Incidence Of Crohn's Disease Research Articles

Natural history of Crohn's disease in a population-based cohort from Cardiff (1986–2003): a study of changes in medical treatment and surgical resection rates

IntroductionBenefits of immunosuppressive therapy in Crohn's disease have been demonstrated in controlled trials; however, it is unclear whether these drugs alter the longer-term natural history of this condition.Aims and MethodsTo...

Crohn’s disease and ruminant farming. Got lactase?

Crohn's disease (CD) is a well known chronic pathological condition whose aetiology has remained unrecognized for nearly a century. Complex immune mechanisms in a specific genetic background causing an abnormal local inflammatory response are thought to be directly responsible for the clinical picture, but no external factor triggering such host responses has been identified. Humans lose the capability of breaking down milk lactose early in life and, afterwards, ingestion of large amounts of lactose causes a transient digestive illness known as lactose intolerance. Some human populations developed mutations for lactase persistence in adulthood that allowed better exploiting a product, milk, from not food-competitive domesticated species. This adaptation to dairy farming could have had as a collateral effect the exposure of human populations to a ruminant parasite with the ability to cause chronic inflammation in the intestine. Humans with a genetic susceptibility might develop a similar inflammatory disease caused by a defect in a highly conserved innate immunity mechanism. Data from different published sources regarding by country CD and type I diabetes incidence, lactose intolerance, livestock population, food production, Gross National Income and human population were submitted to Pearson and Kendall correlation, multiple regression and principal components analyses. Multiple regressions were also applied to a published 20-year time series for CD incidence in Japan. These analyses showed a strong association between country incidence of CD and frequency of lactase persistence as well as other ruminant production and consumption variables that further supports the meaning of those observations. Association of these variables with higher per capita income suggests that IBD incidence would be a side-effect of an otherwise highly successful adaptation. The evolutionarily plausible framework provided by this association with the species suffering a similar inflammatory bowel disease (IBD), its coincidence with the expanse of a cattle breed that could act as a Trojan horse, in addition to recent microbiological, immunological and therapeutical observations consistent with a slow infection type of pathogenesis, supports a mycobacterial aetiology of human IBD. Further research challenging the hypothesis of a shared aetiology by Mycobacterium avium subsp. paratuberculosis of human and ruminant IBD by increasing research on the pathogenesis of the latter and focusing on effective specific antibiotic or immune aetiological therapies seems to be the obvious next step. Either confirmation or rejection of the hypothesis presented here should create new knowledge that will bring closer the eradication of a cause of human and animal suffering.

Geographical variation of Crohn's disease residual incidence in the Province of Quebec, Canada

BackgroundCrohn's disease (CD) is clinically expressed as a chronic affection of the gastrointestinal tract currently known to have a multifactorial etiology involving a complex pathophysiological host response modulated by genetic susceptibilities, demographic determinants and environmental factors. With more than 20 cases per 100,000 person-years, the province of Quebec, Canada is among regions of the world with highest reported occurrence of CD in relation to other places where comparable estimates are available. This ecological study was designed to provide a medium-scale spatial exploration of CD incidence after accounting for the influence of known population and regional determinants. Health records of consulting patients in southern Quebec were compiled from 1995 to 2000 and used to estimate age and sex standardized rates per health area (n = 156). Various statistical models taking into account the regional effect of Jewish ethnicity, aboriginal ancestry, material deprivation, prescription for oral contraceptives, reportable enteric infection incidence, smoking as well as latitude and longitude locations were fitted.ResultsThe final regression model presented a coefficient of determination of 22.8% and there was evidence of an eastern trend in the residual incidence (p = 0.018). Overall, the smoothed residual incidence presented a heterogeneous spatial pattern with evidence of patches (multiple health areas) of high, low and contrasting values. Health areas with most extreme incidence residuals where also distributed over the whole province including one area in the metropolitan area of Montreal and others in surrounding areas.ConclusionsThese findings suggest that known populational and regional factors derived through census information only explain a limited fraction of the geographical variation of CD incidence and lead to speculate that the effects of these factors may be incompletely captured (imperfect construction of proxy variables) or that other important factors remain unmeasured. In this view, markers of genetic profiles of homogeneous sub-populations, and other factors linked to agroenvironmental microbial exposure should be further investigated. Once accounting for known factors, it would also be worth comparing adjacent geographical areas demonstrating abrupt changes in residual incidence rates to further explore effect linked to regional factors from those resulting from various reporting systems.

State of Research in Pediatric Gastroenterology, Hepatology, and Nutrition: 2010 and Beyond

State of Research in Pediatric Gastroenterology, Hepatology, and Nutrition: 2010 and Beyond

Fine-scale geographic variations of inflammatory bowel disease in France: Correlation with socioeconomic and house equipment variables

In a previous study we found a north-south gradient for Crohn's disease (CD) incidence in France. The aim of the present study was to determine if socioeconomic factors may influence the geographic distribution of CD and ulcerative colitis (UC) in France. Using the national health insurance databases, incidence rates of CD and UC were estimated for each of 341 metropolitan "job areas" in 2000-2002. Relationships between incidence rates and relevant contextual variables from the 1999 French census were tested for significance using a Poisson regression. Mapping of smoothed relative risks (sRR) for CD and UC at the scale of job areas, using a Bayesian approach and adjusting for significant contextual variables, was carried out in order to search for geographic variations. CD incidence rates were negatively related to the percentage of farmers and to the percentage of housing with bathroom and toilets and positively related to the unemployment rate and to the percentage of households below the poverty threshold. Mapping of sRR for CD showed a clear north-south gradient, which was slightly improved after including the percentage of farmers and the percentage of housing with toilets. In UC we found no significant correlation between either incidence and socioeconomic variables or incidence and house equipment variables, and there was no north-south gradient. However, there was a positive and significant correlation between CD and UC incidence. The present study shows that geographic risk factors of CD in France are northern latitude, nonrural areas, and areas with poor sanitary house equipment. Among these factors the most important is northern latitude.

Epidemiologic study on the current incidence of inflammatory bowel disease in Madrid

The incidence of inflammatory bowel disease (IBD) varies widely according to geographical area and has been reported to have increased in the last few years. No data are available on the current incidence of this disease in Madrid (Spain). to determine the incidence of inflammatory bowel disease in the area of influence of University Hospital Fundación Alcorcón (Madrid), and to compare our results with those from other Spanish and European series. A prospective, population-based study was performed to determine the incidence of IBD in the area of University Hospital Fundación Alcorcón in Madrid between 2003 and 2005. Total population: 213,587 inhabitants (177,490 older than 14 years). Crude rates and age- and sex-specific rates adjusted to the European standard population were calculated. A retrospective study (1998-2003) was also performed. A total of 69 cases were diagnosed -Crohn s disease (CD): 35, ulcerative colitis (UC): 33, indeterminate colitis: 1- in the prospective period. Crude rates of CD and UC were 7.92 and 7.47 cases/100,000 inhabitants/year, respectively (the population aged 0-14 years). Specific rates were 8.0 (95% CI, 7.03-8.97) and 7.47 (95% CI, 6.5-8.4), respectively. Mean age at diagnosis was 31.02+/- 10.76 and 39.91+/-16.19 years for CD and UC, respectively. Incidence in the retrospective study was 7.13 and 6.22 cases/100,000 inhabitants/year, respectively for CD and UC. The incidence of CD and UC in Madrid has increased in the last decades, with rates close to those in northern European countries for CD, higher than those recently published in Spanish prospective studies and similar to those previously described in Spain and southern countries for UC. Rates were higher in the prospective period than in the retrospective one.

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

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). 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 Crohn's 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. 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. 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.

Spatiotemporal Trends of Incidence Rates of Ulcerative Colities and Crohnʼs Disease

ISEE-0105 Background and Objective: Ulcerative colitis and Crohn's disease are assumed to be caused by a dysregulation in the immune system due to the commensal bacteria flora in genetically susceptible individuals. Incidence rates of the diseases, however, show large geographic and temporal variability. The temporal increase is often explained by the “hygiene hypothesis”, stating that reduced number of infections in early life will increase the likelihood for developing autoimmune diseases in adulthood, but this hypothesis is less likely to explain differences between countries. We will therefore decompose worldwide incidence rates of ulcerative colitis and Crohn's disease and correlate the incidence values to latitude, temperature, time, and economic conditions. Methods: We used published incidence studies of both Crohn's disease and ulcerative colitis from 1966 to 2007. The incidence rates were modelled as functions of latitude, mean annual temperature for the study areas, year of the study, and gross national product per capita. Results: Incidence rates of both diseases increase with increased gross national product per capita (P<0.001 and P = 0.046 for UC and CD). Incidence rates of ulcerative colitis were significantly related to latitude (P = 0.028). For Crohn's disease incidence rates were associated to both latitude and mean annual temperature (P = 0.016, P<0.001). Conclusions: Incidence rates for both diseases are related to economic changes and either latitude and/or mean annual temperature. Mean annual temperature is also assumed to reflect latitudinal change. We postulate that both economic and latitudinal variability are aspects of the same phenomena: microbial diversity. Improved economic conditions are related to a reduced microbial load. Species diversity is also known to be larger closer to equator than far from equator–the latitudinal diversity gradient. Reduced contact with commensal flora or “old friends”, due to reduced microbial load or ecological conditions could therefore explain the worldwide trends in incidence rates.

What is the Incidence of Small Bowel Cancer in Patients with Crohnʼs Disease and is There a Detection Bias?

Purpose: While Crohn's Disease (CD) is thought to predispose to adenocarcinomas of the small bowel, the prevalence and incidence of CD among patient with small bowel cancers (SBC), compared to cancer-free controls, has not been well studied at the population level. It is also not clear if this increased incidence is due to detection bias. The first objective is to estimate the prevalence of CD in persons with adenocarcinomas of the small bowel compared to cancer-free controls in a population-based, case-control study of an older population (>65 years). Our second objective is to study the incidence of SBC compared to non-GI cancers in patients with Crohn's disease to evaluate for detection bias. Methods: Cases and controls were identified from the SEER-Medicare database. Cases consisted of persons 67 and older in the SEER catchment area and in the Medicare claims data base who were diagnosed with SBC between 1994-1999. Two sets of controls were identified: one set was cancer free and a second set with non-GI cancers. CD cases were identified from ICD-9 codes on Medicare outpatient, office, and inpatient claims data during the two year window prior to the date of cancer diagnosis for cases or a randomly selected reference date for controls. Incidence was measured by comparing the number of new cases of small bowel cancer divided by the number of person-years at risk among persons with CD and those without CD. Results: The final sample consisted of 923 cases of SBC, 10,800 cases of other non-GI tract cancers, and 142,273 cancer free controls. Overall 1.6% of small bowel cancer cases carried a diagnosis of CD, which was nearly 12 times the prevalence of CD among cancer-free controls (p-value<0.001). In multivariable logistic regression analysis there was a significant association between CD and SBC (OR 11.24; 95% CI 6.07- 20.84; p-value<0.001). We found the annual incidence of SBC was 143 per 100,000 person-years (95% CI 120-168/ 100,000 person-years) among those with CD, and 1.1 per 100,000 person-years (0.25.5/ 100,000 person-years) among those without CD, yielding an incidence rate ratio of 120. Non-GI cancer controls had a nearly 1.5 fold higher prevalence of CD compared to cancer-free controls (p-value 0.03). In multivariable logistic regression analysis, there was a modest significant association of CD (OR 1.69; 95% CI 1.06-2.70; p-value 0.02) with non-GI cancer controls compared to cancer-free controls. Conclusion: The prevalence rate and incidence rate ratio for SBC among elderly persons with CD is strikingly high, even though the absolute risk remains low. There is also an increased prevalence of CD in persons with non-GI cancers suggesting either detection bias or a truly higher prevalence of CD among non-GI tract cancer controls.

Environmental risk factors in Crohn's disease and ulcerative colitis: an update

Rapid increase in Crohn's disease (CD) and ulcerative colitis (UC) incidence in developed countries, occurrence of CD in spouses and lack of complete concordance in monozygotic twins are strong arguments for the role of environmental factors in inflammatory bowel disease (IBD). Only two environmental factors have an established role in IBD. Smoking is a risk factor for CD and a protective factor for UC; appendectomy is a protective factor for UC. Many other environmental factors for IBD have been investigated. These are infectious agents, diet, drugs, stress and socio-economic factors. They are detailed in this paper. Among them, adherent invasive E. coli, infectious gastroenteritis, oral contraceptives and antibiotics could play a role in CD. To date, three theories integrate environmental factors to pathogenesis of IBD: hygiene, infection and cold chain. Much work remains to be done to identify risk factors for IBD. As exemplified by smoking, research of environmental risk factors of IBD is useful since it may lead to an improved disease course among patients and perhaps, to appropriate prevention among predisposed subjects. Further studies in this field are eagerly awaited.

Epidemiology of Pediatric Chronic Inflammatory Bowel Disease in Central and Western Slovenia, 1994–2005

The aim of this study was to determine the epidemiological and clinical characteristics of inflammatory bowel disease (IBD) in children in central and western Slovenia during a 12-year period (1994-2005). The medical records of patients with newly diagnosed IBD during the period of 1994-2005 were retrospectively reviewed. In the 12-year study period, 137 children received new diagnoses of IBD, 60% had Crohn disease (CD), 28% had ulcerative colitis (UC), and 12% had indeterminate colitis (IC). The mean annual incidence of IBD for the whole 12-year period was 4.03/100,000 children; for CD 2.42, for UC 1.14, and for IC 0.47. The annual incidence of IBD rose from 3.04 in the period 1994-1999 to 5.14 in the period 2000-2005. The incidences of CD, UC, and IC rose from 1.99, 0.77, and 0.28, respectively, in the first 6 years to 2.88, 1.57, and 0.69, respectively, in the second 6-year period. The most common type of CD at presentation was inflammatory. Pancolitis was the most frequent form of UC. Almost half of the patients had a severe form of CD at its onset. The incidence of total pediatric IBD in central and western Slovenia is high and seems to be still rising. CD is the most prevalent form of IBD; its incidence is comparable with that reported in other central and western European countries. The incidences of UC and IC are rising more rapidly than the incidence of CD.

114 The Changing Pattern of Crohn's Disease Incidence According to Age in Northern France: A Constant Increase in the 0-19 Year's Age Group (1988-2005)

114 The Changing Pattern of Crohn's Disease Incidence According to Age in Northern France: A Constant Increase in the 0-19 Year's Age Group (1988-2005)

115 Geographic Distribution of Inflammatory Bowel Disease (IBD) in France and Sunlight Exposure

Exposure to the sun may protect against multiple sclerosis Br Med J 2003;327:334). In France, geographic distributions of multiple sclerosis and Crohn disease(CD)are similar (IBD2006;12:218 and J Neurol Neurosurg Psychiatry 2007;78:707). Aim: to determine if geographic distribution of CD and UC is influenced by sun exposure. Methods: This study included patients to whom IBD reimbursement was attributed in France, between 2000 and 2002. Data provided relate to age, sex, postcode area of residence and IBD type. Ground UV from sunshine data was expressed in kJ/m2 and was provided by month and by French “departement” for the years 1984 to 2002. We calculated a mean monthly UV dose for the studied period, which was classified into quintiles, and linked with incidence data tabulated by departement. Age and sex-adjusted incidence rate ratios (IRR), with their 95% confidence intervals, were estimated per quintile of UV dose by using the Poisson regression. A spatial analysis, with Bayesian approach was then performed. Results: 14,213 new patients with CD (8,172 women) and 12,452 with UC (5,984 women) were registered by the 5 health insurance funds. There was a negative correlation between age and gender-adjusted CD incidence rates, and local UV dose (IRR= 1.42, 95%CI [1.27 1.58] for the 1st quintile, IRR = 1.12, 95%CI [1.00 1.26], for the 2nd quintile, IRR = 0.90, 95%CI [0.78 1.04] for the 3rd quintile, IRR = 0.85, 95%CI [0.74 0.98], for the 4th quintile, (5th quintile = reference). Local UV dose improved the Bayesian model of geographic distribution of CD and its effect was stronger than local spatial autocorrelation. As shown in the figure, areas with a smoothed relative risk (sRR)of CD significantly higher than 1 corresponded to departments with low sunlight exposure, whereas those with high sunlight exposure had sRR either lower than 1 or not significantly different from 1. Conclusion. Low sunlight exposure could be a risk factor for CD.

116 Phylogenetic Fingerprinting of the Faecal Microbiota in IBD-Patients Using the Human Intestinal Tract (HIT) Chip Approach: A Twin Study

Exposure to the sun may protect against multiple sclerosis Br Med J 2003;327:334). In France, geographic distributions of multiple sclerosis and Crohn disease(CD)are similar (IBD2006;12:218 and J Neurol Neurosurg Psychiatry 2007;78:707). Aim: to determine if geographic distribution of CD and UC is influenced by sun exposure. Methods: This study included patients to whom IBD reimbursement was attributed in France, between 2000 and 2002. Data provided relate to age, sex, postcode area of residence and IBD type. Ground UV from sunshine data was expressed in kJ/m2 and was provided by month and by French “departement” for the years 1984 to 2002. We calculated a mean monthly UV dose for the studied period, which was classified into quintiles, and linked with incidence data tabulated by departement. Age and sex-adjusted incidence rate ratios (IRR), with their 95% confidence intervals, were estimated per quintile of UV dose by using the Poisson regression. A spatial analysis, with Bayesian approach was then performed. Results: 14,213 new patients with CD (8,172 women) and 12,452 with UC (5,984 women) were registered by the 5 health insurance funds. There was a negative correlation between age and gender-adjusted CD incidence rates, and local UV dose (IRR= 1.42, 95%CI [1.27 1.58] for the 1st quintile, IRR = 1.12, 95%CI [1.00 1.26], for the 2nd quintile, IRR = 0.90, 95%CI [0.78 1.04] for the 3rd quintile, IRR = 0.85, 95%CI [0.74 0.98], for the 4th quintile, (5th quintile = reference). Local UV dose improved the Bayesian model of geographic distribution of CD and its effect was stronger than local spatial autocorrelation. As shown in the figure, areas with a smoothed relative risk (sRR)of CD significantly higher than 1 corresponded to departments with low sunlight exposure, whereas those with high sunlight exposure had sRR either lower than 1 or not significantly different from 1. Conclusion. Low sunlight exposure could be a risk factor for CD.

P214 - The changing pattern of Crohn's disease incidence according to age in Northern France: a constant increase in the 0 19 years age group (1988 2005)

s of the 4th Congress of ECCO the European Crohn’s and Colitis Organisation S95 (EDSS). IBD phenotypes at diagnosis were compared to those of isolated cases reported in EPIMAD registry. MS and IBD phenotypes at maximal follow-up were compared to data of the literature [3,4]. Results: Between 1966 and 2006, 25 patients with IBD and MS were identified, significantly higher than expected number (16, p = 0.014). Among these 25 cases (14 F and 11 M), 10 had Crohn’s disease (CD), 14 ulcerative colitis (UC) and 1 indeterminate colitis. The neurological symptoms began before the IBD in 70%. Median age at diagnosis of MS and IBD was 28 yrs [23 38] and 30 [23 43], no different of that of isolated cases. Median follow-up duration of MS and IBD was 8 yrs [7 21] and 10 [5 13]. Familial history of dysimmune diseases, MS and IBD was observed in 39, 25 and 8 of cases. MS phenotype was less advanced than in isolated cases (RR 76% vs 50%, SP 19% vs 35% and PP 5% vs 15%;p = 0.05) and the median EDSS score was lower (2.5 vs 4;p = 0.03). In cases of UC/MS, UC location at diagnosis was not different but UC location at maximal follow-up was less extensive (E3:15 vs 42%;p < 0.005) and none patient was colectomized. Among the 11 (44%) patients with immunosuppressive treatment, 9 had neurological symptoms before IBD symptoms. Conclusions: This study confirmed in our population that the concurrence of IBD and MS was greater than expected. There was a frequent association with other familial dysimmune disorders, suggesting a possible common genetic susceptibility. IBD phenotypes were less extensive than in isolated IBD and MS was less disabling at maximal follow-up. There was no association between disease onset and treatment of the other inflammation condition. Larger population-based studies are needed to confirm our findings.

10 - Patterns and predictors of dosage increase in patients treated with adalimumab for Crohn's disease in the United States

s of the 4th Congress of ECCO the European Crohn’s and Colitis Organisation S7 the Poisson regression, for CD and UC. A spatial analysis, with Bayesian approach was then performed. Results: From January 1, 2000 to December 31, 2002, 14,213 new patients with CD (8,172 women) and 12,452 new patients with UC (5,984 women) were registered by the five health insurance funds, among the overall insured population of 58,157,661. There was a significant negative correlation between age and gender-adjusted CD incidence rates, and local UV dose (IRR = 1.42, 95%CI [1.27 1.58] for the first quintile, IRR = 1.12, 95%CI [1.00 1.26] for the second quintile, IRR = 0.90, 95%CI [0.78 1.04] for the third quintile, IRR = 0.85, 95%CI [0.74 0.98], for the fourth quintile (fifth quintile = reference). Local UV dose improved the Bayesian model of geographic distribution of CD and the effect of local UV dose was stronger than the effect of local spatial autocorrelation. Variations of smoothed relative risks (sRR) of CD in both sexes according to the sunlight exposure are displayed in the figure. Areas with a sRR significantly higher than 1 corresponded to departments with low sunlight exposure, whereas those with high sunlight exposure had sRR either lower than 1 or not significantly different from 1. Conclusion: These results suggest that low sunlight exposure is a risk factor for CD. This hypothesis should be investigated within case-control or cohort studies. 10 Patterns and predictors of dosage increase in patients treated with adalimumab for Crohn’s disease in the United States E.V. Loftus Jr.1 *, X. Pan2, P. Zurawski3, P. Mulani3, J. Chao3. 1Miles & Shirley Fiterman Center for Digestive Diseases, Mayo Clinic, Rochester, MN, USA, 2University of Iowa, Iowa City, IA, USA, 3Abbott Laboratories, Abbott Park, IL, USA Introduction: Adalimumab, a fully human anti-tumor necrosis factor monoclonal antibody, is an effective treatment for Crohn’s disease (CD). After induction therapy, adalimumab 40mg is usually used as every-other-week dosing for maintenance therapy. In a large clinical trial, 27% of patients increased their adalimumab dosage to weekly within 1 year [1]. Information regarding the dosage pattern of adalimumab in real-world clinical practice is of interest. Our objective was to determine the dosage pattern of adalimumab in patients with CD covered by specialty pharmacies in the United States and to identify predictors for dosage increase to a weekly regimen. Methods: Using data from a large specialty pharmacydispensing database in the United States from March 2007 to July 2008, we studied patients with CD (ICD-9: 555) whose first dose of adalimumab was on or after 1 March 2007. New users of adalimumab were included in the analysis. Adalimumab maintenance therapy was defined as 3 dispensing events of adalimumab within 1 year. A weekly dosage regimen of adalimumab was defined as 2 consecutive weekly doses after the first dispensing event. Descriptive weekly dosing rates were determined by calculating the ratio of patients with weekly dosing to the total sample of adalimumab-treated patients. To control for the impact of variable follow-up times, Kaplan Meier analysis was used to estimate the weekly dosing rate for a 12-month period. To identify possible predictors for weekly dosing, a Cox proportional hazards regression model was developed to examine the impact of age, sex, geographic region, and use of a 160/80-mg induction dose on the weekly dosing rate. Results: Of 1335 patients with CD who received adalimumab as maintenance therapy, 11.3% (n = 151) had weekly dosing at any time during the study period. The 12-month cumulative risk of weekly dosing was 15.5% (Kaplan Meier analysis). The Cox proportional hazards model demonstrated that geographic region and not starting on 160/80mg for induction therapy were significant predictors for weekly adalimumab use. Patients who received 160/80mg as induction therapy were approximately half as likely to receive weekly dosing as those who didn’t start with 160/80mg (Hazards ratio [HR] = 0.48, 95%CI: 0.33 0.69, non-160/80-mg user as reference group, p < 0.0001). The western and southern regions of the United States had significantly lower rates of weekly dosing than did the northeastern region (HR = 0.50, 95%CI: 0.27 0.90 and HR= 0.46, 95%CI: 0.31 0.69, respectively, with northeast as reference group; both p < 0.05). Conclusions: The rate of adalimumab weekly dosing in clinical practice is less than the rates observed in clinical trials. Patients who received 160/80-mg induction therapy were significantly less likely to receive weekly dosing, and geographic variation in weekly adalimumab dosing rates was observed.

9 - Geographic distribution of inflammatory bowel disease (IBD) in France is influenced by sunlight exposure

s of the 4th Congress of ECCO the European Crohn’s and Colitis Organisation S7 the Poisson regression, for CD and UC. A spatial analysis, with Bayesian approach was then performed. Results: From January 1, 2000 to December 31, 2002, 14,213 new patients with CD (8,172 women) and 12,452 new patients with UC (5,984 women) were registered by the five health insurance funds, among the overall insured population of 58,157,661. There was a significant negative correlation between age and gender-adjusted CD incidence rates, and local UV dose (IRR = 1.42, 95%CI [1.27 1.58] for the first quintile, IRR = 1.12, 95%CI [1.00 1.26] for the second quintile, IRR = 0.90, 95%CI [0.78 1.04] for the third quintile, IRR = 0.85, 95%CI [0.74 0.98], for the fourth quintile (fifth quintile = reference). Local UV dose improved the Bayesian model of geographic distribution of CD and the effect of local UV dose was stronger than the effect of local spatial autocorrelation. Variations of smoothed relative risks (sRR) of CD in both sexes according to the sunlight exposure are displayed in the figure. Areas with a sRR significantly higher than 1 corresponded to departments with low sunlight exposure, whereas those with high sunlight exposure had sRR either lower than 1 or not significantly different from 1. Conclusion: These results suggest that low sunlight exposure is a risk factor for CD. This hypothesis should be investigated within case-control or cohort studies. 10 Patterns and predictors of dosage increase in patients treated with adalimumab for Crohn’s disease in the United States E.V. Loftus Jr.1 *, X. Pan2, P. Zurawski3, P. Mulani3, J. Chao3. 1Miles & Shirley Fiterman Center for Digestive Diseases, Mayo Clinic, Rochester, MN, USA, 2University of Iowa, Iowa City, IA, USA, 3Abbott Laboratories, Abbott Park, IL, USA Introduction: Adalimumab, a fully human anti-tumor necrosis factor monoclonal antibody, is an effective treatment for Crohn’s disease (CD). After induction therapy, adalimumab 40mg is usually used as every-other-week dosing for maintenance therapy. In a large clinical trial, 27% of patients increased their adalimumab dosage to weekly within 1 year [1]. Information regarding the dosage pattern of adalimumab in real-world clinical practice is of interest. Our objective was to determine the dosage pattern of adalimumab in patients with CD covered by specialty pharmacies in the United States and to identify predictors for dosage increase to a weekly regimen. Methods: Using data from a large specialty pharmacydispensing database in the United States from March 2007 to July 2008, we studied patients with CD (ICD-9: 555) whose first dose of adalimumab was on or after 1 March 2007. New users of adalimumab were included in the analysis. Adalimumab maintenance therapy was defined as 3 dispensing events of adalimumab within 1 year. A weekly dosage regimen of adalimumab was defined as 2 consecutive weekly doses after the first dispensing event. Descriptive weekly dosing rates were determined by calculating the ratio of patients with weekly dosing to the total sample of adalimumab-treated patients. To control for the impact of variable follow-up times, Kaplan Meier analysis was used to estimate the weekly dosing rate for a 12-month period. To identify possible predictors for weekly dosing, a Cox proportional hazards regression model was developed to examine the impact of age, sex, geographic region, and use of a 160/80-mg induction dose on the weekly dosing rate. Results: Of 1335 patients with CD who received adalimumab as maintenance therapy, 11.3% (n = 151) had weekly dosing at any time during the study period. The 12-month cumulative risk of weekly dosing was 15.5% (Kaplan Meier analysis). The Cox proportional hazards model demonstrated that geographic region and not starting on 160/80mg for induction therapy were significant predictors for weekly adalimumab use. Patients who received 160/80mg as induction therapy were approximately half as likely to receive weekly dosing as those who didn’t start with 160/80mg (Hazards ratio [HR] = 0.48, 95%CI: 0.33 0.69, non-160/80-mg user as reference group, p < 0.0001). The western and southern regions of the United States had significantly lower rates of weekly dosing than did the northeastern region (HR = 0.50, 95%CI: 0.27 0.90 and HR= 0.46, 95%CI: 0.31 0.69, respectively, with northeast as reference group; both p < 0.05). Conclusions: The rate of adalimumab weekly dosing in clinical practice is less than the rates observed in clinical trials. Patients who received 160/80-mg induction therapy were significantly less likely to receive weekly dosing, and geographic variation in weekly adalimumab dosing rates was observed.

A characterization in childhood inflammatory bowel disease, a new population-based inception cohort from South-Eastern Norway, 2005–07, showing increased incidence in Crohn's disease

Objective. Owing to rising incidence rates in inflammatory bowel disease (IBD), there has been increased interest in causal relationships in pediatric disease. The present population-based inception cohort was recruited in the Oslo area from 2005 to 2007, with the aim of conducting a detailed characterization of treatment-naïve patients at diagnosis. Material and methods. After an invitation was extended to all general practitioners in the catchment area, patients aged <18 years with suspected IBD were diagnosed by proximal and distal endoscopy, MRI, demographic, clinical, and histological and molecular characteristics. Symptomatic non-IBD patients served as controls. Results. Of 100 pediatric patients, 62 had IBD (39 Crohn's disease (CD), 19 ulcerative colitis (UC), 4 IBD unclassified (IBDU)) and 38 other diseases. Median age at diagnosis for IBD was 13.1 years (56.4% males), median symptom duration 6 months, and 69% L3 (Vienna classification). With 195,000 children aged <18 years in the catchment area, the incidence rate of IBD per 100,000/years inhabitants was 10.9 (6.8 for CD, 3.6 for UC, and 0.6 IBDU) and for those aged <16 years (178,500) the incidence rate was 10.6. The higher NOD2 allele frequency among children may partly contribute to the increase. Conclusions. The results indicate a marked rise in the incidence of CD in contrast to no increase in UC in South-Eastern Norway, compared with the figures from the last 15 years. Time from onset of symptoms to diagnosis still represents a challenge for early characterization in IBD.

Crohn's disease in a Saudi outpatient population: is it still rare?

Background/Aim:To determine the epidemiology of Crohn's disease (CD) in an outpatient clinic and compare it with data previously reported from different centers in the Kingdom of Saudi Arabia and outside.Materials and Methods:The medical records of all patients with CD seen in the clinic in the period from January 1993 through December 2007 were reviewed. The demographic, clinical data and methods of diagnosis were retrieved.Results:Over a period of 15 years, we saw 133 Saudi patients with CD. They were predominantly young, with a median age of 26.2 years and male preponderance (2.3:1). The final diagnosis was established within 1 week of presentation in 47% of the patients. The leading symptoms were abdominal pain (88%), diarrhea (70%), bloating (61%), rectal bleeding (50%), weight loss (33%), constipation (24%) and perianal disease (23%). The diagnosis was established by endoscopy and histopathology. Ileocecal involvement was encountered in 40% of the patients.Conclusion:From the current study, it is obviously possible to diagnose a large proportion of patients with CD in a gastroenterology outpatient clinic. The data revealed a strikingly increased incidence of CD in a mainly young Saudi population in the past few years.

Association between early-life factors and risk of child-onset Crohnʼs disease among victorian children born 1983–1998: A birth cohort study

The incidence of Crohn's disease (CD) with onset before age 16 has increased. Several perinatal characteristics have been associated with CD. Our objective was to examine the temporal change in CD incidence by period of birth and the extent that this could be attributed to perinatal characteristics associated with higher CD risk. A record linkage study was conducted utilizing the perinatal records of Victorian births 1983-1998 inclusive and a state-based CD registry. Proportional hazards models were used to investigate the perinatal factors in relation to the onset of CD by age 16. Further, a nested case control study was conducted to examine the association between sibling exposure and CD risk. The CD incidence rate for births 1983-1998 was 2.01 (95% confidence interval [CI] 1.79, 2.27) per 100,000 child-years. A birth cohort effect was demonstrated, with higher CD risk for 1992-1998 versus 1983-1991 births (hazard ratio [HR] 1.56; 95% CI 1.18, 2.06). Perinatal characteristics associated with higher CD risk included urban location, higher socioeconomic status, married mother, a congenital abnormality and delivery by elective cesarean section. Sibling exposure during the first 6 years of life was not associated with CD risk. The increased CD incidence among more recent births was not accounted for by changes in these measured perinatal factors. The temporal increase in CD incidence documented for births up to 1990 has continued for children born after 1991 and was not accounted for by temporal changes in the measured perinatal factors.