Abstract Background Anti-TNF therapy is still the most frequently used first-line biologic treatment in inflammatory bowel disease (IBD). This study aimed to determine length of treatment persistence and to describe reasons for discontinuation of first-line anti-TNF therapy used in the standard care of IBD patients. Methods A single-center, real-world, retrospective study including IBD patients (Crohn’s disease (CD), ulcerative colitis (UC), IBD unclassified (IBD-U)), who received an anti-TNF therapy in the last 20 years at the study center, was conducted. Length of first-line anti-TNF therapy, differences in treatment duration between infliximab (IFX) and adalimumab (ADA) and between CD and UC, reasons for discontinuation, side effects leading to cessation, treatment following first-line anti-TNF therapy, rates of surgery and death, and factors being associated with treatment failure were assessed. Results 586 patients were identified as having received first-line anti-TNF therapy at the study center. 48 patients were excluded due to shortness of available data. 538 patients (CD: 367, UC: 147, IBD-U: 24) with a median follow-up of 8.1 years were included in the analysis. Median (IQR) treatment persistence was 21.0 (6.0, 57.0) months in the total cohort. Treatment withdrawal arose frequently (40%) within the first year of therapy and treatment persistence was longer in CD compared to UC (CD: 27.0 (8.0, 71.0) months, UC: 11.0 (3.0, 34) months, p<0.001). Treatment failure (51%) and side effects (24%) were the most commonly noticed reasons for withdrawal from therapy. 14% withdrew from therapy due to remission. The diagnosis of UC, female sex, the absence of prior intestinal resections, lower hemoglobin and albumin levels at anti-TNF initiation predicted treatment failure. Patients with CD continued ADA treatment longer than IFX treatment (ADA: (40.5 (14.2, 80.5) months, IFX: 18.0 (4.8, 65.0) months, p<0.001). Within the follow-up period, 17% of UC patients underwent colectomy and 34% of CD patients had at least one intestinal resection after start of first-line anti-TNF therapy. 2% of all patients died due to various reasons. Conclusion Treatment persistence of first-line anti-TNF therapy is limited in IBD patients due to a large proportion of treatment failures and side effects.

Double-blind randomised studies investigating faecal microbiota transplantation (FMT) in chronic active ulcerative colitis (UC) have shown promising results so far. Factors influencing the efficacy of FMT in UC still remain unclear. FMT protocols for the treatment of UC patients vary in dose, frequency, route of application and donor stool preparation and might thus influence remission rates. The aim of this analysis was to find clinical predictors for non-response to FMT in UC. 54 patients suffering from chronic active ulcerative colitis were treated with repeated FMT (5 times every second week) using the same protocol with the exception of donor stool preparation. Thirty patients (mean age 37 y ± 9) were treated with frozen donor stool (mixed with sodium chloride and glycerol, stored at −80°C) and 24 patients (mean age 43 y ± 14) with freshly prepared donor stool (not older than 6 h). Remission and response were determined by total Mayo score (TMS) before FMT and at Day 90. Clinical response was defined as a decrease of ≥3 points in TMS from baseline, along with either a decrease of >1 point in the rectal bleeding subscore or the absolute rectal bleeding subscore of 0 or 1. Remission was defined as a TMS <2 and an endoscopic subscore of 0 or 1. Clinical data as well as blood and stool analysis were assessed at any time point and potential predictors for non-response were calculated using regression analysis. At baseline patients had a total Mayo score of 9.0 ± 2.0 and an endoscopic subscore of 2.5 ± 1.0. 65% of patients had failed previous biologic therapy and 70% previous immunosuppressive treatment. In total 59% of patients responded to FMT, 24% achieved remission while 41% showed no response. The mean total Mayo score dropped to 5.3 ± 3.2 at Day 90. Non-response to biologics (hazard ratio (HR): 0.23 (95% CI 0.06–0.85), p: 0.03), a total Mayo score before FMT ≥9 (HR: 0.26 (95% CI 0.07–0.95), p: 0.04) and a high endoscopic subscore before FMT (HR: 0.27 (0.10–0.69, p < 0.01) were associated with lower remission rates. There was no significant difference in decrease of TMS (p = 0.51) or in remission and response rates (p = 0.97), respectively in patients receiving fresh or frozen donor stool at Day 90. Failure to previous biologic treatment as well as a high total Mayo score and a high endoscopic subscore are associated with lower remission rates to FMT in chronic active ulcerative colitis.

Patients with inflammatory bowel disease (IBD) are at increased risk of first and recurrent venous thromboembolism (VTE). Anticoagulation (AC) is the standard treatment of VTE, but might lead to bleeding complications. We sought to investigate if the bleeding rate is increased during episodes with AC in patients with IBD and VTE. In a previous study 157 IBD patients with objectively diagnosed VTE were identified. From these patients 107 were included in the analysis. Data were recorded from the medical records and by interviewing the patients via a phone call. The primary end point was the occurrence of a severe bleeding complication, which was defined as a fatal bleeding or a symptomatic bleeding in a critical organ (e.g. intracerebral bleeding) or a bleeding leading to a loss of haemoglobin of ≥20 g l−1or leading to a transfusion of ≥2 red cell packages (RCP). The study is a sequential therapy comparison, in which the bleeding rate in the same patient during episodes under and without AC was compared. Patients contributed episodes with and without AC with variable length. The unit of analysis was each episode. To allow for this longitudinal data structure we used regression models with weighting for the length of each separate episode and based the calculation of 95% confidence intervals and p-values on cluster robust standard errors with patients ID as the identifier. Anticoagulation yes vs. no was the main covariate. For binary outcomes we used logistic models , otherwise we used linear models. To adjust for other clinically predetermined influential variables we used multivariable regression models. A total of 195 episodes without AC and 144 episodes under AC were observed. 21 major bleedings occurred. 10 under AC (5 under heparin and 5 under vitamin-K antagonist treatment) (8: transfusion of ≥2 RCP; 2: loss of haemoglobin of ≥ 20 g l-1) and 11 without AC (8: transfusion of ≥2 RCP; 2: loss of haemoglobin of ≥20 g l-1; 1: death) (Table 1). Major bleeding complications did not occur more often in time periods under AC than in time periods without AC using Fisher’s exact test (p = 0.65). This was confirmed by logistic regression (Table 2). Number of major bleeding complications in time periods under and without anticoagulation treatment (AC). Number of major bleeding complications in time periods under and without anticoagulation treatment (AC). Logistic regression for major bleeding complications. Logistic regression for major bleeding complications. Our data suggest that anticoagulant treatment after VTE does not increase the risk of major bleeding complications in patients with IBD.

Anhand doppelblinder, randomisierter Studien konnte kürzlich die Überlegenheit der fäkalen Mikrobiota-Transplantation (FMT) im Vergleich zu Placebo bei der Behandlung der aktiver Colitis ulcerosa (CU) gezeigt werden. Durch unterschiedliche Ergebnisse bei verschiedenen FMT-Protokollen sind jedoch hierfür noch viele Fragen offen. Die Verwendung von gefrorenem Spenderstuhl zur FMT bei Clostridium difficile-Infektionen hat sich als genauso wirksam erwiesen wie frischer Spenderstuhl. Das Ziel dieser Studie war es, die klinische Wirksamkeit von gefrorenem Stuhl für die FMT auch bei Colitis ulcerosa zu untersuchen.

Crohn's Disease (CD), a chronic medical condition characterized by relapsing and remitting gastrointestinal inflammation, frequently affects health-related quality of life (HRQL). Restoration of HRQL is a major therapy endpoint but rarely assessed routinely. Thus, little is known on the effect of immunosuppressives and biologics on HRQL.

SummaryBackgroundFaecal 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.AimsTo 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.MethodsThis 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.ResultsIn 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.ConclusionsThe 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.

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.

Introduction: Crohn's disease (CD) is frequently accompanied by mental disorders including anxiety or depression. This study explores if adalimumab (ADA) is not only effective for CD but shows positive effects on anxiety as well.

Hintergrund: C. difficile wird bei CED-Patienten häufiger nachgewiesen als bei Personen, die nicht an einer CED erkrankt sind.

Hintergrund: Das Auftreten einer sekundären Amyloidose ist eine seltene, schwerwiegende Komplikation des Morbus Crohn (MC) und mit einer sehr ungünstigen Prognose vergesellschaftet. Die 5 Jahresmortalität liegt in historischen Arbeiten zwischen 11 und 90%, wobei die Nierenbeteiligung den lebenslimitierenden Faktor darstellt. Der Einfluss einer kombinierten immunsuppressiven Therapie auf den Krankheitsverlauf ist durch die Seltenheit diese Fälle bisher unklar.

Background&Aim: Many patients with penetrating Crohn's disease (CD) undergo surgery for perianal disease of presumed cryptoglandular etiology before diagnosis of IBD is established. This study aimed for the first time (1) to determine the frequency of postoperative IBD diagnosis (Dx-POP) among patients undergoing surgery for perianal abscess or fistula, and (2) to identify predictive factors for Dx-POP.

Hintergrund: Fäkale Mikrobiota Transplantation (FMT) als Therapie einer veränderten Darmflora, auch Dysbiose genannt, ist Gegenstand vieler klinischer Studien als neues therapeutisches Konzept. Der Einsatz wird jedoch aufgrund fehlender Sicherheitsdaten kontrovers diskutiert. Ziel dieser Studie ist es, Kurzzeit- und Langzeitnebenwirkungen sowie Sicherheitsdaten bei immunsupprimierten Patienten darzustellen.

category, respectively.At week 52, remission was achieved by 65 (38%), 42 (37%), and 9 (41%) pts treated with VDZ aged <35, 35 to 55, and >55 years, respectively.AEs occurred at similar rates across the ages (Table ).Three malignancies were reported in VDZtreated pts aged 20 years (carcinoid tumour of the appendix), 45 years (breast cancer), and 52 years (squamous cell carcinoma [skin]).Five deaths were reported: 3 VDZ-treated pts aged <35 years (myocarditis; CD and sepsis; septic shock), 1 VDZ-treated pt aged 46 years (intentional overdose), and 1 PBO-treated pt aged 75 years (bronchopneumonia).Conclusions: These data suggest that the safety and efficacy of VDZ were generally similar in CD pts across all ages.Interpretation of data is limited by the small pt population aged >55 years; these findings should be further evaluated in prospective studies.

Treatment in inflammatory bowel diseases (IBD; Crohn's disease [CD] and ulcerative colitis [UC]) has improved due to biologics. However, a problem is loss of response (LOR) maybe due to the formation of antibodies against these biologics. Our aim was to investigate antibody response against standard biologics infliximab (IFX) and adalimumab (ADA) in adult and paediatric patients with IBD.

Background: As long-term follow-up studies of patients with IBD and anti-TNF treatment are limited we assessed the outcome of our patients.

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.

Hintergrund: Die endoskopische retrograde Cholangiopankreatografie (ERCP) ist mit einem hohen Risiko für Komplikationen behaftet. Einige Risikofaktoren sind bekannt und gut untersucht. Ob der Zeitpunkt der Untersuchung außerhalb der Kernarbeitszeit einen unabhängigen Risikofaktor darstellt, wurde bisher nicht untersucht. Zumeist werden diese akuten Untersuchungen mit gegenüber dem Routinebetrieb eingeschränkten Personalresourcen bei schwer kranken Patienten durchgeführt. Um diese Frage zu klären, wurde im Rahmen des österreichweiten „ERCP Benchmarkings“ im Jahr 2013 erfragt, ob die Untersuchung außerhalb der Kernarbeitszeit erfolgte.