Parkinson's disease itself or Duodopa® treatment might be suspected.

[Diagnosis and treatment of iron deficiency and anaemia in inflammatory bowel diseases. Consensus of the Austrian IBD Working Party]. / Diagnose und Behandlung von Eisenmangel und Anämie bei chronisch entzündlichen Darmerkrankungen. Konsensus der österreichischen Arbeitsgruppe für CED.

Iron deficiency with and without anaemia is a common burden of patients with inflammatory bowel diseases (IBD) and has considerable impact on their quality of life and the ability to perform. The IBD working group of the Austrian Society of Gastroenterology and Hepatology developed five consensus statements on the following topics: (i) diagnosis of iron deficiency and (ii) anaemia, (iii) screening of iron deficiency, (iv) treatment of iron deficiency and (v) therapeutic goals. The clinical importance of intravenous iron replacement therapy in IBD with regard to effectiveness and compliance was discussed.

[Infliximab therapy for Crohn's disease - a practical guideline: actualised consensus of the working group for chronic inflammatory bowel diseases of the Austrian Society for Gastroenterology and Hepatology]. / Infliximab in der Therapie des Morbus Crohn - ein praktischer Leitfaden: aktualisierter ÖGGH-Konsensus der Arbeitsgruppe Chronisch-entzündliche Darmerkrankungen der ÖGGH.

Infliximab is a monoclonal antibody against tumor necrosis factor alpha (TNF-α), which is approved for the treatment of chronic inflammatory bowel disease (IBD) such as Crohn's disease (CD), fistulating Crohn's disease (FCD), ulcerative colitis (UC), and paediatric ulcerative colitis (PUC) from 6 years onwards. Besides its therapeutic efficacy, this antibody therapy is characterised by its side effects profile, which has been addressed in a seperate consensus statement by the Working Group for chronic inflammatory bowel diseases within the Austrian Society for Gastroenterology and Hepatology. Infliximab is an effective treatment option for the above-mentioned indications; however, use of this agent requires special knowledge to assess the benefit-risk profile for each patient individually.

A decade of infliximab: The Austrian evidence based consensus on the safe use of infliximab in inflammatory bowel disease.

Infliximab (IFX) has tremendously enriched the therapy of inflammatory bowel diseases (IBD) and other immune mediated diseases. Although the efficacy of IFX was undoubtedly proven during the last decade numerous publications have also caused various safety concerns. To summarize the immense information concerning adverse events and safety issues the Austrian Society of Gastroenterology and Hepatology launched this evidence based consensus on the safe use of IFX which covers the following topics: infusion reactions and immunogenicity, skin reactions, opportunistic infections (including tuberculosis), non-opportunistic infections (bacterial and viral), vaccination, neurological complications, hepatotoxicity, congestive heart failure, haematological side effects, intestinal strictures, stenosis and bowel obstruction (SSO), concomitant medication, malignancy and lymphoma, IFX in the elderly and the young, mortality, fertility, pregnancy and breast feeding. To make the vast amount of information practicable for routine application the consensus was finally condensed into a checklist for a safe use of IFX which consists of two parts: issues to be addressed prior to anti-TNF therapy and issues to be addressed during maintenance. Both parts are further divided into obligatory and facultative items.

[Adalimumab for the treatment of Crohn's disease - consensus paper of the Working Group "chronic inflammatory bowel diseases" of the Austrian Society for Gastroenterology and Hepatology]. / Adalimumab in der Behandlung des Morbus Crohn - ein Konsensus der Arbeitsgruppe Chronisch Entzündliche Darmerkrankungen der Osterreichischen Gesellschaft für Gastroenterologie und Hepatologie.

The advent of anti-TNF alpha antibodies has clearly improved the outcome of patients with Crohn's disease. With adalimumab, the first fully human, monoclonal anti-TNF alpha antibody, which can be administered subcutaneously by means of a pen, became available in 2007. In Europe adalimumab is approved for the treatment of severe, active Crohn's disease, in patients who have not responded despite a full and adequate course of therapy with a corticosteroid and/or an immunosuppressant; or who are intolerant to or have medical contraindications for such therapies. Adalimumab is clinically efficacious both in patients with Crohn's disease naïve to previous exposure to anti-TNF alpha antibodies and in those previously exposed with a rapid onset of action and a confirmed maintenance performance over 3 years. A reduction in the rate of hospitalisation and an improvement of health-related quality of life are associated with this treatment. The safety profile of adalimumab is comparable to those of other TNF alpha inhibitors. Due to low immunogenicity, allergic reactions are rare. A careful screening of patients before and during treatment with adalimumab is of key importance. The presented therapy guidelines based on existing evidence are aimed to assist in the efficient and safe use of adalimumab in the treatment of Crohn's disease.

[Use of infliximab in ulcerative colitis]. / Infliximab in der Therapie der Colitis ulcerosa.

Infliximab, a chimeric monoclonal anti-tumour necrosis factor alpha (TNF) antibody has dramatically changed the management of various chronic inflammatory disorders such as Crohn's disease (CD), rheumatoid arthritis, ankylosing spondylitis or psoriasis. This drug is well established for the treatment of CD in case of steroid-refractoriness, failure to respond to an immunosuppressant agent or fistulizing disease. The immunological concept that ulcerative colitis (UC) reflects primarily a T-helper cell type-2 mediated disease prevented the earlier use of anti-TNF agents in this disease. Promising initial pilot studies in steroid-refractory UC patients led to two large placebo-controlled trials in patients with moderate to severe UC. These studies clearly showed a benefit for infliximab treatment in UC with mucosal healing and improved life quality. Infliximab therefore can be used in patients not responding adequately to steroids and/or immunosuppressants. Furthermore, one study showed evidence that infliximab might also be effective in severe, intravenous steroid-refractory UC. Therefore, infliximab might be used alternatively to cyclosporine A or tacrolimus in this patient group. Infliximab has now been established as an additional treatment option in patients with chronic-active UC not responding to an immunosuppressive agent and/or in case of severe acute UC. Experienced gastroenterologists should be involved in the decision making for such a therapy to balance thoroughly the benefit/risk ratio for our patients.

[Endoscopy in IBD. A Consensus Report of the IBD Working of the Austrian Association of Gastroenterology and Hepatology]. / Endoskopie bei CED.

Ileocolonoscopy including biopsies is the first line investigation in suspected inflammatory bowel disease (IBD). In up to 90 % of the cases ulcerative colitis and Crohn's disease are differentiated on endoscopic presentation. Standardised reporting of endoscopic results increases the validity and comparability of IBD findings. When there is a firm diagnosis of IBD, colonoscopy should only be performed for specific questions. An upper gastrointestinal endoscopy is only indicated in patients with upper gastrointestinal symptoms. Push and capsule endoscopy should also be limited to specific questions and situations. IBD with extended colitis is associated with an increased risk for colorectal cancer. Endoscopic surveillance with accurate biopsy sampling is a valuable tool for the prevention of colorectal cancer.

[Aminosalicylates and steroids in the treatment ot chronic inflammatory bowel diseases--consensus paper of the Working Group for Chronic Inflammatory Bowel Diseases of the OGGH]. / Aminosalicylate und Steroide in der Behandlung von chronisch entzündlichen Darmerkrankungen -- Konsensuspapier der Arbeitsgruppe für chronisch entzündliche Darmerkrankungen der OGGH.

5-aminosalicylates (5-ASA) and steroids constitute a cornerstone of medical therapy in patients with inflammatory bowel diseases (IBD). Whereas the efficacy of 5-ASA in Crohn's disease (CD) is equivocal, ulcerative colitis (UC) is the main indication for this drug. In UC, 5-ASA is effective in the treatment of mild to moderate acute disease and in maintenance of remission. Furthermore, 5-ASA topical therapy is an important treatment option in patients with mild to moderate proctitis and/or left-sided UC and shows additive efficacy to oral therapy. From retrospective data a chemo-preventative activity of long-term 5-ASA therapy in UC is delineated. Steroids are treatment of first choice for moderate to severe cases of CD and UC. Budesonide, a modified steroid with less side effects, plays a major role in the treatment of ileocolonic CD +/- involvement of the right colon and is used as treatment of choice in mild-to-moderate cases. In case of acute, severe disease conventional steroids are superior compared to budesonide and therefore budesonide should only be used after considerable improvement of disease activity. The necessity to apply steroids in a given patient represents a negative prognostic indicator for the course of disease and should incite the early introduction of immunosuppressive therapy in this case. Steroids are only effective as short term therapy of IBD and are to be avoided for maintenance treatment. In all cases of steroid therapy an osteoporosis prophylaxis with calcium and vitamin D is recommended. Topical steroid treatment is less effective in left-sided UC compared to 5-ASA.

6-Thioguanine treatment in inflammatory bowel disease: a critical appraisal by a European 6-TG working party.

Recently, the suggestion to use 6-thioguanine (6-TG) as an alternative thiopurine in patients with inflammatory bowel disease (IBD) has been discarded due to reports about possible (hepato) toxicity. During meetings arranged in Vienna and Prague in 2004, European experts applying 6-TG further on in IBD patients presented data on safety and efficacy of 6-TG. After thorough evaluation of its risk-benefit ratio, the group consented that 6-TG may still be considered as a rescue drug in stringently defined indications in IBD, albeit restricted to a clinical research setting. As a potential indication for administering 6-TG, we delineated the requirement for maintenance therapy as well as intolerance and/or resistance to aminosalicylates, azathioprine, 6-mercaptopurine, methotrexate and infliximab. Furthermore, indications are preferred in which surgery is thought to be inappropriate. The standard 6-TG dosage should not exceed 25 mg daily. Routine laboratory controls are mandatory in short intervals. Liver biopsies should be performed after 6-12 months, three years and then three-yearly accompanied by gastroduodenoscopy, to monitor for potential hepatotoxicity, including nodular regenerative hyperplasia (NRH) and veno-occlusive disease (VOD). Treatment with 6-TG must be discontinued in case of overt or histologically proven hepatotoxicity.

[Immunosuppressive therapy for inflammatory bowel disease: consensus by the Austrian working group on IBD]. / Immunsuppressiva in der Therapie chronisch entzündlicher Darmerkrankungen. Konsensus der Arbeitsgruppe Chronisch Entzündliche Darmerkrankungen der OGGH.

Azathioprine (AZA) or 6-mercaptopurine (6-MP) are the immunosuppressive drugs of choice in the treatment of inflammatory bowel disorders (IBD). Optimal dosage for AZA is around 2.5 mg/kg body weight and induction of remission by these drugs may take 6 - 7 months. Intramuscularly applied Methotrexate (MTX) is the second choice, while its efficacy starts earlier than that of AZA; studies assessing oral low-dose MTX treatment are lacking. Cyclosporin is the standard treatment in case of steroid-refractory severe ulcerative colitis. This drug may also be used in patients with severe extraintestinal manifestations of IBD. Regarding other immunosuppressive drugs such as mycophenolic acid or 6-thioguanine respective controlled clinical study data are not available. The risk of malignancy using immunosuppressive drugs such as AZA is low and furthermore, especially AZA and 6-MP can be used rather safely during pregnancy.