Vibeke Wewer

Increasing incidences of inflammatory bowel disease and decreasing surgery rates in Copenhagen City and County, 2003-2005 : A population-based study from the danish crohn colitis database

OBJECTIVES:A continuous increase in the incidence of inflammatory bowel disease (IBD), Crohns disease (CD), ulcerative colitis (UC), and indeterminate colitis (IC) has been suggested. Since Denmark provides excellent conditions for epidemiological research, we aimed to describe contemporary IBD incidence rates and patient characteristics in Copenhagen County and City.METHODS:All patients diagnosed with IBD during 2003–2005 were followed prospectively. Demographic and clinical characteristics, such as disease extent, extraintestinal manifestations, smoking habits, medical treatment, surgical interventions, cancer, and death, were registered.RESULTS:Five-hundred sixty-two patients were diagnosed with IBD, resulting in mean annual incidences of 8.6/105 for CD, 13.4/105 for UC, and 1.1/105 for IC. Time from onset to diagnosis was 8.3 months in CD and 4.5 months in UC patients. A family history of IBD, smoking, and extraintestinal manifestations was significantly more common in CD than in UC patients. Only 0.6% of UC patients had primary sclerosing cholangitis. In CD, old age at diagnosis was related to pure colonic disease, whereas children significantly more often had proximal and extensive involvement. Twelve percent of CD patients and 6% of UC patients underwent surgery during the year of diagnosis, significantly less than earlier reported.CONCLUSIONS:The incidence of IBD in Copenhagen increased noticeably during the last decades. Time from onset of symptoms until diagnosis decreased markedly, extent of CD was related to age at diagnosis, and the risk of surgery was low in UC.

Infliximab for Inflammatory Bowel Disease in Denmark 1999–2005: Clinical Outcome and Follow-Up Evaluation of Malignancy and Mortality

BACKGROUND & AIMS Data on safety and long-term follow-up evaluation of population-based cohorts of inflammatory bowel disease (IBD) patients treated with infliximab are sparse. The aim of this article is to describe the use of infliximab in a national Danish population-based IBD cohort during 1999-2005. METHODS Medical records of all infliximab-treated IBD patients were scrutinized to abstract information on patient demographics, treatment efficacy, and adverse events. RESULTS A total of 651 patients (619 with Crohns disease, 15 with ulcerative colitis, and 17 with colonic IBD type unclassified) received infliximab during 1999-2005. A total of 3351 infusions were administered, with a median of 3 infusions per patient. A positive clinical response was observed in 82.7% (95% confidence interval, 79.9-85.5) of patients. Infusion reactions were observed after 146 of 3351 infusions (4.4%). Significantly fewer infusion reactions were seen in patients also receiving azathioprine or methotrexate (63 of 2079; 3.0%), compared with patients not receiving azathioprine or methotrexate (83 of 1272; 6.5%) (P < .0001). Severe adverse events were observed after 112 of 3351 infusions (3.3%) in a total of 95 patients (14.6%). Four patients developed cancer versus 5.9 expected (standardized incidence ratio, 0.7; 95 confidence interval, 0.2-1.7) and 13 patients died versus 6.9 expected (standardized mortality ratio, 1.9; 95% confidence interval, 1.0-3.2). Two deaths caused by infections were possibly related to infliximab. CONCLUSIONS Infliximab seemed effective in IBD and generally was well tolerated. However, rare but severe adverse events occurred, and patients receiving infliximab therefore should be selected carefully and monitored closely. No lymphomas and no increased risk of cancer were observed.

Pediatric inflammatory bowel disease: increasing incidence, decreasing surgery rate, and compromised nutritional status: A prospective population-based cohort study 2007-2009.

Background: The aim was to evaluate the incidence, treatment, surgery rate, and anthropometry at diagnosis of children with inflammatory bowel disease (IBD). Methods: Patients diagnosed between January 1, 2007 to December 31, 2009 in Eastern Denmark, Funen, and Aarhus were included from a background population of 668,056 children <15 years of age. For evaluation of incidence, treatment, and surgery rate, a subcohort from Eastern Denmark was extracted for comparison with a previously published population‐based cohort from the same geographical area (1998–2006). Results: In all, 130 children with IBD: 65 with Crohns disease (CD), 62 with ulcerative colitis (UC), and three with IBD unclassified (IBDU) were included. The mean incidence rates per 106 in 2007–2009 were: IBD: 6.4 (95% confidence interval [CI]: 5.4–7.7), CD: 3.2 (2.5–4.1), UC: 3.1 (2.4–4.0) and IBDU: 0.2 (0.05–0.5). Comparing the two cohorts from Eastern Denmark we found higher incidence rates for IBD (5.0 and 7.2 in 1998–2000 and 2007–2009, respectively, P = 0.02) and CD (2.3 versus 3.3, P = 0.04). Furthermore, we found a significant decrease in surgery rates (15.8/100 person‐years versus 4.2, P = 0.02) and an increase in the rate of initiating immunomodulators (IM) within the first year (29.0/100 person‐years versus 69.2, P < 0.001). IM use was associated with a trend towards a decreased surgery risk (relative risk [RR] 0.38; 0.15–1.0). Children with CD had poor nutritional status at diagnosis compared with the general pediatric population. Conclusions: Over the past 12 years we found an increase in the incidence of IBD in children, an increasing use of IM, and decreasing 1‐year surgery rates. CD patients had poor nutritional status.

Infliximab dependency in a national cohort of children with Crohn's disease.

Aim: The aim was to evaluate the pattern of responsiveness and to monitor side effects of episodic administration of infliximab in children with active Crohns disease (CD) treated in Denmark from 1999 to 2003. Material and Methods: The National Danish Crohn Colitis Database of infliximab was used to identify all Danish CD patients treated at pediatric departments with infliximab. The clinical outcome was assessed by pattern recognition of the disease course 30 days after the first infliximab infusion and 90 days after intended end of treatment. Results: During a 3 year period, infliximab was given to 24 CD patients (9 male/15 female) aged median 15.4 (range 9.8-18.6) years with a median disease duration of 26 (range 0.7-93) months and a median number of infusions of 6 (range 2-11). Five milligrams of infliximab per kilogram infusions were given intravenously. Immediate response was as follows: 8 (33%) patients achieved complete response (CR), 10 (42%) partial response (PR), and 6 (25%) no response (NR). Long-term response was as follows: 7 (29%) patients achieved prolonged response (PRO), defined as maintenance of CR or PR, 10 (42%) were infliximab dependent (ID), defined as relapse of symptoms requiring reinfusions of infliximab to regain CR or PR, and 6 (25%) had NR. Six (25%) patients needed surgery during or after treatment with infliximab. Side effects were seen in four (17%) patients. No serious events were noted. Conclusion: Seventy-one percent of the children appeared to benefit (PRO or ID) from infliximab treatment with minor side effects when given episodically. Among these patients, two response patterns were recognized: PRO after ending infliximab treatment (29%) or dependency on reinfusions of infliximab (42%).

Differences in phenotype and disease course in adult and paediatric inflammatory bowel disease – a population-based study

Aliment Pharmacol Ther 2011; 34: 1217–1224

Prevalence of hepatobiliary dysfunction in a regional group of patients with chronic inflammatory bowel disease.

A regional group of outpatients with chronic inflammatory bowel disease (ulcerative colitis, n = 396, and Crohns disease, n = 125) was biochemically screened to estimate the prevalence of hepatobiliary dysfunction. Among the 396 patients with ulcerative colitis, 69 (17%; 95% confidence limits, 14-22%) had at least 1 abnormal laboratory value. Serum bilirubin was elevated in 5%, alkaline phosphatases in 8%, aspartate aminotransferases in 4%, and alanine aminotransferases in 8% of the patients. Two per cent had decreased plasma coagulation factors (2.7 and 10) and serum albumin. Further diagnositc evaluation consisting of ultrasonography, liver biopsy, and endoscopic retrograde cholangiography was performed in patients who had biochemical values more than twice the upper normal limit in two consecutive blood tests within a fortnight. Six patients (1%) fulfilled this criterion. Three patients had primary sclerosing cholangitis, of whom two were primarily diagnosed; one patient had cholangiocarcinoma also primarily diagnosed; and two patients were found to have alcoholic hepatic damage. Among the 125 patients with Crohns disease, 38 (30%; 95% confidence limits, 23-38%) had at least 1 abnormal laboratory value. Serum bilirubin was elevated in 2%, alkaline phosphatases in 18%, asparetate aminotransferases in 3%, and alanine aminotransferases in 10% of the patients. One per cent had decreased plasma coagulation factors (2.7 and 10) and serum albumin concentrations. Three patients (2%) fulfilled the criteria for further evaluation as described above. One patient appeared to have epithelioid granuloma in the liver and one patient had alcoholic liver disease, whereas one patient refused further examination.(ABSTRACT TRUNCATED AT 250 WORDS)

J-pouch ileoanal anastomosis in children and adolescents with ulcerative colitis: functional outcome, satisfaction and impact on social life.

Objectives: The aim of this study was to evaluate, over a 10-year period, severe surgical complications, functional outcome, patient satisfaction and impact on social life after colectomy and J-pouch ileoanal anastomosis for children and adolescents <18 years with ulcerative colitis. Methods: Data were extracted retrospectively from medical records and obtained by mailed questionnaire. Results: Thirty patients (18 girls) with a median age of 15 years (range, 7-17 years) were identified. Two patients (7%) had the J-pouch removed because of intractable diarrhea. Twenty-seven of 28 patients with preserved J-pouch answered the questionnaire. The median follow-up was 3.7 years (range, 0.3-9.2 years). Surgical complications included eight of 30 patients (27%) with small bowel obstruction, one of 30 (4%) with intra-abdominal abscess and two of 30 (7%) with perforation of the small intestine. The median number of daytime bowel movements was six (range, 3-10) and the median number of nighttime bowel movements was one (range, 0-2). Twelve patients (44%) were completely continent for stool and mucus, 12 patients (44%) leaked now and then and three (12%) leaked often or always. Antibiotic treatment for pouchitis was given in 13 patients (48%). Seventeen patients (63%) were completely satisfied with the operation, nine patients (33%) found the result fairly good and one patient (4%) was not satisfied. Twenty-six patients (96%) reported their health as completely or fairly good. Conclusions: The majority of patients with an intact J-pouch had an acceptable functional result with respect to defecation frequency, continence and number of pouchitis episodes. Most patients reported being satisfied with the procedure.

Paediatric inflammatory bowel disease during a 44-year period in Copenhagen County: occurrence, course and prognosis--a population-based study from the Danish Crohn Colitis Database.

Aim To describe the development in incidence, disease localization, activity, surgery and prognosis in two Danish paediatric population-based inflammatory bowel disease (IBD) cohorts comparing the time periods 1962–1987 (period I) and 1998–2006 (period II). Materials and methods Incident IBD patients below 15 years of age were included. Disease localization was classified according to the Montreal classification for ulcerative colitis (UC) patients and into small bowel, large bowel and small and large bowel combined for Crohns disease (CD) patients. Disease activity and surgery in the first 2 years after diagnosis were assessed. Standardized cancer incidence rates and standardized mortality rates were calculated. Results One hundred and nineteen IBD patients (77 UC and 42 CD) were included. Comparing periods II and I, the incidence rate ratios were 0.81 [95% confidence interval (CI): 0.5–1.4] and 15.6 (95% CI: 7.5–32.7) in UC and CD, respectively. The number of UC patients with extensive disease (E3) increased from period I to II (46.7 vs. 94.1%, P<0.001). No colectomies were performed in UC patients in period II compared with nine in period I (P = 0.13) within the first 2 years after diagnosis. For patients diagnosed in period I, the standardized cancer incidence rate for UC was 37.9 (95% CI: 4.6–136.7) after a median follow-up period of 26 years. Conclusion We found a significant 15-fold increase in the incidence of CD and a significant increase in the number of UC patients with extensive disease in period II compared with period I. After a median follow-up time of 26 years, a possible increased risk of colorectal cancer in UC patients was detected.

Frequency and risk factors of gastric and duodenal ulcers or erosions in children: a prospective 1-month European multicenter study

There are no solid figures of the frequency of ulcer disease during childhood in Europe. We assessed its frequency and analyzed known risk factors. Patients and methods Ulcers, erosions, indications, and risk factors were recorded in all children undergoing an upper gastrointestinal endoscopy in a prospective study carried out during 1-month simultaneously in 19 centers among 14 European countries. Results Ulcers and/or erosions were observed in 56 out of 694 children. Children with ulcers/erosions were significantly older than those without lesions (10.3±5.5 vs. 8.1±5.7 years, P=0.002). Helicobacter pylori infection was present in 15 of 56 children (27%) where NSAIDs were used in eight, steroids in five, immune-suppressive drugs in five, antibiotics in six, antacids in one, H2-blockers in six and proton pump inhibitors in eight children (more than one risk factor was detected in 32 of 56 children). No risk factors were observed in 24 of 56 children (43%). The main indications for endoscopy were epigastric or abdominal pain (24%) and suspicion of gastroesophageal reflux disease (15%). Similarly, epigastric tenderness, hematemesis, melena, and weight stagnation were significantly associated with ulcers/erosions, whereas sex, H. pylori infection, socioeconomic and lifestyle factors were equally distributed. Conclusion Although limited by the short-time duration and the heterogeneity of the patients included throughout the 19 centers, our study shows a frequency of 8.1% of ulcers and/or erosions in children, occurring mainly in the second decade of life. H. pylori infection and gastrotoxic medications were less frequently implicated than expected.

Steroid dependency and pediatric inflammatory bowel disease in the era of immunomodulators—A population‐based study

Background: The aim was to investigate the impact of systemic steroid treatment (SST) and immunomodulators (IM) on disease course in children with inflammatory bowel disease (IBD). Methods: All IBD patients in eastern Denmark <15 years of age diagnosed in the period 1998–2006 starting their first SST within 2 years of diagnosis were included. Results: In all, 205 IBD patients were included (105 Crohns disease [CD], 100 ulcerative colitis [UC]). Eighty‐seven CD (83%) and 77 (77%) UC patients started SST. In CD, 55 (63%), 25 (29%), and 7 (8%) had a complete response (CR), partial response (PR), or no response (NR), respectively, 30 days after initiation of SST. Fifty (58%) had a prolonged response (PRO) and 32 (37%) were steroid‐dependent (SD). In UC, 49 (64%), 22 (28%), and 6 (8%) had CR, PR, and NR, respectively, and 38 (49%) and 38 (49%) were PRO and SD. The cumulative risk of surgery 1 year after starting SST was 11.5% and 7.8% for CD and UC patients, respectively. After a median follow‐up period of 5.1 years, no difference in the risk of surgery or periods of activity and remission was found between PRO and SD in CD or UC. IM use was associated with a milder disease course in UC patients. Conclusions: No difference in surgery rates or disease course was found between SD and PRO. Surgery rates were lower than rates from studies predating the era of IM, indicating a putative effect of IM on disease course. (Inflamm Bowel Dis 2010;)