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The Risk of Crohn's Disease Progression Towards Intestinal Complications in an Asian Cohort
Tu1270
Clinical and Genetic Factors Predict Severe Disease: A Novel Composite Severity Index Anne M. Phillips, Ian D. Arnott, Tim Heron, Shirley Cleary, Craig Mowat, Hilary Clark, Nicholas Lewin-Koh, Jack Satsangi
The Risk of Crohn's Disease Progression Towards Intestinal Complications in an Asian Cohort Wei Lin Tay, Kelvin T. Thia, John C. Allen, San Choon Kong, Khoon-Lin Ling, Choon-Jin Ooi
Introduction: Crohn's disease is an incurable progressive disease with marked heterogeneity in outcome. Identifying patients at diagnosis at high risk of poor outcomes would allow treatment stratification. The most widely used definition of severe disease lacks discrimination with 85.2% of patients meeting the criteria for ‘disabling’ disease (Beaugerie et al. Gastroenterology 130: 650-656). A more discriminant composite severity score would benefit clinical research and aid clinical decision making. Methods: Based on a consensus of 5 clinicians, we designed a composite severity score, assessed over the 5 years after diagnosis, with a total possible score 1-16. The score was applied retrospectively in 367 CD patients who were also genotyped for 32 CD susceptibility loci. The severity score that would encompass the 50% of patients with the highest score was defined, and factors present at diagnosis both clinical and genetic - were assessed by the chi squared test for their ability to predict being in the more severe disease category. CD was classified according to the Montreal classification. Results: 367 CD patients (median age at Dx 30.8 (IQR 22.9-46.1)) were assessed. 249 patients had full data available for the first 5 years after diagnosis. The mean severity score was 6.3 (95% CI 5.9-6.6). Patients with a score >6 were defined as having more severe disease. Patients with more severe disease were younger at diagnosis (p=0.0004 for trend, odds ratio (OR) A1 v A2=4.42 (95% CI 1.4-13.9)) and had an ileal (p=0.0025, OR=2.2 (95% CI 1.32-3.68)) and upper GI location disease location at diagnosis (p=0.0008, OR=5.3 95% CI 1.9-14.7). Perianal disease at diagnosis approached but did not achieve statistical significance (p=0.052). Only rs9286879 (p=0.0085) and rs17582416 (p=0.0448) were observed more frequently in patients with severe disease. The need for steroids at diagnosis, having a first degree relative with IBD, needing surgery at diagnosis or smoking status at diagnosis did not differ between the groups. Conclusion: This index discriminates more effectively than existing definitions between severity groups. Disease location, age at diagnosis and genetic markers are associated with more severe disease but validation of these factors is needed in a separate cohort. Severity score (first 5 years after diagnosis)
BACKGROUND: An emergence of Crohn's disease has been reported in Asia over the past decade. While the natural history of Crohn's disease had been well described in Western series, data for Asian patients is scant. AIMS: We sought to assess the rate of intestinal complications and their associated risk factors in an Asian cohort. METHODS: This is a retrospective study of Crohn's disease patients currently on active follow-up at our centre. Records from the period 12/1975 to 11/2010 were evaluated . Medical records were reviewed and the clinical phenotypes at diagnosis of patients were categorized according to the Montreal classification. Baseline putative risk factors at and within 90 days of diagnosis such as age, sex, race, disease location and perianal disease were documented. The cumulative probabilities of developing intestinal stricturing and/or penetrating events were estimated using the Kaplan-Meier method and Cox proportional hazards regression was used to assess associations between baseline risk factors and progression to intestinal complication. RESULTS: The baseline clinical characteristics of 138 patients are as shown in Table 1. At baseline, 77.5% had nonstricturing nonpenetrating disease, 13.8% had stricturing disease, and 8.7% had penetrating disease. The cumulative risks of developing either complications were 22.5% (95% CI: 15.4-29.6) at or within 90 days, 29.4% (95% CI: 21.4-37.3) at 5 years, and 37.0% (95% CI: 27.7-46.3) at 10 years and 43.0% (95% CI: 31.2-54.7) at 20 years after diagnosis. Among 107 patients with nonstricturing, nonpenetrating disease at baseline, 17 were observed to experience a change in disease behavior after the first 90 days from diagnosis. The cumulative risks of developing either a stricturing or penetrating complication among those with nonstricturing nonpenetrating phenotype at diagnosis were 8.9% (95% CI: 2.9-14.9) at 5 years, 18.7% (95% CI: 9.4-28.1) at 10 years, and 26.5% (95% CI: 12.9-40.0) at 20 years. Among the 48 patients in the entire cohort with stricturing and penetrating phenotype, 32 (66.7%) underwent bowel resection surgery for management of Crohn's disease-related complications. None of the baseline risk factors were found to be significantly associated with the risk of intestinal complications. CONCLUSIONS: In this Asian tertiary study, 22.5% of patients with Crohn's disease experienced stricturing or penetrating complications within 90 days after diagnosis and 43% experienced intestinal complications 20 years after diagnosis. The complication rates observed resemble Western cohort studies. The surgical morbidities were substantial with 2 in 3 patients requiring bowel resection after a change in behavior. Predictive risk factors for complications will need to be confirmed in a larger Asian cohort.
Tu1269 New Insights Into the Genetic Basis for Variation in Crohn's Disease (CD) Phenotype in a Population-Based Study John D. Ryan, Mark S. Silverberg, Wei Xu, John R. Walker, Lesley A. Graff, Jason Ediger, Norine Miller, Linda Rogala, Michael Sargent, Rachel Carr, Joanne M. Stempak, Patricia E. Rawsthorne, Charles N. Bernstein Aims: In this study we evaluate for associations between clinical variables and IBD-related SNPs and specific disease phenotypes in a well-characterized, population-based CD cohort. Methods: Clinical data was obtained on a prospectively collected patient population from the Manitoba IBD Cohort Study (n=182, 112 females;70 males. These subjects were enrolled within 7 years of diagnosis (mean 4.3 yrs) and have been followed prsopectively every 6 months with surveys and annually with in-person interviews. Phenotyping and categorization of patients was performed using the Montreal Classification. DNA collected on these subjects was genotyped and the allele frequencies of known IBD-associated SNPs were determined. Analysis was performed to identify the SNPs associated with disease location and behaviour, surgical history, smoking status and psychological variables. Results presented are uncorrected. P value <0.01 was considered significant. Results: The distribution of patients within Montreal Classification categories was: A1=10%, A2=64%, A3=26%; L1=43%, L2=22%, L3= 34%, L4=7%; B1=45%, B2=33%, B3=22%, P=23%. Of the clinical variables, disease behaviour was strongly associated with surgery p <0.0001, OR=7.29) and smoking status (p=0.01, OR=2.09). Perianal disease was also associated with younger age at diagnosis (p=0.004). Subjects undergoing surgery tended to have higher childhood adversity impact p = 0.06, OR=1.81). Lifetime history of depression p = 0.07, OR=1.75) tended to be more common in patients with colonic involvement. For the genetic analysis, a SNP in DLG5 was associated with colonic and ileocolonic disease, while SNPs in RAC2 and NOX3 were associated with disease confined to the terminal ileum. SNPs in NR3C1, SCUBE3 and CDH19 were associated with disease behaviour. SNPs in TLR9, PARD3 and DLG5 were associated with perianal disease. 2 SNPs at the 5q31 locus and a SNP at SERPINA1 were associated with early surgery (< 3 years from diagnosis as opposed to no surgery) whereas one SNP in NOX4 was associated with no surgical intervention. Conclusions: Psychosocial variables were associated with colonic disease and early surgery but require further exploration in a larger sample size. Early surgery occurs in those harboring mutations at the 5q31 locus and at a SNP at SERPINA1 Disease location and behaviour was associated with a number of SNPs, some previously not reported.
Tu1271 Determinants Contributing to Fatigue in IBD Patients Lauran Vogelaar, Adriaan van 't Spijker, Ernst J. Kuipers, Christien J. van der Woude Background: Inflammatory bowel disease (IBD) patients (pts) suffer from a disabling disease which negatively influences their quality of life. Fatigue is a common symptom in IBD pts and contributes to this decreased quality of life. Aim: To assess underlying factors contributing to fatigue in IBD pts. Patients and methods: Group A included an adult IBD patient group that anonymously completed an online survey on fatigue. A second group included patients from the IBD-outpatient clinic, these patients filled out a paper version of this survey (group B). The survey included the Checklist Individual Strength (CIS) (fatigue: CIS score ≥ 35; non-fatigue CIS score < 35), the Hospital Anxiety and Depression Scale (HADS), the HarveyBradshaw Index and the Ulcerative Colitis Index for disease activity and information on current medication use. For statistical analysis descriptive statistics, univariate and multivariate logistic regression were used. Results: In total 977 pts were included. In group A 432 pts completed the survey (75% female, 57.9% Crohn's disease (CD), 42.1% ulcerative colitis (UC), mean age 40 (SD 12.6). The mean CIS score was 46 (range 13-56). Overall, 90.7% of the patients experienced fatigue. In group A 54 pts (12.5%) had a clinical depression and 99 pts (22.9%) with clinical anxiety. In contrast to non-fatigue pts, CD pts suffering from fatigue were significantly more depressive (OR 1.57; 95% CI 1.22-2.01), and had disease activity (OR 1.30; 95% CI 1.07-1.59). The results were similar in UC, however
S-783
AGA Abstracts
AGA Abstracts
Tu1268
Clinical and Genetic Factors Predict Severe Disease: A Novel Composite Severity Index Anne M. Phillips, Ian D. Arnott, Tim Heron, Shirley Cleary, Craig Mowat, Hilary Clark, Nicholas Lewin-Koh, Jack Satsangi
The Risk of Crohn's Disease Progression Towards Intestinal Complications in an Asian Cohort Wei Lin Tay, Kelvin T. Thia, John C. Allen, San Choon Kong, Khoon-Lin Ling, Choon-Jin Ooi
Introduction: Crohn's disease is an incurable progressive disease with marked heterogeneity in outcome. Identifying patients at diagnosis at high risk of poor outcomes would allow treatment stratification. The most widely used definition of severe disease lacks discrimination with 85.2% of patients meeting the criteria for ‘disabling’ disease (Beaugerie et al. Gastroenterology 130: 650-656). A more discriminant composite severity score would benefit clinical research and aid clinical decision making. Methods: Based on a consensus of 5 clinicians, we designed a composite severity score, assessed over the 5 years after diagnosis, with a total possible score 1-16. The score was applied retrospectively in 367 CD patients who were also genotyped for 32 CD susceptibility loci. The severity score that would encompass the 50% of patients with the highest score was defined, and factors present at diagnosis both clinical and genetic - were assessed by the chi squared test for their ability to predict being in the more severe disease category. CD was classified according to the Montreal classification. Results: 367 CD patients (median age at Dx 30.8 (IQR 22.9-46.1)) were assessed. 249 patients had full data available for the first 5 years after diagnosis. The mean severity score was 6.3 (95% CI 5.9-6.6). Patients with a score >6 were defined as having more severe disease. Patients with more severe disease were younger at diagnosis (p=0.0004 for trend, odds ratio (OR) A1 v A2=4.42 (95% CI 1.4-13.9)) and had an ileal (p=0.0025, OR=2.2 (95% CI 1.32-3.68)) and upper GI location disease location at diagnosis (p=0.0008, OR=5.3 95% CI 1.9-14.7). Perianal disease at diagnosis approached but did not achieve statistical significance (p=0.052). Only rs9286879 (p=0.0085) and rs17582416 (p=0.0448) were observed more frequently in patients with severe disease. The need for steroids at diagnosis, having a first degree relative with IBD, needing surgery at diagnosis or smoking status at diagnosis did not differ between the groups. Conclusion: This index discriminates more effectively than existing definitions between severity groups. Disease location, age at diagnosis and genetic markers are associated with more severe disease but validation of these factors is needed in a separate cohort. Severity score (first 5 years after diagnosis)
BACKGROUND: An emergence of Crohn's disease has been reported in Asia over the past decade. While the natural history of Crohn's disease had been well described in Western series, data for Asian patients is scant. AIMS: We sought to assess the rate of intestinal complications and their associated risk factors in an Asian cohort. METHODS: This is a retrospective study of Crohn's disease patients currently on active follow-up at our centre. Records from the period 12/1975 to 11/2010 were evaluated . Medical records were reviewed and the clinical phenotypes at diagnosis of patients were categorized according to the Montreal classification. Baseline putative risk factors at and within 90 days of diagnosis such as age, sex, race, disease location and perianal disease were documented. The cumulative probabilities of developing intestinal stricturing and/or penetrating events were estimated using the Kaplan-Meier method and Cox proportional hazards regression was used to assess associations between baseline risk factors and progression to intestinal complication. RESULTS: The baseline clinical characteristics of 138 patients are as shown in Table 1. At baseline, 77.5% had nonstricturing nonpenetrating disease, 13.8% had stricturing disease, and 8.7% had penetrating disease. The cumulative risks of developing either complications were 22.5% (95% CI: 15.4-29.6) at or within 90 days, 29.4% (95% CI: 21.4-37.3) at 5 years, and 37.0% (95% CI: 27.7-46.3) at 10 years and 43.0% (95% CI: 31.2-54.7) at 20 years after diagnosis. Among 107 patients with nonstricturing, nonpenetrating disease at baseline, 17 were observed to experience a change in disease behavior after the first 90 days from diagnosis. The cumulative risks of developing either a stricturing or penetrating complication among those with nonstricturing nonpenetrating phenotype at diagnosis were 8.9% (95% CI: 2.9-14.9) at 5 years, 18.7% (95% CI: 9.4-28.1) at 10 years, and 26.5% (95% CI: 12.9-40.0) at 20 years. Among the 48 patients in the entire cohort with stricturing and penetrating phenotype, 32 (66.7%) underwent bowel resection surgery for management of Crohn's disease-related complications. None of the baseline risk factors were found to be significantly associated with the risk of intestinal complications. CONCLUSIONS: In this Asian tertiary study, 22.5% of patients with Crohn's disease experienced stricturing or penetrating complications within 90 days after diagnosis and 43% experienced intestinal complications 20 years after diagnosis. The complication rates observed resemble Western cohort studies. The surgical morbidities were substantial with 2 in 3 patients requiring bowel resection after a change in behavior. Predictive risk factors for complications will need to be confirmed in a larger Asian cohort.
Tu1269 New Insights Into the Genetic Basis for Variation in Crohn's Disease (CD) Phenotype in a Population-Based Study John D. Ryan, Mark S. Silverberg, Wei Xu, John R. Walker, Lesley A. Graff, Jason Ediger, Norine Miller, Linda Rogala, Michael Sargent, Rachel Carr, Joanne M. Stempak, Patricia E. Rawsthorne, Charles N. Bernstein Aims: In this study we evaluate for associations between clinical variables and IBD-related SNPs and specific disease phenotypes in a well-characterized, population-based CD cohort. Methods: Clinical data was obtained on a prospectively collected patient population from the Manitoba IBD Cohort Study (n=182, 112 females;70 males. These subjects were enrolled within 7 years of diagnosis (mean 4.3 yrs) and have been followed prsopectively every 6 months with surveys and annually with in-person interviews. Phenotyping and categorization of patients was performed using the Montreal Classification. DNA collected on these subjects was genotyped and the allele frequencies of known IBD-associated SNPs were determined. Analysis was performed to identify the SNPs associated with disease location and behaviour, surgical history, smoking status and psychological variables. Results presented are uncorrected. P value <0.01 was considered significant. Results: The distribution of patients within Montreal Classification categories was: A1=10%, A2=64%, A3=26%; L1=43%, L2=22%, L3= 34%, L4=7%; B1=45%, B2=33%, B3=22%, P=23%. Of the clinical variables, disease behaviour was strongly associated with surgery p <0.0001, OR=7.29) and smoking status (p=0.01, OR=2.09). Perianal disease was also associated with younger age at diagnosis (p=0.004). Subjects undergoing surgery tended to have higher childhood adversity impact p = 0.06, OR=1.81). Lifetime history of depression p = 0.07, OR=1.75) tended to be more common in patients with colonic involvement. For the genetic analysis, a SNP in DLG5 was associated with colonic and ileocolonic disease, while SNPs in RAC2 and NOX3 were associated with disease confined to the terminal ileum. SNPs in NR3C1, SCUBE3 and CDH19 were associated with disease behaviour. SNPs in TLR9, PARD3 and DLG5 were associated with perianal disease. 2 SNPs at the 5q31 locus and a SNP at SERPINA1 were associated with early surgery (< 3 years from diagnosis as opposed to no surgery) whereas one SNP in NOX4 was associated with no surgical intervention. Conclusions: Psychosocial variables were associated with colonic disease and early surgery but require further exploration in a larger sample size. Early surgery occurs in those harboring mutations at the 5q31 locus and at a SNP at SERPINA1 Disease location and behaviour was associated with a number of SNPs, some previously not reported.
Tu1271 Determinants Contributing to Fatigue in IBD Patients Lauran Vogelaar, Adriaan van 't Spijker, Ernst J. Kuipers, Christien J. van der Woude Background: Inflammatory bowel disease (IBD) patients (pts) suffer from a disabling disease which negatively influences their quality of life. Fatigue is a common symptom in IBD pts and contributes to this decreased quality of life. Aim: To assess underlying factors contributing to fatigue in IBD pts. Patients and methods: Group A included an adult IBD patient group that anonymously completed an online survey on fatigue. A second group included patients from the IBD-outpatient clinic, these patients filled out a paper version of this survey (group B). The survey included the Checklist Individual Strength (CIS) (fatigue: CIS score ≥ 35; non-fatigue CIS score < 35), the Hospital Anxiety and Depression Scale (HADS), the HarveyBradshaw Index and the Ulcerative Colitis Index for disease activity and information on current medication use. For statistical analysis descriptive statistics, univariate and multivariate logistic regression were used. Results: In total 977 pts were included. In group A 432 pts completed the survey (75% female, 57.9% Crohn's disease (CD), 42.1% ulcerative colitis (UC), mean age 40 (SD 12.6). The mean CIS score was 46 (range 13-56). Overall, 90.7% of the patients experienced fatigue. In group A 54 pts (12.5%) had a clinical depression and 99 pts (22.9%) with clinical anxiety. In contrast to non-fatigue pts, CD pts suffering from fatigue were significantly more depressive (OR 1.57; 95% CI 1.22-2.01), and had disease activity (OR 1.30; 95% CI 1.07-1.59). The results were similar in UC, however
S-783
AGA Abstracts
AGA Abstracts
Tu1268