Introduction: There is increasing emphasis on patient reported outcomes and quality of life (QOL) measures in assessment of patients with Crohn's disease (CD). Descriptive QOL measures often require time-consuming questionnaires comprised of multiple QOL domains. Utility assessment is an attractive alternative measure because it provides a single global measure of overall QOL. The paper standard gamble (PSG) is a 1-page questionnaire in which patients are offered a hypothetical pill that confers a specific risk of either perfect health or death and has been shown to be a simple and reliable measure of patient utility. In this study we compared patients in different CD health states with respect to their generic health measure (EQ5D), health rating (EQ5D visual analog scale (VAS)), and utility (PSG). Methods: We prospectively surveyed adults with CD seen for outpatient gastroenterology clinic evaluation. Patients provided informed consent and filled out both the EQ5D and PSG. A gastroenterologist blinded to questionnaire results reviewed the clinic visit and classified the patient's health state based on symptoms (symptomatic or asymptomatic) and objective assessment (active disease, inactive disease, or no testing if none had been done within 6 months of the clinic visit). Results: 219 CD patients (mean age 41.9 years; range 18-77) were recruited. Disease duration was 16.5 + 12.9 years and 57% had prior CD abdominal surgery. The EQ5D index score, EQ5D VAS and the PSG all differentiated between asymptomatic and symptomatic patients but did not differentiate between inactive and active disease states (Tables 1 and 2). When comparing the most extreme of the four health states, asymptomatic inactive (“remission”) versus the symptomatic active groups, all 3 scales differentiated between states (Table 3). The Spearman rank correlation between the utility and other measures was weak. Conclusion: While symptomatic patients had lower health ratings and generic health measures, their utilities were not significantly different from asymptomatic patients. Disease activity was not associated with changes in any measure. Symptomatic patients with objective active inflammation appear willing to take a 7.3% greater risk of death in exchange for perfect health compared to patients with no symptoms and no active disease. Given the limited correlation between utility and other measures, the PSG, a simple one question utility, can be an important tool for clinical trials and QOL studies.689_A Figure 1. Correlation of symptoms and disease activity with EQ5D and PSG689_B Figure 2. Comparison of asymptomatic inactive patients to symptomatic active patients
Purpose: Ileal-pouch anal anastomosis (IPAA) is the surgical treatment of choice for patients with ulcerative colitis (UC) and indeterminate colitis who require surgery. A subsequent change in diagnosis to Crohn's disease (CD) involving the IPAA is an uncommon but increasingly recognized complication of this surgery and can be associated with risk of pouch loss. Based on increasing knowledge of genetic susceptibility in CD and UC, our aim was to determine if genetic factors are associated with risk of being diagnosed with CD of IPAA. Methods: A total of 837 subjects from a DNA bank met inclusion criteria: 97 subjects with CD of IPAA, 470 with “typical” CD and 270 with UC. CD of IPAA was diagnosed on the basis of one or more of the following: 1) colectomy pathology consistent with CD, 2) evidence of ulcers or strictures in the ileum proximal to the pouch in the absence of NSAID use, 3) development of perianal or abdominal fistulizing disease more than 1 year after IPAA surgery. Genotyping for single nucleotide polymorphisms (SNPs) in NOD2 (SNPs 8, 12 and 13), ATG16L1, IRGM, IL23R, and PTPN2 was performed using TaqMan assays. Results: There were baseline differences between the three groups with UC subjects having a higher proportion of male gender, a lower rate of current smoking, and a lower rate of family history of IBD (Table 1). Differences in variant allele frequency across the 3 groups were seen for IL23R, ATG16L1 and NOD2 SNPs but ATG16L1 appeared to best distinguish CD of IPAA from UC subjects. Multivariable baseline-category logit regression analysis was performed to assess associations between ATG16L1, smoking history and family history with CD of IPAA disease status versus UC and CD separately. The ATG16L1 G allele variant (OR = 1.4; P = 0.05) and current smoking (OR = 6.8; P < 0.001) were associated with increased risk of CD of IPAA compared to UC whereas no differences were seen between CD of IPAA versus CD. For each ATG16L1 G allele, subjects were 40% more likely to have CD of IPAA versus UC after adjusting for smoking and family history.Table 1: Demographic features and genotype resultsConclusion: The ATG16L1 variant is associated with increased risk of CD of IPAA. However, since this variant also occurs commonly in UC, its use in predicting subsequent diagnosis of CD at time of surgery for UC is limited. Current smoking, a modifiable risk factor, is strongly associated with CD of IPAA.Table 2: Logistic regression model: Crohn's of the Pouch vs, ulcerative colitis
