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.

[Recommendations for the use of faecal microbiota transplantation "stool transplantation": consensus of the Austrian Society of Gastroenterology and Hepatology (ÖGGH) in cooperation with the Austrian Society of Infectious Diseases and Tropical Medicine]. / Empfehlungen zur Anwendung der fäkalen Mikrobiotatransplantation "Stuhltransplantation": Konsensus der Österreichischen Gesellschaft für Gastroenterologie und Hepatologie (ÖGGH) in Zusammenarbeit mit der Österreichischen Gesellschaft für Infektiologie und Tropenmedizin (OEGIT).

The intestinal microbiota has a pivotal role in the maintenance of health of the human organism, especially in the defense against pathogenic microorganisms. Alterations in the microbiota, also termed dysbiosis, seem to be involved in the pathogenesis of a variety of intestinal and extraintestinal diseases. Fecal microbiota transplantation (FMT), also known as stool transplantation, is a therapeutic procedure aiming at restoring an altered intestinal microbiota by administration of stool microorganisms from a healthy donor into the intestinal tract of a patient. FMT is most commonly used for recurrent forms of Clostridium difficile infections (CDI). There are currently many cohort studies in a large number of patients and a randomized controlled trial showing a dramatic effect of FMT for this indication. Therefore FMT is recommended by international medical societies for the treatment of recurrent CDI with high scientific evidence. Other potential indications are the treatment of fulminant CDI or the treatment of inflammatory bowel diseases. In the practical utilization of FMT there are currently several open questions regarding the screening of stool donors, the processing of stool and the mode of FMT application. Different modes of FMT application have been described, the application into the colon has to be preferred due to less reported side effects than the application into the upper gastrointestinal tract. So far only very few side effects due to FMT have been reported, nevertheless the use and risks of FMT are currently intensely debated in the medical community. This consensus report of the Austrian society of gastroenterology and hepatology (ÖGGH) in cooperation with the Austrian society of infectious diseases and tropical medicine provides instructions for physicians who want to use FMT which are based on the current medical literature.

[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.

[Colorectal cancer: screening and surveillance in inflammatory bowel diseases - consensus of the working group for inflammatory bowel diseases of the Austrian Society of Gastroenterology and Hepatology]. / Kolorektales Karzinom: Screening und Surveillance bei chronisch entzündlichen Darmerkrankungen - Konsensus der Arbeitsgruppe für chronisch entzündliche Darmerkrankungen der ÖGGH.

Patients with ulcerative colitis and Crohn's colitis are at increased risk of colorectal cancer (CRC). This risk is dependent on the duration and extent of disease, inflammatory activity and possible additional risk factors. Thus, the aim is to reduce this risk and to detect dysplastic and malignant lesions at an early stage. The working group for Inflammatory Bowel Diseases (IBD) of the Austrian Society of Gastroenterology and Hepatology (ÖGGH) has developed consensus statements on the following topics: risk of colorectal cancer, screening and surveillance, procedure of surveillance colonoscopy, dysplasia and its management, and chemoprevention. This consensus is intended to increase awareness of the increased risk of CRC in IBD and to support a standardised approach in cancer prevention.

Retesting for latent tuberculosis in patients with inflammatory bowel disease treated with TNF-α inhibitors.

BACKGROUND: Patients treated with TNF-α inhibitors (TNFi) are at high risk of reactivation of latent tuberculosis (LTB). Prospective studies on monitoring of TB reactivation and/or infection in this risk group are lacking. AIM: To test the conversion and reversion rate of screening tests for latent TB serial tuberculin skin test (TST) and interferon-γ release assay (IGRA) under ongoing TNFi therapy. METHODS: We retested consecutive patients with IBD receiving TNFi therapy for a minimum of 5 months for LTB using IGRA and TST. A detailed patient history and concomitant therapy were recorded for each subject. RESULTS: After a median of 34.9 weeks (20.7­177.7), IGRA was retested in 184/227 patients (81.1%; Crohn's disease n = 139, ulcerative colitis n = 45) still under index TNFi. TST was available in 144/184 subjects (78.2%). The majority of patients were TNFi naïve (147/184, 79.9%). In a subgroup of patients who received isoniazid due to diagnosis of latent TB at baseline (n = 32), 6/13 patients (46.2%) with baseline positive IGRA and 3/22 patients (13.6%) with baseline positive TST reverted to negative at retesting. In patients without diagnosis of LTB at baseline no permanent IGRA conversion was observed, but there were 6/144 (4.2%) TST conversions from negative to positive. No single case of TB reactivation or infection was recorded during the observation period. CONCLUSIONS: During treatment TNF-α inhibitors conversion was observed for tuberculin skin test, but not interferon-γ release assay. As compared with tuberculin skin test, interferon-γ release assay reverted in nearly half of isoniazid-treated patients for latent tuberculosis. However, the fact that patients in whom the interferon-γ release assay test result remained positive did not develop active tuberculosis during follow-up questions the utility of interferon-γ release assay as a monitoring tool during chemoprevention.

The impact of intestinal resection on serum levels of anti-Saccharomyces cerevisiae antibodies (ASCA) in patients with Crohn's disease.

BACKGROUND: Antibodies to Saccharomyces cerevisiae (ASCA) are highly prevalent in sera of patients with Crohn's disease and have been proposed to identify subgroups of patients with a disabling disease course. AIM: To investigate the impact of intestinal resection on serum levels of ASCA in patients with Crohn's disease and the predictive value of ASCA levels on surgical recurrence. METHODS: Sera from 60 patients who underwent 'curative' intestinal resection due to stricturing and/or penetrating complications were collected preoperatively and during post-operative follow-up (week 2, months 4, 8 and 11 ± 1). Measurement of ASCA IgG and IgA isotypes were performed using ELISA. Re-operation rate was associated with ASCA status and serum levels. RESULTS: At baseline 44/60 (73%) of patients were rated as positive for ASCA IgG, 45/60 (75%) for ASCA IgA and 52/60 (87%) as positive for at least one of both. ASCA serum levels remained stable during first year from resection. After a median of 106 months 10 of 40 (25%) patients with long-term follow-up underwent one or more intestinal re-operations. Neither ASCA positivity nor absolute ASCA serum levels were predictive of surgical recurrence. CONCLUSIONS: Serum ASCA levels remain stable after curative intestinal resection in Crohn's disease. This indicates the persistence of both stimulus and immunological mechanism operative in the production of ASCA even after complete surgical resection of macroscopically inflamed intestinal tissue. After intestinal resection, neither ASCA positivity nor ASCA serum levels predict the risk of surgical recurrence during long-term follow-up.

[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.

Efficacy and safety of antiviral therapy in patients with Crohn's disease and chronic hepatitis C.

BACKGROUND: Efficacy and safety of antiviral combination therapy in patients with Crohn's disease (CD) and chronic hepatitis C (CHC) is presently not established and consequently CHC is rarely treated in CD patients. AIM: To analyse the efficacy and tolerability of antiviral interferon/ribavirin therapy in patients with CHC and CD. METHODS: Eleven HCV-infected CD patients received either 3 x 1.5 microg/kg/week interferon-alpha-2b or 180 microg/week peginterferon-alpha-2a (PEGASYS; Roche, Basel, Switzerland) as monotherapy (n = 1) or in combination with 800-1200 mg/day ribavirin (COPEGUS; Roche) (n = 10) for 24-54 weeks according to HCV-genotype and initial response respectively. Eight patients were under CD-specific therapy. RESULTS: Five (46%) patients (HCV-1: a = 3; HCV-2: n = 0; HCV-3: n = 1; unknown: n = 1) achieved a sustained virological response, three (27%) patients relapsed, three (27%) were nonresponders (all GT 1b). At baseline, the Harvey--Bradshaw Index was 0 (0-8) [median (range)], increased on antiviral therapy to 4 (1-15) (P = 0.005) and decreased to baseline level 0 (0-6) after 6-month follow-up. CONCLUSIONS: This preliminary experience demonstrates that treatment of CHC in patients with CD is comparable to the treatment of CHC in those without CD. However, gastrointestinal symptoms may be temporarily exacerbated and haemopoietic growth factors may be required.

A clinical trial on absorption and N-acetylation of oral and rectal mesalazine.

BACKGROUND: Mesalazine (5-ASA) is a standard treatment for ulcerative colitis. Extent of absorption and N-acetylation determine systemic exposure to 5-ASA, and are thereby relevant for the safety of the treatment. The aim of the study was to compare absorption and N-acetylation of 5-ASA following rectal or oral drug administration. Healthy subjects were compared to patients with ulcerative colitis to evaluate the impact of chronic inflammation of colorectal mucosa on disposition of 5-ASA. MATERIALS AND METHODS: First, 12 healthy adults were randomized to receive 2 g of 5-ASA by each of four different formulations: oral delayed release granules, 30 mL enema, 60 mL rectal foam, and 120 mL rectal foam. Second, 12 patients with active ulcerative colitis received 60 mL rectal foam. Pharmacokinetic analysis was performed by determination of 5-ASA and its acetylated, pharmacologically inactive metabolite (Ac-5-ASA) in plasma and urine. RESULTS: First, systemic exposure to 5-ASA was markedly lower after rectal drug administration as compared to oral dosing (P < 0.001; e.g. median relative bioavailability of 60 mL rectal foam: 36%). Second, N-acetylation of rectal 5-ASA was lower in patients than in healthy subjects [area under the curve (AUC) ratio Ac-5-ASA/5-ASA: 1.6 +/- 0.5 vs. 2.3 +/- 0.4, mean +/- SD, P < 0.01]. High peak plasma concentrations of 5-ASA were correlated with high microscopic disease activity (r = 0.67, P < 0.05). CONCLUSIONS: Rectal delivery of 5-ASA results in low systemic drug exposure with potentially reduced toxicity in comparison with oral drug administration. Chronic inflammation of colorectal mucosa might be a relevant source of variability in pharmacokinetics of 5-ASA.

Is inflammatory bowel disease an independent and disease specific risk factor for thromboembolism?

BACKGROUND: Patients with inflammatory bowel disease (IBD) are thought to be at increased risk of venous thromboembolism (TE). However, the extent of this risk is not known. Furthermore, it is not known if this risk is specific for IBD or if it is shared by other chronic inflammatory diseases or other chronic bowel diseases. AIMS: To compare the risk of TE in patients with IBD, rheumatoid arthritis, and coeliac disease with matched control subjects. PATIENTS AND METHODS: Study subjects answered a questionnaire assessing the history of TE, any cases of which had to be confirmed radiologically. A total of 618 patients with IBD, 243 with rheumatoid arthritis, 207 with coeliac disease, and 707 control subjects were consecutively included. All three patient groups were compared with control subjects matched to the respective group by age and sex. RESULTS: Thirty eight IBD patients (6.2%) had suffered TE. This was significantly higher compared with the matched control population with only 10 cases reported (1.6%) (p<0.001; odds ratio (OR) 3.6 (95% confidence interval (CI) 1.7-7.8)). Five patients with rheumatoid arthritis (2.1%) had suffered TE compared with six subjects (2.5%) in the control population matched to patients with rheumatoid arthritis (NS; OR 0.7 (95% CI 0.2-2.9)). TE had occurred in two patients with coeliac disease (1%) compared with four subjects (1.9%) in the control population matched to the coeliac disease group (NS; OR 0.4 (95% CI 0.1-2.5)). In 60% of TE cases in the IBD group, at least one IBD specific factor (active disease, stenosis, fistula, abscess) was present at the time TE occurred. CONCLUSIONS: IBD is a risk factor for TE. It seems that TE is a specific feature of IBD as neither rheumatoid arthritis, another chronic inflammatory disease, nor coeliac disease, another chronic bowel disease, had an increased risk of TE.

Giant benign cystic mesothelioma: a case report and review of literature.

A 28-year-old man was admitted because of weight loss and a huge abdominal mass. The abdominal cavity was filled by a large number of cysts with a maximum diameter of 10 cm as diagnosed by ultrasound and computed tomography. Laparotomy was performed and a 33 kg cystic tumour originating from the peritoneum was resected en bloc. Histopathological work-up showed multiple cysts covered by cubic or flat mesothelial cells with uniform nuclei. The final diagnosis was benign cystic mesothelioma. Twenty-three months after surgical debulking, a follow-up computed tomography scan showed recurrence of the disease. In this report, we describe the characteristics, aetiology and differential diagnosis of this rare lesion.