B. Bokemeyer

Second European evidence-based consensus on the diagnosis and management of ulcerative colitis part 3: special situations.

### 8.1 General Proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the procedure of choice for most patients with ulcerative colitis (UC) requiring colectomy.1 Pouchitis is a non-specific inflammation of the ileal reservoir and the most common complication of IPAA in patients with UC.2–7 Its frequency is related to the duration of follow up, occurring in up to 50% of patients 10 years after IPAA in large series from major referral centres.1–9 The cumulative incidence of pouchitis in patients with an IPAA for familial adenomatous polyposis is much lower, ranging from 0 to 10%.10–12 Reasons for the higher frequency of pouchitis in UC remain unknown. Whether pouchitis more commonly develops within the first years after IPAA or whether the risk continues to increase with longer follow up remains undefined. ### Statement 8A The diagnosis of pouchitis requires the presence of symptoms, together with characteristic endoscopic and histological abnormalities [EL3a, RG B]. Extensive UC, extraintestinal manifestations (i.e. PSC), being a non-smoker, p-ANCA positive serology and NSAID use are possible risk factors for pouchitis [EL3b, RG D] #### 8.1.1 Symptoms After proctocolectomy with IPAA, median stool frequency is 4 to 8 bowel movements,1–4,13,14 with about 700 mL of semiformed/liquid stool per day,2,13,14 compared to a volume of 200 mL/day in healthy people. Symptoms related to pouchitis include increased stool frequency and liquidity, abdominal cramping, urgency, tenesmus and pelvic discomfort.2,15 Rectal bleeding, fever, or extraintestinal manifestations may occur. Rectal bleeding is more often related to inflammation of the rectal cuff (“cuffitis,” Section 1.4),16 than to pouchitis. Faecal incontinence may occur in the absence of pouchitis after IPAA, but is more common in patients with pouchitis. Symptoms of pouch dysfunction in patients with IPAA may be caused by conditions other than pouchitis, including Crohns disease of the pouch,17–19 cuffitis16 and an irritable pouch …

FERGIcor, a Randomized Controlled Trial on Ferric Carboxymaltose for Iron Deficiency Anemia in Inflammatory Bowel Disease

BACKGROUND & AIMS Iron deficiency anemia (IDA) is common in chronic diseases and intravenous iron is an effective and recommended treatment. However, dose calculations and inconvenient administration may affect compliance and efficacy. We compared the efficacy and safety of a novel fixed-dose ferric carboxymaltose regimen (FCM) with individually calculated iron sucrose (IS) doses in patients with inflammatory bowel disease (IBD) and IDA. METHODS This randomized, controlled, open-label, multicenter study included 485 patients with IDA (ferritin <100 μg/L, hemoglobin [Hb] 7-12 g/dL [female] or 7-13 g/dL [male]) and mild-to-moderate or quiescent IBD at 88 hospitals and clinics in 14 countries. Patients received either FCM in a maximum of 3 infusions of 1000 or 500 mg iron, or Ganzoni-calculated IS dosages in up to 11 infusions of 200 mg iron. Primary end point was Hb response (Hb increase ≥ 2 g/dL); secondary end points included anemia resolution and iron status normalization by week 12. RESULTS The results of 240 FCM-treated and 235 IS-treated patients were analyzed. More patients with FCM than IS achieved Hb response (150 [65.8%] vs 118 [53.6%]; 12.2% difference, P = .004) or Hb normalization (166 [72.8%] vs 136 [61.8%]; 11.0% difference, P = .015). Both treatments improved quality of life scores by week 12. Study drugs were well tolerated and drug-related adverse events were in line with drug-specific clinical experience. Deviations from scheduled total iron dosages were more frequent in the IS group. CONCLUSIONS The simpler FCM-based dosing regimen showed better efficacy and compliance, as well as a good safety profile, compared with the Ganzoni-calculated IS dose regimen.

Updated German Guideline on Diagnosis and Treatment of Ulcerative Colitis, 2011

! Hintergrund Die Colitis ulcerosa (CU) ist neben dem Morbus Crohn die wichtigste chronisch-entzundliche Darmerkrankung (CED). Die Inzidenz fur die Colitis ulcerosa liegt in Deutschland bei bei 3,0–3,9 pro 100000 Einwohner [1, 2]. Die Pravalenz durfte in der westlichen Welt derzeit bei 160– 250 pro 100000 Einwohner liegen [3, 4]. Der hochste Gipfel der alterspezifischen Inzidenz liegt bei den 16bis 25-Jahrigen, wenn auch die Verteilung uber die Altersdekaden weit gleichmasiger ist als fruher beschrieben wurde [2]. Somit beginnt fur die meisten Patienten ihre Erkrankung wahrend der Schulzeit oder der Berufausbildung und dauert wahrend ihres gesamten beruflichen Lebens an. Daraus folgt, dass durch die Erkrankung nicht nur direkte Kosten (Medikamente, Arztbesuche, Operationen, Krankenhausaufenthalte etc.), sondern auch umfangreiche indirekte Kosten (Rente, Arbeitsausfalle etc.) entstehen. Es ist davon auszugehen, dass bei Patienten mit CU ca. die Halfte der Gesamtkosten den indirekten Kosten zuzuordnen sind [5]. An direkten medizinischen Kosten wurden dabei zuletzt zwischen 2500 und 5000€ pro Inhaltsverzeichnis! Hintergrund Die Colitis ulcerosa (CU) ist neben dem Morbus Crohn die wichtigste chronisch-entzündliche Darmerkrankung (CED). Die Inzidenz für die Colitis ulcerosa liegt in Deutschland bei bei 3,0–3,9 pro 100000 Einwohner [1, 2]. Die Prävalenz dürfte in der westlichen Welt derzeit bei 160– 250 pro 100000 Einwohner liegen [3, 4]. Der höchste Gipfel der alterspezifischen Inzidenz liegt bei den 16bis 25-Jährigen, wenn auch die Verteilung über die Altersdekaden weit gleichmäßiger ist als früher beschrieben wurde [2]. Somit beginnt für die meisten Patienten ihre Erkrankung während der Schulzeit oder der Berufausbildung und dauert während ihres gesamten beruflichen Lebens an. Daraus folgt, dass durch die Erkrankung nicht nur direkte Kosten (Medikamente, Arztbesuche, Operationen, Krankenhausaufenthalte etc.), sondern auch umfangreiche indirekte Kosten (Rente, Arbeitsausfälle etc.) entstehen. Es ist davon auszugehen, dass bei Patienten mit CU ca. die Hälfte der Gesamtkosten den indirekten Kosten zuzuordnen sind [5]. An direkten medizinischen Kosten wurden dabei zuletzt zwischen 2500 und 5000€ pro Inhaltsverzeichnis

Randomized, Double Blind Controlled Trial of Subcutaneous Recombinant Human Interleukin-11 Versus Prednisolone in Active Crohn's Disease

BACKGROUND: Interleukin-11 has shown benefit in animal inflammatory bowel disease models. Recently, recombinant human interleukin-11 (rhIL-11) has been observed to induce remission in a subset of patients with mild to moderate Crohns disease (CD). The present study compared the efficacy of rhIL-11 versus prednisolone in remission induction in CD.METHODS: Patients with active CD were randomly assigned to receive either subcutaneous rhIL-11 (1 mg once weekly) and prednisolone placebo tablets, or active prednisolone (60 mg/day) and rhIL-11 placebo, for 12 weeks. Prednisolone/placebo was tapered after week 1, and patients were assessed every second week.RESULTS: Fifty-one patients received medication: 13/27 (rhIL-11) and 17/24 (prednisolone) completed 12 weeks of treatment. Remission rates (intent to treat) for rhIL-11 versus prednisolone were 4%versus 46% at week 4 (p < 0.001) and 19%versus 50% at week 6 (p < 0.05). Response to treatment (ΔCDAI > 100) was seen in 19% (rhIL-11) versus 63% (prednisolone) after 4 weeks (p < 0.002) and 37%versus 63% after 6 weeks (p= 0.1). After 12 weeks of treatment, it was observed that 22% (rhIL-11) versus 21% (prednisolone) had remained in remission. Frequent side effects of rhIL-11 included fever (n = 3), rash (4), arthralgia/arthritis (3), nausea/vomiting (3), and headache (6).CONCLUSION: rhIL-11 is well tolerated but significantly inferior when compared to prednisolone in short-term remission induction in patients with active CD. In this patient cohort, both treatments appeared to be poor in maintaining remission over a period of 3 months.

Vedolizumab induction therapy for inflammatory bowel disease in clinical practice – a nationwide consecutive German cohort study

Vedolizumab (VDZ) is a humanised monoclonal IgG1 antibody targeting α4β7 integrin.

Ferric Carboxymaltose Prevents Recurrence of Anemia in Patients With Inflammatory Bowel Disease

BACKGROUND & AIMS Iron-deficiency anemia is the most common systemic complication of inflammatory bowel diseases (IBD). Iron-deficiency anemia recurs frequently and rapidly after iron-replacement therapy in patients with IBD. We performed a randomized, placebo-controlled trial to determine if administration of ferric carboxymaltose (FCM) prevents anemia in patients with IBD and low levels of serum ferritin. METHODS We performed a single-blind, multicenter study of nonanemic patients who had completed the FERGIcor study. Serum levels of ferritin were assessed every second month, and patients were given FCM (total iron dose, 1181 ± 662 mg; n = 105) or placebo (n = 99) when levels decreased to less than 100 μg/L. The primary end point was time to recurrence of anemia within 8 months. Secondary end points included changes of quality of life, disease activity, results from laboratory tests, and adverse events. RESULTS Anemia recurred in 26.7% of subjects given FCM and in 39.4% given placebo. The time to anemia recurrence was longer in the FCM group (hazard ratio, 0.62; 95% confidence interval, 0.38-1.00; P = .049). Markers of body levels of iron increased or remained at normal levels in subjects given FCM (ferritin increased by 30.3 μg/L, transferrin saturation increased by 0.6%) but decreased in the group given placebo (ferritin decreased by 36.1 μg/L, transferrin saturation decreased by 4.0%). Changes in quality of life and disease activity were comparable between groups. Adverse events were reported in 59.0% of the FCM group and 50.5% of the placebo group, and serious adverse events were reported in 6.7% and 8.1%, respectively. CONCLUSIONS FCM prevents recurrence of anemia in patients with IBD, compared with placebo. Nevertheless, the high rate of anemia recurrence warrants optimization of the frequency and requirements for FCM treatment.

Adherence to thiopurine treatment in out-patients with Crohn’s disease

Background  High frequency of incomplete or non‐response to azathioprine (AZA) and/or mercaptopurine (MP) limit their use in Crohn’s disease (CD). Non‐adherence is considered to be of relevance for ineffectiveness.

Non-colorectal intestinal tract carcinomas in inflammatory bowel disease: results of the 3rd ECCO Pathogenesis Scientific Workshop (II)

Patients with inflammatory bowel diseases (IBD) have an excess risk of certain gastrointestinal cancers. Much work has focused on colon cancer in IBD patients, but comparatively less is known about other more rare cancers. The European Crohns and Colitis Organization established a pathogenesis workshop to review what is known about these cancers and formulate proposals for future studies to address the most important knowledge gaps. This article reviews the current state of knowledge about small bowel adenocarcinoma, ileo-anal pouch and rectal cuff cancer, and anal/perianal fistula cancers in IBD patients.

Screening colonoscopy for colorectal cancer prevention: results from a German online registry on 269 000 cases

Background The efficacy of screening colonoscopy in general use remains to be determined. Here we report data over a 39-month study period collected in a nationwide online registry. Study Data from consecutive screening colonoscopies performed on asymptomatic patients in the practices of 280 participating gastroenterologists (age 55–99 years) were collected in an online registry. The number and histology of colorectal polyps and carcinomas, complication rates of colonoscopy and polypectomy were registered. Advanced adenoma was defined as an adenoma of ≥10 mm in diameter, villous or tubulovillous in histology, or presence of high-grade dysplasia. Results A total of 269 144 colonoscopies (male 44%) were evaluated. Tubular, villous/tubulovillous adenomas and invasive cancers were found in 15.6, 3.7, and 0.8%, respectively. Advanced adenomas amounted to 7.1%. In 95% of polyps greater than 5 mm and less than 30 mm immediate polypectomy was performed. In 399 of the 575 carcinomas with complete tumor node metastasis stages, which were detected during colonoscopy, early stages dominated (UICC stages I and II in 43 and 27%, respectively). Complication rate was low and no fatalities were observed: cardiopulmonary complication in 0.10% of the colonoscopies, bleeding in 0.8% of polypectomies most of which were managed endoscopically (surgery in 0.03% of polypectomies). Perforation occurred in 0.02% of the colonoscopies and 0.09% of polypectomies. Conclusion Colonic neoplasias are detected in about 20% of patients most of which are immediately removed by polypectomy at a low risk. Polypectomy of adenomas and low UICC stages in cancer patients during screening colonoscopy may be tools for fighting colorectal cancer mortality.

Epidemiologie der chronischen Hepatitis C in Deutschland - Eine Analyse von 10 326 Hepatitis-C-Virus-Infizierten aus Schwerpunktpraxen und -ambulanzen

Little is known about the epidemiology of chronic hepatitis C (CHC) in Germany and especially about the importance of transmission, duration of infection, genotypes, symptoms and quality of life of the patients. The current study prospectively evaluates epidemiological and clinical data of patients infected with the hepatitis C virus (HCV). Using online data entry, various characteristics of 10,326 untreated patients with CHC were documented from March 2003 until May 2006 in 352 centres all over Germany. Mean age of patients was 43.4 years. Patients infected by i.v. drug abuse were considerably younger (36.5 years) than the remaining patients (49.2 years). As indicated by their native language, 64.4% of the patients came from Germany and 19.2% from Russia. 61.7% were infected with genotype 1 and 34.9% with genotype 2 or 3. 45.5% of the patients had been infected by i.v. drug abuse. In at least 5.4% of the patients liver cirrhosis had been proved by biopsy. 63.5% of the patients felt an impairment of quality of life caused by CHC. In many patients infected with hepatitis C socio-economic issues are existent. This is reflected, i.e., in very high rates of unemployment in special subpopulations. Coinfections with hepatitis B and HIV occurred in 1.5% and 4.7%, respectively. Nearly 80% of patients were managed near their homes. The data of the 10 326 patients represent about 2% of all German patients with CHC. This database is up to now the largest of its kind and gives a representative insight into the epidemiological situation of CHC in Germany.