1
by Cohen's effect size, Guyatt's responsiveness measure, and area under the receiver-operating characteristic (ROC) curves. The strength of relationship was evaluated according to conven- tional thresholds whereby 0.2, 0.5, and 0.8 indicate small, moderate, and large degrees of responsiveness, respectively. 1 Results: Among 121 patients, 29 were clinically unchanged and 92 were changed (Table 1). Between weeks 0 and 6 or 10, the effect sizes and Guyatt's responsiveness statistics (95% confidence intervals [CIs]) based on mean scores for the MMCS, MBS, and UCEIS were 0.49 (0.28, 0.71), 0.49 (0.28, 0.71), and 0.58 (0.36, 0.81) and 0.32 (0.11, 0.53), 0.33 (0.12, 0.54), and 0.47 (0.25, 0.69), respectively. The corresponding estimates (95% CI) for the areas under the ROC curves were 0.66 (0.55, 0.78), 0.65 (0.54, 0.77), and 0.68 (0.58, 0.79) The ROC curves are displayed in Figure 1. Conclusion: Although the UCEIS had greater numerical values, the MMCS, MBS, and UCEIS displayed similar, small-to-moderate, responsiveness for the assessment of UC disease activity. These results have important implications for sample size in early drug development. References 1. Husted JA, Cook RJ, Farewell VT, Gladman DD. Methods for assessing responsiveness: a critical review and recommendations. J Clin Epidemiol. 2000 May;53(5):459-68. Table 1. Score changes between 0 and 6/10 weeks in clinically changed and unchanged groups Figure 1. ROC Curves for MMCS, MBS, and UCEIS Sa1197 Ulcerative Colitis Patients After Pouch Operation Are Serologically More Comparable to Crohn's Disease Patients Idan Goren, Lior Yahav, Hagit Tulchinsky, Iris Dotan BACKGROUND & AIMS: Pouchitis is the most frequent long-term complication of ulcerative colitis (UC) patients undergoing large bowel resection with the formation of an ileo-anal pouch from normal ileum. Antibodies against glycans comprising yeast cell wall components have been associated with Crohn's disease (CD). We hypothesized that pouchitis and pouch complications may be a form of inflammatory bowel disease (IBD) resembling CD and that the serologic status of pouch patients will be more comparable to CD, than to UC patients METHODS: Patients were prospectively recruited in a tertiary IBD center. Pouch patients' population was stratified according to disease behavior into normal pouch (NP), acute/ recurrent acute pouchitis (AP/RAP), and chronic pouchitis and Crohn's-like disease of the pouch (CP/CLDP). Anti-Saccharomyces cerevisiae antibodies (gASCA), antilaminaribioside , antichitobioside , and anti-mannobioside carbohydrate antibodies (ALCA, ACCA, and AMCA, respectively) were detected using ELISA (IBDX, Glycominds Ltd, Israel), and corre- lated with IBD type and disease behavior. pANCA was assessed using immunofluorescence. RESULTS: Five hundred and seven IBD patients: (253 (50%) CD, 124 (24.4%) UC and 130 UC-pouch (25.6%) patients were prospectively recruited. At least one positive anti-glycan antibody was detected in 77.5% CD, 33.1% UC, and 52.3% pouch patients (p<0.001) . Interestingly, ACCA and AMCA prevalence was significantly higher in pouch compared to UC patients: ACCA: 33.2%, 16.9%, and 25.4% (p=0.003) and AMCA: 35.6%, 7.3%, and 26.2% in CD, UC, and pouch patients, respectively (p <0.001) , while ALCA and ASCA prevalence was comparable. Longer time since pouch surgery to serologic assessment was associated with complicated pouch behavior: 8.3, 12.55 and 11.22 years for NP, AP/RAP, and CP/CLDP, respectively, p=0.01. However, no association between the prevalence or levels of a particular anti-glycan antibody and pouch behavior was found. Male gender was associated with higher prevalence of positive serological test with an OR of 1.9 (CI 1.28- 2.86, p<0.01) regardless of disease type. UC compared to pouch patients had an OR of 0.44 (CI 0.25-0.75) for having positive serologies . CONCLUSIONS: The prevalence of the CD-associated anti-glycan antibodies ACCA and AMCA is significantly increased in pouch compared to UC patients. The differential prevalence of ACCA and AMCA compared to ALCA and ASCA in pouch patients may suggest that pouch surgery triggers differential immune responses to glycans. Longer time since pouch surgery is significantly associated with pouch complications but not with increased serologies, suggesting that their development is an earlier event. Thus, UC patients after pouch operation are serologically more comparable to CD, supporting the notion that IBD is a spectrum rather than distinct diseases. Sa1198 Agreement Among Experts in the Endoscopic Evaluation of Postoperative Recurrence in Crohn's Disease Using the Rutgeerts Score Krisztina Gecse, M. Lowenberg, Peter Bossuyt, Paul J. Rutgeerts, Severine Vermeire, Larry Stitt, Margaret K. Vandervoort, William Sandborn, Brian G. Feagan, Mark A. Samaan, Reena Khanna, Elena Dubcenco, Barrett G. Levesque, Geert R. D'Haens BACKGROUND: The Rutgeerts score was developed to assess the endoscopic severity of post-operative Crohn's disease (CD) recurrence, however this instrument has not been fully validated. Furthermore, the i2 subscore has been a source of debate as it groups lesions at the anastomosis and in the neoterminal ileum into one category. We defined the intra- and S-227 AGA Abstracts inter-rater agreement for the Rutgeerts score and a modified Rutgeerts score which redefined the i2 subscore. METHODS: Four experienced central readers reviewed video recordings from colonoscopies obtained from 30 CD patients with a history of ileo-colonic resection. The mucosal appearances of the neo-terminal ileum, anastomosis, and proximal colon were evaluated using the Rutgeerts score. In addition, a modified Rutgeerts score which subdivided i2 lesions [i2a = lesions confined to the ileocolonic anastomosis (including anastomotic stenosis); i2b = lesions in the neoterminal ileum with normal intervening mucosa, Figure 1], and any additional observed lesions were recorded. Videos were triplicated and assessed, in random order, by each reader. The inter- and intra-rater agreement was determined by calculating the inter-class correlation coefficients (ICCs). To assess validity, the score was correlated to a global assessment of disease severity (GELS) based on a 10 cm linear analogue scale. RESULTS: The intra-rater ICCs for the Rutgeerts score, modified Rutgeerts, and GELS scores (95% CIs) were .81 (.72-.88), .83 (.75-.90), and .76 (.66-.86), respectively. The corresponding inter-rater agreement ICCs were .72 (.60-.83), .75 (.63-.85), and .62 (.47- .77), respectively. The correlation coefficient between the Rutgeerts and modified Rutgeerts scores with GELS was .80 (.65-.89), and .81 (.65-.90), respectively. CONCLUSION: These results indicate that central reading is reliable for the assessment of post-operative endoscopic CD disease activity. Further study is needed to assess the responsiveness of these endoscopic indices to changes in disease activity and to validate the modified Rutgeerts score both for clinical use and for prediction of the future outcome. Figure 1. Rutgeerts and Modified Rutgeerts scores Sa1199 Mucosal Healing in Ulcerative Colitis: Do Mayo 0 and 1 Scores Really Have the Same Prognostic Value? A Prospective Observational Cohort Study Manuel Barreiro-de Acosta, Nicolau vallejo-Senra, Daniel De la Iglesia Garcia, Laura Uribarri-González, Iria Baston-Rey, Rocio Ferreiro, Aurelio Lorenzo, Enrique Dominguez- Munoz Background and aim: Mucosal healing has become a common endpoint in most therapeutic trials and an important goal in the treatment of ulcerative colitis (UC) patients. Despite important differences between endoscopic Mayo sub-scores 0 and 1, most important trials consider both scores as mucosal healing. We hypothesized that only an endoscopic Mayo score of 0 should be defined as mucosal healing. The aim of this study is to evaluate the difference between endoscopic Mayo-0 and Mayo-1 in the clinical course of UC. Methods: A prospective observational cohort study was designed. All UC patients with demonstrated mucosal healing at colonoscopy were consecutively included and classified according to the Montreal Classification. Mucosal healing was defined as an endoscopic Mayo sub-score of 0 or 1. In order to avoid interpretation variability, all colonoscopies were performed and scored by the same endoscopist. Mayo-0 was defined as a normal or inactive disease and Mayo-1 as the presence of erythema, decreased vascular pattern or mild friability. Clinical relapse was defined as the need for remission induction treatment, any treatment escalation, hospitalization or colectomy. In order to assess the clinical course of UC, all clinical relapses were evaluated at months 6 and 12 after inclusion colonoscopy. The influence of demographic variables on the different Mayo subgroups in the clinical course of the disease was also evaluated. Results are shown as odds ratio (OR) and 95%CI and analyzed by the chi-squared test and multiple regression whenever appropriate. Results: 187 consecutive UC patients with mucosal healing [127 (67.9%) Mayo-0 and 60 (32.1%) Mayo-1] were included [94 male (50.3%), mean age 52 years, ages ranging from 22 to 85]. UC was classified as E1 in 31.3% of patients, E2 in 42.2%, and E3 in 26.5% according to the Montreal classification. 9.4% of patients with Mayo-0 and 36.6% with Mayo-1 presented a relapse during the first 6 months of follow-up (p<0.001). These differences in relapses were independent of the UC extension (E1 p=0.006, E2 p=0.002, E3 p=0.008). During the following 6 months (from 6 to 12 month) the number of patients who relapsed was similar in Mayo 0 and 1 scores (14.6%vs 16.6%, p=0.868), probably influenced by the therapy escalation in those who relapsed in the previous 6 months. The only factor independently associated with relapses in a multivariate analysis was a Mayo-1 endoscopic sub-score (OR=6.27, 95%CI 2.75-14.30, p<0.001). Conclusions: Patients with Mayo sub-score 1 presented a worse clinical course than those with Mayo sub-score 0, regardless of the extension of UC. This study demonstrated AGA Abstracts

Sa1198 Agreement Among Experts in the Endoscopic Evaluation of Postoperative Recurrence in Crohn's Disease Using the Rutgeerts Score

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by Cohen's effect size, Guyatt's responsiveness measure, and area under the receiver-operatingcharacteristic (ROC) curves. The strength of relationship was evaluated according to conven-tional thresholds whereby 0.2, 0.5, and 0.8 indicate small, moderate, and large degrees ofresponsiveness, respectively.1 Results: Among 121 patients, 29 were clinically unchangedand 92 were changed (Table 1). Between weeks 0 and 6 or 10, the effect sizes and Guyatt'sresponsiveness statistics (95% confidence intervals [CIs]) based on mean scores for theMMCS, MBS, and UCEIS were 0.49 (0.28, 0.71), 0.49 (0.28, 0.71), and 0.58 (0.36, 0.81) and0.32 (0.11, 0.53), 0.33 (0.12, 0.54), and 0.47 (0.25, 0.69), respectively. The correspondingestimates (95% CI) for the areas under the ROC curves were 0.66 (0.55, 0.78), 0.65 (0.54,0.77), and 0.68 (0.58, 0.79) The ROC curves are displayed in Figure 1. Conclusion: Althoughthe UCEIS had greater numerical values, the MMCS, MBS, and UCEIS displayed similar,small-to-moderate, responsiveness for the assessment of UC disease activity. These resultshave important implications for sample size in early drug development. References 1. HustedJA, Cook RJ, Farewell VT, Gladman DD. Methods for assessing responsiveness: a criticalreview and recommendations. J Clin Epidemiol. 2000 May;53(5):459-68.Table 1. Score changes between 0 and 6/10 weeks in clinically changed and unchanged groups

Figure 1. ROC Curves for MMCS, MBS, and UCEIS

Sa1197

Ulcerative Colitis Patients After Pouch Operation Are Serologically MoreComparable to Crohn's Disease PatientsIdan Goren, Lior Yahav, Hagit Tulchinsky, Iris Dotan

BACKGROUND & AIMS: Pouchitis is the most frequent long-term complication of ulcerativecolitis (UC) patients undergoing large bowel resection with the formation of an ileo-analpouch from normal ileum. Antibodies against glycans comprising yeast cell wall componentshave been associated with Crohn's disease (CD). We hypothesized that pouchitis and pouchcomplications may be a form of inflammatory bowel disease (IBD) resembling CD and thatthe serologic status of pouch patients will be more comparable to CD, than to UC patientsMETHODS: Patients were prospectively recruited in a tertiary IBD center. Pouch patients'population was stratified according to disease behavior into normal pouch (NP), acute/recurrent acute pouchitis (AP/RAP), and chronic pouchitis and Crohn's-like disease of thepouch (CP/CLDP). Anti-Saccharomyces cerevisiae antibodies (gASCA), antilaminaribioside, antichitobioside , and anti-mannobioside carbohydrate antibodies (ALCA, ACCA, andAMCA, respectively) were detected using ELISA (IBDX, Glycominds Ltd, Israel), and corre-lated with IBD type and disease behavior. pANCA was assessed using immunofluorescence.RESULTS: Five hundred and seven IBD patients: (253 (50%) CD, 124 (24.4%) UC and 130UC-pouch (25.6%) patients were prospectively recruited. At least one positive anti-glycanantibody was detected in 77.5% CD, 33.1% UC, and 52.3% pouch patients (p<0.001) .Interestingly, ACCA and AMCA prevalence was significantly higher in pouch compared toUC patients: ACCA: 33.2%, 16.9%, and 25.4% (p=0.003) and AMCA: 35.6%, 7.3%, and26.2% in CD, UC, and pouch patients, respectively (p <0.001) , while ALCA and ASCAprevalence was comparable. Longer time since pouch surgery to serologic assessment wasassociated with complicated pouch behavior: 8.3, 12.55 and 11.22 years for NP, AP/RAP,and CP/CLDP, respectively, p=0.01. However, no association between the prevalence orlevels of a particular anti-glycan antibody and pouch behavior was found. Male gender wasassociated with higher prevalence of positive serological test with an OR of 1.9 (CI 1.28-2.86, p<0.01) regardless of disease type. UC compared to pouch patients had an OR of0.44 (CI 0.25-0.75) for having positive serologies . CONCLUSIONS: The prevalence of theCD-associated anti-glycan antibodies ACCA and AMCA is significantly increased in pouchcompared to UC patients. The differential prevalence of ACCA and AMCA compared toALCA and ASCA in pouch patients may suggest that pouch surgery triggers differentialimmune responses to glycans. Longer time since pouch surgery is significantly associated withpouch complications but not with increased serologies, suggesting that their development isan earlier event. Thus, UC patients after pouch operation are serologically more comparableto CD, supporting the notion that IBD is a spectrum rather than distinct diseases.

Sa1198

Agreement Among Experts in the Endoscopic Evaluation of PostoperativeRecurrence in Crohn's Disease Using the Rutgeerts ScoreKrisztina Gecse, M. Lowenberg, Peter Bossuyt, Paul J. Rutgeerts, Severine Vermeire, LarryStitt, Margaret K. Vandervoort, William Sandborn, Brian G. Feagan, Mark A. Samaan,Reena Khanna, Elena Dubcenco, Barrett G. Levesque, Geert R. D'Haens

BACKGROUND: The Rutgeerts score was developed to assess the endoscopic severity ofpost-operative Crohn's disease (CD) recurrence, however this instrument has not been fullyvalidated. Furthermore, the i2 subscore has been a source of debate as it groups lesions atthe anastomosis and in the neoterminal ileum into one category. We defined the intra- and

S-227 AGA Abstracts

inter-rater agreement for the Rutgeerts score and a modified Rutgeerts score which redefinedthe i2 subscore. METHODS: Four experienced central readers reviewed video recordingsfrom colonoscopies obtained from 30 CD patients with a history of ileo-colonic resection.The mucosal appearances of the neo-terminal ileum, anastomosis, and proximal colon wereevaluated using the Rutgeerts score. In addition, a modified Rutgeerts score which subdividedi2 lesions [i2a = lesions confined to the ileocolonic anastomosis (including anastomoticstenosis); i2b = lesions in the neoterminal ileum with normal intervening mucosa, Figure1], and any additional observed lesions were recorded. Videos were triplicated and assessed,in random order, by each reader. The inter- and intra-rater agreement was determined bycalculating the inter-class correlation coefficients (ICCs). To assess validity, the score wascorrelated to a global assessment of disease severity (GELS) based on a 10 cm linear analoguescale. RESULTS: The intra-rater ICCs for the Rutgeerts score, modified Rutgeerts, and GELSscores (95% CIs) were .81 (.72-.88), .83 (.75-.90), and .76 (.66-.86), respectively. Thecorresponding inter-rater agreement ICCs were .72 (.60-.83), .75 (.63-.85), and .62 (.47-.77), respectively. The correlation coefficient between the Rutgeerts and modified Rutgeertsscores with GELS was .80 (.65-.89), and .81 (.65-.90), respectively. CONCLUSION: Theseresults indicate that central reading is reliable for the assessment of post-operative endoscopicCD disease activity. Further study is needed to assess the responsiveness of these endoscopicindices to changes in disease activity and to validate the modified Rutgeerts score both forclinical use and for prediction of the future outcome.

Figure 1. Rutgeerts and Modified Rutgeerts scores

Sa1199

Mucosal Healing in Ulcerative Colitis: Do Mayo 0 and 1 Scores Really Havethe Same Prognostic Value? A Prospective Observational Cohort StudyManuel Barreiro-de Acosta, Nicolau vallejo-Senra, Daniel De la Iglesia Garcia, LauraUribarri-González, Iria Baston-Rey, Rocio Ferreiro, Aurelio Lorenzo, Enrique Dominguez-Munoz

Background and aim: Mucosal healing has become a common endpoint in most therapeutictrials and an important goal in the treatment of ulcerative colitis (UC) patients. Despiteimportant differences between endoscopic Mayo sub-scores 0 and 1, most important trialsconsider both scores as mucosal healing. We hypothesized that only an endoscopic Mayoscore of 0 should be defined as mucosal healing. The aim of this study is to evaluate thedifference between endoscopic Mayo-0 and Mayo-1 in the clinical course of UC. Methods:A prospective observational cohort study was designed. All UC patients with demonstratedmucosal healing at colonoscopy were consecutively included and classified according to theMontreal Classification. Mucosal healing was defined as an endoscopic Mayo sub-score of0 or 1. In order to avoid interpretation variability, all colonoscopies were performed andscored by the same endoscopist. Mayo-0 was defined as a normal or inactive disease andMayo-1 as the presence of erythema, decreased vascular pattern or mild friability. Clinicalrelapse was defined as the need for remission induction treatment, any treatment escalation,hospitalization or colectomy. In order to assess the clinical course of UC, all clinical relapseswere evaluated at months 6 and 12 after inclusion colonoscopy. The influence of demographicvariables on the different Mayo subgroups in the clinical course of the disease was alsoevaluated. Results are shown as odds ratio (OR) and 95%CI and analyzed by the chi-squaredtest and multiple regression whenever appropriate. Results: 187 consecutive UC patientswith mucosal healing [127 (67.9%) Mayo-0 and 60 (32.1%) Mayo-1] were included [94male (50.3%), mean age 52 years, ages ranging from 22 to 85]. UC was classified as E1 in31.3% of patients, E2 in 42.2%, and E3 in 26.5% according to the Montreal classification.9.4% of patients with Mayo-0 and 36.6% with Mayo-1 presented a relapse during the first6 months of follow-up (p<0.001). These differences in relapses were independent of theUC extension (E1 p=0.006, E2 p=0.002, E3 p=0.008). During the following 6 months (from6 to 12 month) the number of patients who relapsed was similar in Mayo 0 and 1 scores(14.6%vs 16.6%, p=0.868), probably influenced by the therapy escalation in those whorelapsed in the previous 6 months. The only factor independently associated with relapsesin a multivariate analysis was a Mayo-1 endoscopic sub-score (OR=6.27, 95%CI 2.75-14.30,p<0.001). Conclusions: Patients with Mayo sub-score 1 presented a worse clinical coursethan those with Mayo sub-score 0, regardless of the extension of UC. This study demonstrated

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