Margarita Elkjaer

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.

Risk of extra-intestinal cancer in inflammatory bowel disease: meta-analysis of population-based cohort studies.

OBJECTIVES:Extra-intestinal manifestations of inflammatory bowel disease (IBD) are relatively common, whereas the risk of extra-intestinal cancer (EIC) remains uncertain. The aim of this study was to obtain a reliable estimate of the risk of EIC in Crohns disease (CD) and ulcerative colitis (UC) by performing a meta-analysis of population-based cohort studies.METHODS:A systematic literature review was performed using MEDLINE (1966–2009) and abstracts from recent international conferences. Eight population-based cohort studies comprising a total of 17,052 patients with IBD were available. Standardized incidence ratios (SIRs) of EICs were pooled in a meta-analysis approach using STATA software.RESULTS:Overall, IBD patients were not at increased risk of EIC (SIR, 1.10; 95% confidence interval (CI) 0.96–1.27). However, site-specific analyses revealed that CD patients had an increased risk of cancer of the upper gastrointestinal tract (SIR 2.87, 95% CI 1.66–4.96), lung (SIR 1.82, 95% CI 1.18–2.81), urinary bladder (SIR 2.03, 95% CI 1.14–3.63), and skin (SIR 2.35, 95% CI 1.43–3.86). Patients with UC had a significantly increased risk of liver–biliary cancer (SIR 2.58, 95% CI 1.58–4.22) and leukemia (SIR 2.00, 95% CI 1.31–3.06) but a decreased risk of pulmonary cancer (SIR 0.39, 95% CI 0.20–0.74).CONCLUSIONS:Although the overall risk of EIC was not significantly increased among patients with IBD, the risk of individual cancer types differed from that of the background population as well as between CD and UC patients. These findings may primarily be explained by smoking habits, extra-intestinal manifestations of IBD, and involvement of the upper gastrointestinal tract in CD.

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.

Overall and cause-specific mortality in Crohn's disease: A meta-analysis of population-based studies

Background: An overview of mortality risk among unselected patients with Crohns disease (CD) is lacking. We therefore performed a systematic review and meta‐analysis of population‐based studies on overall and cause‐specific mortality in CD. Methods: MEDLINE (January 1965 to February 2008), abstracts from international conferences and reference lists of selected articles were searched systematically. All articles fulfilling the predefined inclusion criteria were scrutinized for data on population size, time of follow‐up, gender, age, and observed to expected deaths. STATA meta‐analysis software was used to calculate overall and cause‐specific pooled standardized mortality ratios (SMR, observed/expected). Results: Nine studies were included with overall SMRs ranging from 0.72–3.2, resulting in a significantly increased pooled SMR of 1.39 (95% confidence interval [CI]: 1.30–1.49). Regarding cause‐specific mortality, a significantly increased risk of death from cancer (SMR 1.50, 95% CI: 1.18–1.92), in particular of pulmonary cancer (SMR 2.72, 95% CI: 1.35–5.45), as well as chronic obstructive pulmonary disease (SMR 2.55, 95% CI: 1.19–5.47), gastrointestinal diseases (SMR 6.76, 95% CI: 4.37–10.45), and genitourinary diseases (SMR 3.28, 95% CI: 1.69–6.35) was observed. Conclusions: Among unselected patients with CD, overall mortality was slightly but significantly higher than in the general population—primarily explained by deaths from gastrointestinal, respiratory, and genitourinary diseases. Notably, mortality from colorectal cancer was not increased. Inflamm Bowel Dis 2009

eHealth: individualisation of infliximab treatment and disease course via a self‐managed web‐based solution in Crohn's disease

Infliximab (IFX) maintenance therapy for Crohns disease (CD) is administered every 8 weeks, but inter‐patient variation in optimal treatment intervals may exist.

A new rapid home test for faecal calprotectin in ulcerative colitis

Background  Enzyme‐linked immunosorbent assay (ELISA) is a time‐consuming method for the measurement of faecal calprotectin. Two new quantitative rapid tests have been developed.

Fecal Calprotectin Measured By Patients at Home Using Smartphones—A New Clinical Tool in Monitoring Patients with Inflammatory Bowel Disease

Background:Fecal calprotectin is a reliable noninvasive marker for intestinal inflammation usable for monitoring patients with inflammatory bowel disease. Tests are usually performed by enzyme-linked immunosorbent assay (ELISA), which is time consuming and delays results, thus limiting its use in clinical practice. Our aim was to evaluate CalproSmart, a new rapid test for fecal calprotectin performed by patients themselves at home, and compare it to gold standard ELISA. Methods:A total of 221 patients with inflammatory bowel disease (115 ulcerative colitis and 106 Crohns disease) were included. The CalproSmart test involves extraction of feces, application to the lateral flow device, and taking a picture with a smartphone after 10 minutes of incubation. Results appear on the screen within seconds. Patients were instructed at inclusion and had a video guide of the procedure as support. When using CalproSmart at home, patients also sent in 2 fecal samples to be analyzed by ELISA. Results:Totally, 894 fecal calprotectin results were obtained by ELISA, and 632 of them from CalproSmart. The correlation coefficient was 0.685, higher for academics than nonacademics (0.768 versus 0.637; P = 0.0037). The intra-assay and interassay coefficients of variation of the CalproSmart test were 4.42% and 12.49%, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value were 82%, 85%, 47%, and 97%, respectively, with an optimal cutoff at 150 &mgr;g/g. Conclusions:The CalproSmart test performed by patients with inflammatory bowel disease for fast assessment of gut inflammation seems a reliable alternative to ELISA and presents a new way of monitoring patients by eHealth.

Infliximab dependency in children with Crohn's disease

Background  Recently, infliximab dependency has been described.

Clinical and economic outcomes in a population-based European cohort of 948 ulcerative colitis and Crohn's disease patients by Markov analysis.

Aliment Pharmacol Ther 31, 735–744

5-Aminosalicylic acid dependency in Crohn's disease: A Danish Crohn Colitis Database study

BACKGROUND AND AIMS The role of 5-aminosalicylic acid (5-ASA) in Crohns disease is unclear. The outcome of the first course of 5-ASA monotherapy with emphasis on 5-ASA dependency was retrospectively assessed in consecutive cohort of 537 Crohns disease patients diagnosed 1953-2007. METHODS Following outcome definitions were used: Immediate outcome (30 days after 5-ASA start) defined as complete/partial response (total regression/improvement of symptoms) and no response (no regression of symptoms with a need of corticosteroids, immunomodulator or surgery). Long-term outcome defined as prolonged response (still in complete/partial response 1 year after induction of response); 5-ASA dependency (relapse on stable/reduced dose of 5-ASA requiring dose escalation to regain response or relapse ≤1 year after 5-ASA cessation regaining response after 5-ASA re-introduction). RESULTS One hundred sixty-five (31%) patients had monotherapy with 5-ASA. In 50% 5-ASA monotherapy was initiated ≤1 year after diagnosis (range 0-49 years). Complete/partial response was obtained in 75% and no response in 25% of patients. Thirty-six percent had prolonged response, 23% developed 5-ASA dependency and 38% were non-responders in long-term outcome. Female gender had higher probability to develop prolonged response or 5-ASA dependency (OR 2.89, 95%CI: 1.08-7.75, p=0.04). The median duration (range) of 5-ASA monotherapy was 34 months (1-304) in prolonged responders, 63 (6-336) in 5-ASA dependent and 2 (0-10) in non-responders. CONCLUSIONS A selected phenotype of Crohns disease patients may profit from 5-ASA. Fifty-nine percent of patients obtained long-term benefit with 23% becoming 5-ASA dependent. Prospective studies are warranted to assess the role of 5-ASA in Crohns disease.