Premedication with corticosteroids does not impact the pharmacokinetics of infliximab in inflammatory bowel disease irrespective of azathioprine cotreatment.

OBJECTIVE: Loss of infliximab (IFX) effect is a clinical challenge in the management of patients with Crohn's disease (CD), but this can potentially be reduced with azathioprine (AZA) or with corticosteroids (CS). We aimed to study whether CS premedication with or without cotreatment with AZA could reduce antibody formation and affect the IFX elimination rate. PATIENTS AND METHODS: A cross-sectional observational study was conducted at two centers with CD patients receiving maintenance IFX therapy for 12-18 months. In addition to IFX, patients received either CS premedication or not, with or without concominant AZA. RESULTS: Fifty-seven patients were included in the study. Thirty-one patients received premedication with CSs, and 11 (35.5%) of these also received AZA, whereas this was the case for 22 of 26 (84.6%) patients in the non-CS group. No difference in IFX trough level (P=0.10) or halftime elimination (P=0.31) was observed with or without CS premedication. Concomitant AZA was associated with significantly longer mean half-life of IFX (P=0.04). Total IFX antibody concentrations were 15.8 and 12.9 with and without CS, respectively, in those not receiving AZA versus 4.3 and 6.1 AU/ml with and without CS, respectively, in those receiving AZA (P=0.004). Premedication with CS did not have any effect on the frequency of antibody formation (P=0.28). CONCLUSION: In patients with CD and in maintenance IFX therapy, premedication with CS did not influence antibody formation, IFX trough levels or IFX halftime elimination, irrespective of concomitant AZA use. However, the use of AZA was associated with higher IFX trough levels and lower total IFX antibody concentrations.

A cross-continental analysis of weight gain, psychiatric diagnoses and medication use during inpatient psychiatric treatment. The international study on physical illness in mentally ill.

Weight gain among psychiatric inpatients is a widespread phenomenon. This change in body mass index (BMI) can be caused by several factors. Based on recent research, we assume the following factors are related to weight gain during psychiatric inpatient treatment: psychiatric medication, psychiatric diagnosis, sex, age, weight on admission and geographic region of treatment. 876 of originally recruited 2328 patients met the criteria for our analysis. Patients were recruited and examined in mental health care centres in Nigeria (N = 265), Japan (N = 145) and Western-Europe (Denmark, Germany and Switzerland; N = 466). There was a significant effect of psychiatric medication, psychiatric diagnoses and geographic region, but not age and sex, on BMI changes. Geographic region had a significant effect on BMI change, with Nigerian patients gaining significantly more weight than Japanese and Western European patients. Moreover, geographic region influenced the type of psychiatric medication prescribed and the psychiatric diagnoses. The diagnoses and psychiatric medication prescribed had a significant effect on BMI change. In conclusion, we consider weight gain as a multifactorial phenomenon that is influenced by several factors. One can discuss a number of explanations for our findings, such as different clinical practices in the geographical regions (prescribing or admission strategies and access-to-care aspects), as well as socio-economic and cultural differences.

High-dose fast infusion of parenteral iron isomaltoside is efficacious in inflammatory bowel disease patients with iron-deficiency anaemia without profound changes in phosphate or fibroblast growth factor 23.

OBJECTIVE: Iron isomaltoside (Monofer(®)) is a high-dose intravenous iron preparation with good tolerability and efficacy in inflammatory bowel disease (IBD) patients with iron deficiency anaemia (IDA). This trial evaluates the safety and efficacy, including effect on intact fibroblast growth factor 23 (iFGF23) of a high single dose and cumulative doses of iron isomaltoside in IBD patients with IDA. MATERIALS AND METHODS: The trial was a prospective, open-label, multi-centre trial conducted in IBD patients with IDA. Based upon haemoglobin (Hb) levels at baseline and weight, the patients received 1500, 2000, 2500 or 3000 mg of iron isomaltoside infused in single doses up to 2000 mg. The outcome measurements included adverse drug reactions (ADRs) and changes in haematology and biochemistry parameters. RESULTS: Twenty-one IBD patients with IDA were enrolled, receiving 1500 (seven patients), 2000 (eight patients), 2500 mg (four patients) or 3000 (two patients) mg of iron. No serious ADRs were observed. Four patients experienced nine mild to moderate ADRs (hypersensitivity, pyrexia, vomiting, constipation, abdominal pain, dyspepsia (two events) and eye allergy (two events)). In total, 15 (75%) patients had an increase in Hb of ≥2.0 g/dL during the trial, with normalisation of ferritin. No changes in iFGF23 or clinically significant hypophosphataemia were found. CONCLUSION: Rapid infusions of high-dose iron isomaltoside, administered as single doses up to 2000 mg and cumulative doses up to 3000 mg, were without safety concerns and were efficacious in increasing Hb levels in IBD patients. Iron isomaltoside did not induce profound phosphate wasting via increased iFGF23 levels.

Individualized Therapy Is a Long-Term Cost-Effective Method Compared to Dose Intensification in Crohn's Disease Patients Failing Infliximab.

BACKGROUND: In Crohn's disease patients failing infliximab therapy, interventions defined by an algorithm based on infliximab and anti-infliximab antibody measurements have proven more cost-effective than intensifying the infliximab regimen. AIM: This study investigated long-term economic outcomes at the week 20 follow-up study visit and after 1 year. Clinical outcomes were assessed at week 20. METHODS: Follow-up from a 12-week, single-blind, clinical trial where patients with infliximab treatment failure were randomized to infliximab intensification (5 mg/kg every 4 weeks) (n = 36), or algorithm-defined interventions (n = 33). Accumulated costs, expressed as mean costs per patient, were based on the Danish National Patient Registry. RESULTS: At the scheduled week 20 follow-up study visit, response and remission rates were similar in all study subpopulations between patients treated by the algorithm or by infliximab intensification. However, the sum of healthcare costs related to Crohn's disease was substantially lower (31 %) for patients randomized to algorithm-based interventions than infliximab intensification in the intention-to-treat population: $11,940 versus $17,236; p = 0.005. For per-protocol patients (n = 55), costs at the week 20 follow-up visit were even lower (49 %) in the algorithm group: $8,742 versus $17,236; p = 0.002. Figures were similar for patients having completed the 12-week trial as per protocol (50 % reduction in costs) (n = 45). Among patients continuing the allocated study intervention throughout the entire 20-week follow-up period (n = 29), costs were reduced by 60 % in algorithm-treated patients: $7,056 versus $17,776; p < 0.001. Cost-reduction percentages remained stable throughout one year. CONCLUSION: Economic benefit of algorithm-based interventions at infliximab failure is maintained throughout 1 year.

Cancer risk in inflammatory bowel disease according to patient phenotype and treatment: a Danish population-based cohort study.

OBJECTIVES: Population-based studies of site-specific cancer risk in patients with inflammatory bowel disease (IBD) according to IBD phenotype and treatment are lacking. We studied cancer risk in a well-characterized population-based IBD cohort from North Jutland County, Denmark. METHODS: A total of 1,515 patients were diagnosed with ulcerative colitis (UC) and 810 with Crohn's disease (CD) during 1978-2002. Patients were followed until 31 December 2010 for occurrence of incident cancer, identified in the Danish Cancer Registry. Observed numbers of cancer were compared with expected numbers (based on age- and sex-specific background rates) and presented as standardized incidence ratios (SIRs) with 95% confidence intervals (CIs). RESULTS: Patients with UC were not at increased risk of cancer overall (SIR, 1.12; 95% CI, 0.97-1.28) despite increased risk of prostate cancer (SIR, 1.82; 95% CI, 1.17-2.71). Patients with CD had a 55% increased risk of cancer overall (SIR, 1.55; 95% CI, 1.29-1.84) related to young age, colonic disease, smoking, and thiopurine exposure. Patients were at increased risk of small bowel cancer (SIR, 15.18; 95% CI, 1.84-54.78), lung cancer (SIR, 2.13; 95% CI, 1.19-3.52 (associated with female gender and smoking)), colorectal cancer in males (SIR, 2.43; 95% CI, 1.05-4.78), cervical dysplasia (SIR, 1.65; 95% CI, 1.10-2.37 (associated with young age at diagnosis, smoking, 5-aminosalicylic acid, and thiopurine exposure)), and non-Hodgkin lymphoma (SIR, 3.43; 95% CI, 1.38-7.07 (unrelated to thiopurine exposure)). CONCLUSIONS: Patients with CD, but not UC, have an overall excess risk of cancer. Clinical characteristics of IBD patients at excess risk differ by cancer subtype.

Cultural diversity in physical diseases among patients with mental illnesses.

OBJECTIVE: People with psychiatric diseases have a severely increased risk for physical morbidity and premature death from physical diseases. The aims of the study were to investigate the occurrence of cardiovascular diseases (CVD), diabetes (DM) and obesity in schizophrenia and depression in three different geographical areas - Asia (Japan), Africa (Nigeria) and Western Europe (Switzerland, Germany and Denmark) - and to search for possible transcultural differences in these correlations, which would also reflect the differences between low-income areas in Africa (Nigeria) and high-income areas in Europe and Japan. METHOD: Patients with International Classification of Diseases (ICD-10) F2 diseases (schizophrenia spectrum disorders) and F3 diseases (affective disorders) admitted to one Nigerian, one Japanese, two Swiss, two German and six Danish centres during 1 year were included. Physical diseases in accordance with ICD-10 were also registered. Psychiatric and physical comorbidity were calculated and standardized rate ratio incidences of background populations were our primary measures. RESULTS: Incidence rate ratios were increased for both CVD, DM and overweight in both F2 and F3 in all cultures (Western Europe, Nigeria and Japan) within the same ranges (however, the Japanese results should be interpreted conservatively owing to the limited sample size). Overweight among the mentally ill were marked in Nigeria. A parallelism of the incidence of overweight, CVD and diabetes with the occurrence in background populations was seen and was most marked in overweight. CONCLUSIONS: Overweight, CVD and DM were increased in schizophrenia spectrum disorders and affective disorders in all three cultures investigated (Western Europe, Nigeria and Japan). Lifestyle diseases were also seen in Nigeria and Japan. The results from this study indicate that cultural background might be seen as an important factor in dealing with lifestyle diseases among people with a severe mental illness, as it is in the general population.

Assessment of heterogeneity between European Populations: a Baltic and Danish replication case-control study of SNPs from a recent European ulcerative colitis genome wide association study.

BACKGROUND: Differences in the genetic architecture of inflammatory bowel disease between different European countries and ethnicities have previously been reported. In the present study, we wanted to assess the role of 11 newly identified UC risk variants, derived from a recent European UC genome wide association study (GWAS) (Franke et al., 2010), for 1) association with UC in the Nordic countries, 2) for population heterogeneity between the Nordic countries and the rest of Europe, and, 3) eventually, to drive some of the previous findings towards overall genome-wide significance. METHODS: Eleven SNPs were replicated in a Danish sample consisting of 560 UC patients and 796 controls and nine missing SNPs of the German GWAS study were successfully genotyped in the Baltic sample comprising 441 UC cases and 1156 controls. The independent replication data was then jointly analysed with the original data and systematic comparisons of the findings between ethnicities were made. Pearson's χ2, Breslow-Day (BD) and Cochran-Mantel-Haenszel (CMH) tests were used for association analyses and heterogeneity testing. RESULTS: The rs5771069 (IL17REL) SNP was not associated with UC in the Danish panel. The rs5771069 (IL17REL) SNP was significantly associated with UC in the combined Baltic, Danish and Norwegian UC study sample driven by the Norwegian panel (OR = 0.89, 95% CI: 0.79-0.98, P = 0.02). No association was found between rs7809799 (SMURF1/KPNA7) and UC (OR = 1.20, 95% CI: 0.95-1.52, P = 0.10) or between UC and all other remaining SNPs. We had 94% chance of detecting an association for rs7809799 (SMURF1/KPNA7) in the combined replication sample, whereas the power were 55% or lower for the remaining SNPs.Statistically significant PBD was found for OR heterogeneity between the combined Baltic, Danish, and Norwegian panel versus the combined German, British, Belgian, and Greek panel (rs7520292 (P = 0.001), rs12518307 (P = 0.007), and rs2395609 (TCP11) (P = 0.01), respectively).No SNP reached genome-wide significance in the combined analyses of all the panels. CONCLUSIONS: This replication study supports an important role for the studied rs5771069 (IL17REL) SNP, but not for rs7809799 (SMURF1/KPNA7), in UC etiology in the Danish, Baltic, and Norwegian populations. Significant genetic heterogeneity was suggested for rs7520292, rs12518307, and rs2395609 (TCP11) in UC etiology between the Nordic and the other European populations.

Polymorphisms in NF-κB, PXR, LXR, PPARγ and risk of inflammatory bowel disease.

AIM: To investigate the contribution of polymorphisms in nuclear receptors to risk of inflammatory bowel disease (IBD). METHODS: Genotypes of nuclear factor (NF)-κB (NFKB1) NFκB -94ins/del (rs28362491); peroxisome proliferator-activated receptor (PPAR)-γ (PPARγ) PPARγ Pro12Ala (rs 1801282) and C1431T (rs 3856806); pregnane X receptor (PXR) (NR1I2) PXR A-24381C (rs1523127), C8055T (2276707), and A7635G (rs 6785049); and liver X receptor (LXR) (NR1H2) LXR T-rs1405655-C and T-rs2695121-C were assessed in a Danish case-control study of 327 Crohn's disease patients, 495 ulcerative colitis (UC) patients, and 779 healthy controls. Odds ratio (OR) and 95% CI were estimated by logistic regression models. RESULTS: The PXR A7635G variant, the PPARγ Pro12Ala and LXR T-rs2695121-C homozygous variant genotypes were associated with risk of UC (OR: 1.31, 95% CI: 1.03-1.66, P = 0.03, OR: 2.30, 95% CI: 1.04-5.08, P = 0.04, and OR: 1.41, 95% CI: 1.00-1.98, P = 0.05, respectively) compared to the corresponding homozygous wild-type genotypes. Among never smokers, PXR A7635G and the LXR T-rs1405655-C and T-rs2695121-C variant genotypes were associated with risk of IBD (OR: 1.41, 95% CI: 1.05-1.91, P = 0.02, OR: 1.63, 95% CI: 1.21-2.20, P = 0.001, and OR: 2.02, 95% CI: 1.36-2.99, P = 0.0005, respectively) compared to the respective homozygous variant genotypes. PXR A7635G (rs6785049) variant genotype was associated with a higher risk of UC diagnosis before the age of 40 years and with a higher risk of extensive disease (OR: 1.34, 95% CI: 1.03-1.75 and OR: 2.49, 95% CI: 1.24-5.03, respectively). CONCLUSION: Common PXR and LXR polymorphisms may contribute to risk of IBD, especially among never smokers.

Common polymorphisms in the microsomal epoxide hydrolase and N-acetyltransferase 2 genes in association with inflammatory bowel disease in the Danish population.

INTRODUCTION: Chronic inflammatory bowel disease (IBD) is characterized by recurrent inflammation of the intestinal mucosa. Reactive molecules play a central role in altering the intestinal permeability, which may induce or sustain an immune response. Changes in detoxification of substances that causes epithelial damage may confer susceptibility to IBD. Hence, polymorphic enzymes involved in the detoxification processes may be risk factors of IBD. METHODS: The two biotransformation enzymes microsomal epoxide hydrolase and N-acetyltransferase 2 were genotyped using TaqMan based real-time PCR in 388 patients with Crohn's disease, 565 patients with ulcerative colitis and 796 healthy controls. RESULTS: No association was found between the genotypes of low microsomal epoxide hydrolase activity or slow N-acetyltransferase 2 acetylator status and IBD. An association was found between microsomal epoxide hydrolase and less than 40 years of age at diagnosis of Crohn's disease and microsomal epoxide hydrolase and azathiporine use in patients with ulcerative colitis. No other evident phenotypic associations were found for the two enzymes and either ulcerative colitis or Crohn's disease. A possible modification of smoking on microsomal epoxide hydrolase genotypes was found. CONCLUSION: Microsomal epoxide hydrolase and N-acetyltransferase 2 genotypes appear not to be individual risk factors of IBD, or to be important in relation to phenotypic characteristics of IBD.

Cyclooxygenase-2 (COX-2) polymorphisms and risk of inflammatory bowel disease in a Scottish and Danish case-control study.

BACKGROUND: Inflammatory bowel diseases (IBDs) are a result of interactions between luminal pathogens and the intestinal immune response. Cyclooxygenase-2 (COX-2) plays a key role in the regulation of the inflammatory response upon stimulation by luminal pathogens via Toll-like receptors. METHODS: Genotypes of the COX-2/PTGS2/PGHS2 A-1195G (rs689466), G-765C (rs20417), and T8473C (rs5275) polymorphisms were assessed in a Scottish and Danish case-control study including 732 Crohn's disease (CD) cases, 973 ulcerative colitis (UC) cases, and 1157 healthy controls using logistic regression. RESULTS: Carriers of the COX-2 A-1195G variant allele had increased risk of UC (odds ratio [OR], 95% confidence interval [CI] = 1.25 [1.02-1.54], P = 0.03) and of both UC and IBD among never smokers (OR [95% CI] = 1.47 [1.11-1.96], P = 0.01 and OR [95% CI] = 1.37 [1.06-1.77], P = 0.02, respectively). Furthermore, this variant genotype was associated with increased risk of diagnosis of UC before age 40 years and with extensive UC (OR [95% CI] = 1.34 [1.11-1.62], P = 0.002 and OR [95% CI] = 1.32 [1.03-1.69], P = 0.03, respectively). CONCLUSIONS: COX-2 A-1195G polymorphism was associated with the risk of UC, especially among never-smokers, suggesting that low activity of COX-2 may predispose to UC. Our results suggest that inclusion of smoking status may be essential for the evaluation of the role of genetic predisposition to IBD.

The polymorphism rs3024505 proximal to IL-10 is associated with risk of ulcerative colitis and Crohns disease in a Danish case-control study.

BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are characterized by a dysregulated inflammatory response to normal constituents of the intestinal flora in the genetically predisposed host. Heme oxygenase-1 (HO-1/HMOX1) is a powerful anti-inflammatory and anti-oxidant enzyme, whereas the pro-inflammatory interleukin 1 beta (IL-1 beta/IL1B) and anti-inflammatory interleukin 10 (IL-10/IL10) are key modulators for the initiation and maintenance of inflammation. We investigated whether single nucleotide polymorphisms (SNPs) in the IL-1 beta, IL-10, and HO-1 genes, together with smoking, were associated with risk of CD and UC. METHODS: Allele frequencies of the IL-1 beta T-31C (rs1143627), and IL-10 rs3024505, G-1082A (rs1800896), C-819T (rs1800871), and C-592A (rs1800872) and HO-1 A-413T (rs2071746) SNPs were assessed using a case-control design in a Danish cohort of 336 CD and 498 UC patients and 779 healthy controls. Odds ratio (OR) and 95% confidence interval (95% CI) were estimated by logistic regression models. RESULTS: Carriers of rs3024505, a marker polymorphism flanking the IL-10 gene, were at increased risk of CD (OR = 1.40, 95% CI: 1.06-1.85, P = 0.02) and UC (OR = 1.43, 95% CI: 1.12-1.82, P = 0.004) and, furthermore, with risk of a diagnosis of CD and UC at young age (OR = 1.47, 95% CI: 1.10-1.96) and OR = 1.35, 95% CI: 1.04-1.76), respectively). No association was found between the IL-1 beta, IL-10 G-1082A, C-819T, C-592A, and HO-1 gene polymorphisms and CD or UC. No consistent interactions between smoking status and CD or UC genotypes were demonstrated. CONCLUSIONS: The rs3024505 marker polymorphism flanking the IL-10 gene was significantly associated with risk of UC and CD, whereas no association was found between IL-1 beta or HO-1 gene polymorphisms and risk of CD and UC in this Danish study, suggesting that IL-10, but not IL-1 beta or HO-1, has a role in IBD etiology in this population.

Genetic variants of glutathione S-transferases mu, theta, and pi display no susceptibility to inflammatory bowel disease in the Danish population.

INTRODUCTION: A combination of genetic predisposition and interactions with environmental factors are believed to be responsible for disease phenotype and disease progression in inflammatory bowel diseases. The harmful effect of smoking and other environmental factors is believed to be highly dependent on the activity of detoxification enzymes. The aims of the study were to examine possible associations between the detoxifying glutathione S-transferases (GSTs) family mu, theta and pi gene variants and inflammatory bowel disease, and secondly to examine a potential genotype-genotype interaction between these variants. Genotype-disease phenotype associations and a possible interaction between genotype and cigarette smoking were also assessed. METHODS: Three hundred and eighty-eight patients with Crohn's disease (CD), 565 patients with ulcerative colitis (UC) and 796 healthy Danish controls were included in the study. Genomic DNA was used for genotyping of the GST genes using PCR or real-time PCR. RESULTS: No associations were found between GST genotypes and inflammatory bowel diseases. Neither did a combination of the GST genotypes reveal any associations. No genotype-disease phenotype associations were found. Smoking was positively associated with CD and negatively associated with UC. An interaction between smoking and GSTM1*0 genotype was found for UC, where the GSTM1*0 genotype appear to strengthen the protective effect of smoking on disease susceptibility. CONCLUSION: The GST genotypes do not seem to be important in susceptibility of inflammatory bowel disease in the Danish population. Nor did we find convincing evidence of associations between GST genotype and phenotypic features of inflammatory bowel diseases.

Cyclooxygenase-2, multidrug resistance 1, and breast cancer resistance protein gene polymorphisms and inflammatory bowel disease in the Danish population.

OBJECTIVE: Crohn's disease (CD) and ulcerative colitis (UC) are characterized by an impaired mucosal defence to normal constituents of the intestinal flora and a dysregulated inflammatory response. The purpose of the study was to investigate whether single nucleotide polymorphisms (SNPs) in genes involved in these processes were associated with CD and UC. MATERIAL AND METHODS: Allele frequencies of the cyclooxygenase 2 (COX-2/PTGS2/PGHS2) G-765C and breast cancer resistance protein (BCRP/ABCG2) C421A as well as allele and haplotype frequencies of multidrug resistance 1 (MDR1, ABCB1) SNPs G2677T/A, C3435T and G-rs3789243-A (intron 3) were assessed in a Danish case-control study comprising 373 CD and 541 UC patients and 796 healthy controls. RESULTS: Carriers of the homozygous COX-2 and MDR1 intron 3 variant had a relatively high risk of CD, odds ratio (95% CI) (OR (95% CI))=2.86 ((1.34-5.88) p=0.006) and 1.39 ((0.99-1.92) p=0.054), respectively, and for UC of 2.63 ((1.33-5.26) p=0.005) and 1.28 ((0.96-1.51) p=0.093), respectively, assuming complete dominance. No association was found for BCRP or other MDR1 SNPs, or for selected MDR1 haplotypes. No effect-modification of smoking habit at the time of diagnosis was found. CONCLUSIONS: An effect of the COX-2 polymorphism on both CD and UC was shown which is compatible with the presence of a recessive allele in linkage equilibrium with the SNP marker in the COX-2 gene. The polymorphism located in intron 3 of the MDR1 gene showed a weak association with CD, and a marginally suggestive association with UC.

Disease activity in pregnant women with Crohn's disease and birth outcomes: a regional Danish cohort study.

OBJECTIVES: CD is associated with increased risk of adverse birth outcomes, but existing studies have not assessed the impact of disease activity during pregnancy. We examined the impact of disease activity on birth outcomes: LBW, preterm birth, LBW at term, and CAs. METHODS: All births by CD women in North Jutland County, Denmark, from January 1, 1977 to December 31, 2005, were evaluated in a cohort study based on linkage between the Danish National Registry of Patients and the Medical Birth Registry. After identification of all births by CD women, review of medical records allowed collection of clinical details (including disease activity and drug therapy during pregnancy). The exposed cohort (N = 71) constituted pregnancies with low/moderate-high disease activity during pregnancy, and the unexposed cohort (N = 86) those with inactive disease. Logistic regression analyses were used to estimate the adjusted relative risks (with 95% confidence intervals) for adverse birth outcomes associated with disease activity in CD pregnancies. In subanalysis, we examined the impact of moderate-high activity. RESULTS: In women with disease activity, the adjusted risks of LBW, LBW at term, preterm birth, and CAs were 0.2 (0.0-2.6), 0.4 (0.0-3.7), 2.4 (0.6-9.5), and 0.8 (0.2-3.8), respectively. The crude risk of preterm birth was 3.4 (1.1-10.6) in those with moderate-high disease activity. CONCLUSIONS: Disease activity during pregnancy only increased the risk of preterm birth (especially in those with high disease activity). Further research is needed to assess the critical impact of disease activity in larger cohorts of CD women.

Increase in incidence and prevalence of inflammatory bowel disease in northern Denmark: a population-based study, 1978-2002.

OBJECTIVES: Although incidence rates of inflammatory bowel disease have been reported worldwide, few long-term population-based studies with current time-trend analyses exist. We therefore examined time trends in the incidence rate of inflammatory bowel disease in a 25-year study period, and estimated the prevalence in 2002. All patients diagnosed between 1978 and 2002 were included as incident cases (n=2,326) and all patients living in North Jutland County on 31 December 2002 were used to estimate prevalent cases (n=2,205). METHODS: Medical records of all patients diagnosed with ulcerative colitis and Crohn's disease in the North Jutland County Hospital Discharge Registry were reviewed to examine if the diagnostic criteria were fulfilled. Age-specific and gender-specific standardized incidence rates were calculated. RESULTS: For ulcerative colitis, incidence rates in women increased from 8.3 (95% confidence interval (CI): 6.7-9.9) in 1978-1982 to 17.0 (95% CI: 14.7-19.3) per 100,000 person-years in 1998-2002. The corresponding figures for men were 7.7 (95% CI: 6.1-9.3) and 16.7 (95% CI: 14.4-18.8) per 100,000 person-years. For Crohn's disease, the incidence rates in women increased from 4.1 (95% CI: 3.0-5.2) in 1978-1982 to 10.7 (95% CI: 8.8-12.5) per 100,000 person-years in 1998-2002. The corresponding figures for men were 3.2 (95% CI: 2.1-4.2) and 8.5 (95% CI: 6.9-10.2) per 100,000 person-years. The prevalence of ulcerative colitis and Crohn's disease was 294 and 151 per 100,000 inhabitants, respectively. CONCLUSIONS: A marked and parallel increase was seen in both ulcerative colitis and Crohn's disease in both genders during the last 25 years, with a corresponding high prevalence of both diseases.