1
with a CT scan within 24 hours of arrival. The average number of CTs was 2.5 with a range of 1-31. New/worse inflammation was found in 43.8% of CTs while any new/worse finding was found in 57.4%. PA+ occurred in 16.8% of CTs. Univariate analysis shows that younger and female patients were less likely to have I but not PA+. Steroid use did predict a higher probability of PA+ (OR 1.58, 95%CI 1.01-2.47) but not I (OR 1.01, 95%CI 0.70-1.44). Biologic agents and other immunosuppression did not predict either outcome. Among the labs, CRP was a good predictor of I and PA+ while ESR only predicted PA+. Higher absolute neutrophil count and lymphocyte count predicted both outcomes. The multivariable model for I had a c statistic of 0.68; a cutoff of 16% has a sensitivity of 99.6% and negative predictive value of 92.3%. The model for PA+ had better performance characteristics with a c statistic of 0.80; a cutoff of 5% has a sensitivity of 94.9% and a negative predictive value of 97.7%. Conclusions: Patients with CD are exposed to radiation frequently but have significant new/worse findings less than 60% of the time. Models with good negative predic- tive values predicting I and PA+ were identified. Automated use of these models could aid ER physicians in the decision to avoid CT scans in patients with low likelihood of a positive scan. Prospective studies are needed to validate these models and their utility in clinical practice. Tu1134 Layered Pattern of Enhancement and Retrodilation At Magnetic Resonance Enterography Predict the Outcome of Anti-TNF Alpha Therapy in Patients With Moderate-to-Severe Ileal Crohn's Disease Maria Laura Annunziata, Paola Balestrieri, Ilaria Sansoni, Chiara Coluccio, Riccardo Del Vescovo, Alessandro Tullio, Bruno Beomonte Zobel, Alessandro Armuzzi, Michele Cicala BACKGROUND Monoclonal antibodies targeting tumor necrosis factor (TNF-alpha) have proven to be highly effective in the management of moderate to severe Crohn's disease (CD), although the costs and side-effects still represent the major concerns. Magnetic Resonance Enterography (MRE) is a non-invasive technique which avoids ionizing radiation and demon- strates to correlate with clinical disease activity. Aim of the present study was to prospectively evaluate the accuracy of MRE parameters in predicting the clinical outcome of treatment with Infliximab (IFX) or Adalimumab (ADA) in active ileal CD patients. METHODS From January 2009 to May 2012, 31 patients with moderate-to-severe active ileal CD (mean age 44 yrs; M 14) were enrolled. Of these, 20 patients were treated with IFX and 11 with ADA with scheduled induction and maintenance. All patients, before and after 54 weeks of therapy, underwent MRE with oral administration of 1.5L of Polietilenglicol solution and ileocolonoscopy being classified according to the Simple Endoscopic Score for Crohn's Disease (SES-CD). Clinical activity was measured by the Harvey Bradshaw Index (HBI) and C-reactive protein (CRP). A specialized radiologist analyzed MRE images in T2-weighted and pre- and post-contrast-enhanced T1-weighted sequences. Wall thickness (WT), T2- ratio mural signal intensity (SI), T1-ratio Relative Contrast Enhancement (RCE), layered or homogenous Pattern of Enhancement (PE) and presence of retrodilation were assessed. WT, T2-ratio mural SI and T1-ratio RCE are expressed as mean and 95% confidence interval (CI). PE and the presence of retrodilation are expressed as Odds Ratio values. RESULTS WT, layered PE and mural T2-ratio SI correlated with HBI, CRP and endoscopic parameters as reported in table. 17 patients were classified as responders and 14 non responders as they presented an increase of HBI 3 or CRP5 or sub-score SES-CD5 or occlusive symptoms requiring surgery or endoscopic dilatation. Mean IS-T2 and WT values before therapy were significantly higher than those observed after therapy (20.3±4.1 vs 12.3±1.7, p ,0.01 and 8.6±1.3 vs 6.9±0.9, p,0.05, respectively). RCE values didn't differ before and after therapy. Presence of a layered PE as well as of retrodilatation was significantly associated with failure of biological therapy (OR, 95%CI) (4.52, 0.70-29.3 and 2.19, 0.95-5.03, respectively). CONCLUSIONS MRE is confirmed to be a non-invasive, useful, tool to monitor the disease course. Of the MRE parameters, layered PE and retrodilatation demonstrate to be reliable in predicting clinical outcome of anti-TNF alpha therapy in patients with moderate-to-severe ileal CD. *p,0.05 Tu1135 Serum Adalimumab and Immunogenicity in IBD Patients After 80mg Biweekly Maintenance Therapy Ofer Ben-Bassat, Scott Hauenstein, Anna Iacono, Sue P. Irwin, Sharat Singh, Gordon R. Greenberg Background/Aims: Adalimumab (ADA) is effective therapy for Crohn's disease (CD) and ulcerative colitis (UC) but maintenance dose escalation from biweekly to more frequent weekly injections may be a requirement to sustain clinical benefit. A more patient-convenient approach of biweekly 80mg therapy would be an advantage. However, this strategy could be associated with lower trough ADA levels and a higher rate of immunogenicity (ATA) with loss of response. We evaluated the relationship between serum ADA and ATA formation to clinical outcome in inflammatory bowel disease (IBD) patients after dose escalation to 80mg every other week(EOW) compared with 40mg every week (EW) using a fluid phase assay that simultaneously detects drug and ATI. Methods: A cohort of 57 IBD patients (48 CD; 9 UC) were treated with ADA induction followed by maintenance with no escalation of 40mg EOW (n=13) and dose-escalation to 40mg EW (n= 12) or 80mg EOW (n=32). Rates of steroid-free clinical remission (Harvey-Bradshaw Index 2) and normalization of CRP (, 5ug/L) were assessed in relation to the presence or absence of detectable serum levels of ADA with or without ATA formation. Serial serum samples were drawn prior to or at mid-interval of maintenance therapy and concentrations of ADA and ATA measured S-771 AGA Abstracts by an HPLC-based fluid phase assay (Prometheus Laboratories, San Diego CA). Results: After a median follow-up of 20.8 months (IQR: 17.1-28.7), rates of steroid-free remission for 80mg EOW compared with 40mg EW (75.1% vs.66.6%) were not different (P=0.81) and similar to patients treated with non-escalated 40mg EOW (69.2%). Median serum ADA for 80mg EOW compared with 40mg EW was not different (20.2 ug/ml vs.19.1 ug/ml) and tended to be higher than 40mg EOW (12.5 ug/ml). ATA formation for the cohort was 14% and was similar in the 3 groups: 80mg EOW (12.5%), 40mg EW (16.6%), 40mg EOW (15.3%). Median serum ADA for patients in remission (23.8 ug/ml; IQR: 13.1-27.4) was higher than for treatment failures (4.9 ug/ml; IQR: 0.8-10.1) (P ,0.001). The median serum ADA for patients with a CRP ,5 compared with CRP .5 was also higher (22.9ug/ml vs.10.5ug/ml) (P,0.001).Treatment failures had a higher rate of ATA formation (62.5%) and a lower median serum ADA (4.2 ug/ml; IQR: 0.8-10.3) independent of dose/interval. Conclusions: For patients requiring ADA dose escalation maintenance therapy 80mg biweekly was as effective as 40mg weekly with similar serum ADA levels and rates of immunogenicity. Treatment failure was associated with lower serum ADA levels with or without ATA formation and was independent of the dose or interval of maintenance treatment. Tu1136 Colectomy Rates for Medically-Refractory Ulcerative Colitis Have Declined in Parallel With Increasing Anti-TNF Use Krista Reich, Richard N. Fedorak, Karen J. Goodman, Haili Wang, Levinus A. Dieleman, Karen I. Kroeker Background: Ulcerative colitis (UC) can be treated by surgical removal of the large intestine. Surgery, however, can be deemed less attractive than other options due to the potential complications, risk of permanent ostomy, and the overall impact on patients' quality of life. Medical therapy remains the mainstay treatment for UC, with surgery reserved for medically- refractory disease, adverse events or risk of malignancy. The advent of cyclosporine and anti-TNF therapy in the UC algorithm for medically-refractory disease has extended medical management options. Aim: The primary objective of this study was to determine if colectomy rates for medically-refractory UC have changed since the introduction of cyclosporine and anti-TNF therapy. The secondary objective was to compare differences in characteristics of patients who underwent an emergent versus an elective colectomy. Methods: The Edmonton area health database was used to identify adults who were admitted to any of the four major hospitals with a diagnosis of UC and who underwent a colectomy between January 1, 1998 and December 31, 2011 for medically-refractory disease. The total population of UC cases in the Edmonton area was estimated for each calendar year by multiplying the total number of UC cases in Alberta by the proportion of the Alberta population residing in the Edmonton area during the corresponding year. The frequency of colectomy is presented as the percent per year having colectomy among UC patients. Results: There were 535 colectomies over the study period. The colectomy rate was 1.7%/year (95% CI: 1.0, 2.6) in 1998, peaked in 2002 (3.1%/year, 95% CI: 2.3, 4.1), and then declined over a 9 year period to 1.3%/year (95% CI: 0.1, 1.8) in 2011 (Figure 1). In 1998, the colectomy rate was low alongside the frequent use of cyclosporine. From 1998-2002, the colectomy rate increased, paralleling the decline in cyclosporine use. Subsequently, the decline in colectomy rate after 2002 paralleled the introduction and utilization of anti-TNF therapy. UC patients who underwent colectomy were further explored by stratifying on emergent or elective indication. UC patients who underwent an emergent colectomy had shorter duration of disease (4.9 vs. 9.6 years, p,0.001), were more likely to undergo surgery for medically-refractory disease (98% vs. 83%, p,0.001), and had a longer median length of stay in hospital (18 vs. 8 days, p ,0.001). Conclusion: The rate of colectomy for medically-refractory UC has declined since 2002, and this decline parallels the increase of anti-TNF use in this population. Patients undergoing emergent colectomy have a shorter duration of disease and a longer median length of stay in hospital. Figure 1. The colectomy rate shows a decreasing trend since 2002 Tu1137 Hemophagocytic Syndrome During Inflammatory Bowel Disease (IBD): A Serious and Unfamiliar Complication of Immunosuppressive Therapy Carmen Stefanescu, Matthieu Allez, Guillaume Cadiot, Mathurin Fumery, Aurelien Amiot, David Laharie, Guillaume Savoye, Jean-Marc Gornet, Philippe Seksik, Xavier Treton, Henri Duboc, Eric Fort, Coralie Bloch-Queyrat, Yoram Bouhnik Rational and purpose: Hemophagocytic syndrome (HLH), a rare disease characterized by inappropriate activation of macrophages resulting in phagocytosis of all bone marrow derived cells, mainly occurs in immunocompromised hosts. IBD patients treated with immunosup- pressive drugs have an increased risk to develop HLH. The aim of our study was to describe the characteristics of patients with IBD associated with HLH and determine the prognosis. Patients and methods: retrospective multicenter study conducted by the GETAID. Results: Between 2003 and 2012, 10/43 GETAID centers identified 27 patients (8 M/19 F). The mean age at diagnosis of HLH was 35 years (range 19-61). Twenty-four patients were followed for Crohn's disease, two for ulcerative colitis and one for indeterminate colitis. AGA Abstracts

Tu1136 Colectomy Rates for Medically-Refractory Ulcerative Colitis Have Declined in Parallel With Increasing Anti-TNF Use

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Page 1: Tu1136 Colectomy Rates for Medically-Refractory Ulcerative Colitis Have Declined in Parallel With Increasing Anti-TNF Use

with a CT scan within 24 hours of arrival. The average number of CTs was 2.5 with a rangeof 1-31. New/worse inflammation was found in 43.8% of CTs while any new/worse findingwas found in 57.4%. PA+ occurred in 16.8% of CTs. Univariate analysis shows that youngerand female patients were less likely to have I but not PA+. Steroid use did predict a higherprobability of PA+ (OR 1.58, 95%CI 1.01-2.47) but not I (OR 1.01, 95%CI 0.70-1.44).Biologic agents and other immunosuppression did not predict either outcome. Among thelabs, CRP was a good predictor of I and PA+ while ESR only predicted PA+. Higher absoluteneutrophil count and lymphocyte count predicted both outcomes. The multivariable modelfor I had a c statistic of 0.68; a cutoff of 16% has a sensitivity of 99.6% and negativepredictive value of 92.3%. The model for PA+ had better performance characteristics witha c statistic of 0.80; a cutoff of 5% has a sensitivity of 94.9% and a negative predictive valueof 97.7%. Conclusions: Patients with CD are exposed to radiation frequently but havesignificant new/worse findings less than 60% of the time. Models with good negative predic-tive values predicting I and PA+ were identified. Automated use of these models could aidER physicians in the decision to avoid CT scans in patients with low likelihood of apositive scan. Prospective studies are needed to validate these models and their utility inclinical practice.

Tu1134

Layered Pattern of Enhancement and Retrodilation At Magnetic ResonanceEnterography Predict the Outcome of Anti-TNF Alpha Therapy in PatientsWith Moderate-to-Severe Ileal Crohn's DiseaseMaria Laura Annunziata, Paola Balestrieri, Ilaria Sansoni, Chiara Coluccio, Riccardo DelVescovo, Alessandro Tullio, Bruno Beomonte Zobel, Alessandro Armuzzi, Michele Cicala

BACKGROUND Monoclonal antibodies targeting tumor necrosis factor (TNF-alpha) haveproven to be highly effective in the management of moderate to severe Crohn's disease (CD),although the costs and side-effects still represent the major concerns. Magnetic ResonanceEnterography (MRE) is a non-invasive technique which avoids ionizing radiation and demon-strates to correlate with clinical disease activity. Aim of the present study was to prospectivelyevaluate the accuracy of MRE parameters in predicting the clinical outcome of treatmentwith Infliximab (IFX) or Adalimumab (ADA) in active ileal CD patients. METHODS FromJanuary 2009 to May 2012, 31 patients with moderate-to-severe active ileal CD (mean age44 yrs; M 14) were enrolled. Of these, 20 patients were treated with IFX and 11 with ADAwith scheduled induction and maintenance. All patients, before and after 54 weeks oftherapy, underwent MRE with oral administration of 1.5L of Polietilenglicol solution andileocolonoscopy being classified according to the Simple Endoscopic Score for Crohn'sDisease (SES-CD). Clinical activity was measured by the Harvey Bradshaw Index (HBI) andC-reactive protein (CRP). A specialized radiologist analyzed MRE images in T2-weightedand pre- and post-contrast-enhanced T1-weighted sequences. Wall thickness (WT), T2-ratio mural signal intensity (SI), T1-ratio Relative Contrast Enhancement (RCE), layered orhomogenous Pattern of Enhancement (PE) and presence of retrodilation were assessed. WT,T2-ratio mural SI and T1-ratio RCE are expressed as mean and 95% confidence interval(CI). PE and the presence of retrodilation are expressed as Odds Ratio values. RESULTSWT, layered PE and mural T2-ratio SI correlated with HBI, CRP and endoscopic parametersas reported in table. 17 patients were classified as responders and 14 non responders asthey presented an increase of HBI≥3 or CRP≥5 or sub-score SES-CD≥5 or occlusive symptomsrequiring surgery or endoscopic dilatation. Mean IS-T2 and WT values before therapy weresignificantly higher than those observed after therapy (20.3±4.1 vs 12.3±1.7, p ,0.01 and8.6±1.3 vs 6.9±0.9, p,0.05, respectively). RCE values didn't differ before and after therapy.Presence of a layered PE as well as of retrodilatation was significantly associated with failureof biological therapy (OR, 95%CI) (4.52, 0.70-29.3 and 2.19, 0.95-5.03, respectively).CONCLUSIONS MRE is confirmed to be a non-invasive, useful, tool to monitor the diseasecourse. Of the MRE parameters, layered PE and retrodilatation demonstrate to be reliablein predicting clinical outcome of anti-TNF alpha therapy in patients with moderate-to-severeileal CD.

* p,0.05

Tu1135

Serum Adalimumab and Immunogenicity in IBD Patients After 80mg BiweeklyMaintenance TherapyOfer Ben-Bassat, Scott Hauenstein, Anna Iacono, Sue P. Irwin, Sharat Singh, Gordon R.Greenberg

Background/Aims: Adalimumab (ADA) is effective therapy for Crohn's disease (CD) andulcerative colitis (UC) but maintenance dose escalation from biweekly to more frequentweekly injections may be a requirement to sustain clinical benefit. A more patient-convenientapproach of biweekly 80mg therapy would be an advantage. However, this strategy couldbe associated with lower trough ADA levels and a higher rate of immunogenicity (ATA)with loss of response. We evaluated the relationship between serum ADA and ATA formationto clinical outcome in inflammatory bowel disease (IBD) patients after dose escalation to80mg every other week(EOW) compared with 40mg every week (EW) using a fluid phaseassay that simultaneously detects drug and ATI. Methods: A cohort of 57 IBD patients (48CD; 9 UC) were treated with ADA induction followed by maintenance with no escalationof 40mg EOW (n=13) and dose-escalation to 40mg EW (n= 12) or 80mg EOW (n=32).Rates of steroid-free clinical remission (Harvey-Bradshaw Index ≤ 2) and normalization ofCRP (, 5ug/L) were assessed in relation to the presence or absence of detectable serumlevels of ADA with or without ATA formation. Serial serum samples were drawn prior toor at mid-interval of maintenance therapy and concentrations of ADA and ATA measured

S-771 AGA Abstracts

by an HPLC-based fluid phase assay (Prometheus Laboratories, San Diego CA). Results:After a median follow-up of 20.8 months (IQR: 17.1-28.7), rates of steroid-free remissionfor 80mg EOW compared with 40mg EW (75.1% vs.66.6%) were not different (P=0.81)and similar to patients treated with non-escalated 40mg EOW (69.2%). Median serum ADAfor 80mg EOW compared with 40mg EW was not different (20.2 ug/ml vs.19.1 ug/ml) andtended to be higher than 40mg EOW (12.5 ug/ml). ATA formation for the cohort was 14%and was similar in the 3 groups: 80mg EOW (12.5%), 40mg EW (16.6%), 40mg EOW(15.3%). Median serum ADA for patients in remission (23.8 ug/ml; IQR: 13.1-27.4) washigher than for treatment failures (4.9 ug/ml; IQR: 0.8-10.1) (P,0.001). The median serumADA for patients with a CRP ,5 compared with CRP.5 was also higher (22.9ug/mlvs.10.5ug/ml) (P,0.001).Treatment failures had a higher rate of ATA formation (62.5%)and a lower median serum ADA (4.2 ug/ml; IQR: 0.8-10.3) independent of dose/interval.Conclusions: For patients requiring ADA dose escalationmaintenance therapy 80mg biweeklywas as effective as 40mg weekly with similar serum ADA levels and rates of immunogenicity.Treatment failure was associated with lower serum ADA levels with or without ATA formationand was independent of the dose or interval of maintenance treatment.

Tu1136

Colectomy Rates for Medically-Refractory Ulcerative Colitis Have Declined inParallel With Increasing Anti-TNF UseKrista Reich, Richard N. Fedorak, Karen J. Goodman, Haili Wang, Levinus A. Dieleman,Karen I. Kroeker

Background: Ulcerative colitis (UC) can be treated by surgical removal of the large intestine.Surgery, however, can be deemed less attractive than other options due to the potentialcomplications, risk of permanent ostomy, and the overall impact on patients' quality of life.Medical therapy remains the mainstay treatment for UC, with surgery reserved for medically-refractory disease, adverse events or risk of malignancy. The advent of cyclosporine andanti-TNF therapy in the UC algorithm for medically-refractory disease has extended medicalmanagement options. Aim: The primary objective of this study was to determine if colectomyrates for medically-refractory UC have changed since the introduction of cyclosporine andanti-TNF therapy. The secondary objective was to compare differences in characteristics ofpatients who underwent an emergent versus an elective colectomy. Methods: The Edmontonarea health database was used to identify adults who were admitted to any of the four majorhospitals with a diagnosis of UC and who underwent a colectomy between January 1, 1998and December 31, 2011 for medically-refractory disease. The total population of UC casesin the Edmonton area was estimated for each calendar year by multiplying the total numberof UC cases in Alberta by the proportion of the Alberta population residing in the Edmontonarea during the corresponding year. The frequency of colectomy is presented as the percentper year having colectomy among UC patients. Results: There were 535 colectomies overthe study period. The colectomy rate was 1.7%/year (95% CI: 1.0, 2.6) in 1998, peaked in2002 (3.1%/year, 95% CI: 2.3, 4.1), and then declined over a 9 year period to 1.3%/year(95% CI: 0.1, 1.8) in 2011 (Figure 1). In 1998, the colectomy rate was low alongside thefrequent use of cyclosporine. From 1998-2002, the colectomy rate increased, parallelingthe decline in cyclosporine use. Subsequently, the decline in colectomy rate after 2002paralleled the introduction and utilization of anti-TNF therapy. UC patients who underwentcolectomywere further explored by stratifying on emergent or elective indication. UC patientswho underwent an emergent colectomy had shorter duration of disease (4.9 vs. 9.6 years,p,0.001), were more likely to undergo surgery for medically-refractory disease (98% vs.83%, p,0.001), and had a longer median length of stay in hospital (18 vs. 8 days, p ,0.001).Conclusion: The rate of colectomy for medically-refractory UC has declined since 2002,and this decline parallels the increase of anti-TNF use in this population. Patients undergoingemergent colectomy have a shorter duration of disease and a longer median length of stayin hospital.

Figure 1. The colectomy rate shows a decreasing trend since 2002

Tu1137

Hemophagocytic Syndrome During Inflammatory Bowel Disease (IBD): ASerious and Unfamiliar Complication of Immunosuppressive TherapyCarmen Stefanescu, Matthieu Allez, Guillaume Cadiot, Mathurin Fumery, Aurelien Amiot,David Laharie, Guillaume Savoye, Jean-Marc Gornet, Philippe Seksik, Xavier Treton,Henri Duboc, Eric Fort, Coralie Bloch-Queyrat, Yoram Bouhnik

Rational and purpose: Hemophagocytic syndrome (HLH), a rare disease characterized byinappropriate activation of macrophages resulting in phagocytosis of all bone marrow derivedcells, mainly occurs in immunocompromised hosts. IBD patients treated with immunosup-pressive drugs have an increased risk to develop HLH. The aim of our study was to describethe characteristics of patients with IBD associated with HLH and determine the prognosis.Patients and methods: retrospective multicenter study conducted by the GETAID. Results:Between 2003 and 2012, 10/43 GETAID centers identified 27 patients (8 M/19 F). Themean age at diagnosis of HLH was 35 years (range 19-61). Twenty-four patients werefollowed for Crohn's disease, two for ulcerative colitis and one for indeterminate colitis.

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