UCS Duration Research Articles

P503 Differentiation of patients with IBD at increased risk of CRC using UR-CARE: A Single Centre Experience

Abstract Background The United Registries for Clinical Assessment and Research (UR-CARE) platform aims to facilitate and improve the daily clinical care of patients with Inflammatory Bowel Disease (IBD). The possibility of updating the medical data in UR-CARE at each patient visit allows for strict follow-up and enables the doctor to draw relevant recommendations. The study is aimed at identifying registered IBD patients at increased risk of colorectal cancer (CRC) via UR-CARE. Methods Outpatients and inpatients with a confirmed IBD diagnosis, who had signed informed consent, were entered with their clinical data in UR-CARE to the centre UMHAT “Tsaritsa Yoanna-ISUL”. Only the statistical and filter opportunities of the digital platform were used. The study was conducted with our own data from our centre database. Results 274 IBD patients (120 with ulcerative colitis [UC], 144 with Crohn’s disease [CD] and 10 with IBD unclassified [IBD-U]) were entered in UR-CARE. Among all registered patients, colorectal dysplasia was entered for 19 (6.93%) persons (15 males; 14 with UC). The column for “Dysplasia” in the drop-down menu could be left empty. These 19 patients with colorectal dysplasia make up 7.98% of all 238 patients with filled in one of the three options for dysplasia. 7 (2.55%) IBD patients (5 males; 5 with UC) had primary sclerosing cholangitis, and for two of them with UC, colorectal dysplasia was entered. Among all registered IBD patients, four had undergone surgery for CRC, and one patient was operated on for familial adenomatous polyposis. UR-CARE filtered 73 patients with extensive and left-sided UC with a duration of UC ≥ 8 years who should undergo screening colonoscopy for dysplasia. Conclusion UR-CARE can quickly and effectively differentiate patients with IBD and at an increased risk of developing CRC. It enables the provision of graphic data and provides access to the files of patients at high risk of CRC, allowing for their individual follow-up.

P679 Anti-TNF de-escalation following a treat-to-target strategy with golimumab therapy intensification to reach continuous clinical response in ulcerative colitis: the In-Target GETAID trial

Abstract Background Achieving deep and continuous remission with tight control could allow de-escalation in patients with UC. The in-TARGET study was a prospective two-phase trial in UC patients initiating golimumab (GLM), that aimed to determine the proportion of patients with continuous clinical response (CCR) and endoscopic remission (ER) after one year of treatment optimization strategy (phase 1); then to assess treatment de-escalation outcome in these patients (phase 2). Methods This was a multicentre prospective interventional study in GETAID centres. The study included adult patients with active UC (Mayo Score ≥6 with an endoscopic subscore ≥2), naive to biologics. In the first part of the study, patients received a conventional GLM regimen, depending on their weight (<80 kg; ≥80 kg). At week 10, primary responders continued with the standard maintenance regimen (50 mg or 100 mg/4 w) and non-primary responders had systematic treatment optimization (<80 kg, GLM 100mg/4 w; ≥80kg, introduction of an immunosuppressant) (Figure 1). In the second part of the study, patients in CCR and in ER (Mayo endoscopic score 0-1) at w 54, had treatment de-escalation: GLM discontinuation for patients receiving 50mg, and dose de-escalation to 50mg for those receiving 100mg. Results A total of 197 patients were included, mean duration of UC was 75.9 (± 95.3) months, the mean total Mayo score was 8.4 (± 1.7). At w 10, 14 patients had stopped treatment for failure, 83 (42.1%) had a primary response, and 100 (50.7%) non-primary responders had treatment optimization. At w 54, 95 (48.2%) patients were still on GLM; of these, 64 (32.5%) patients were in CCR and ER. At w 0 and 10, no factors were associated with CCR + ER at w54. Serum GLM levels after w10 were not associated with CCR and ER at w54. No patient developed anti-GLM antibodies between w0 and w54. Sixty patients participated in the second de-escalation phase of the study: in 18 GLM was discontinued, in 38 GLM dose was de-escalated from 100 to 50mg/4 w, and 4 patients refused dose de-escalation. At w 108, 34/56 (60.7%) patients were in CCR and ER, with no change in treatment. No factors were associated with w108 remission. At w108, 23 patients had relapsed: 4/18 (22.2%) among GLM discontinuations, 19/38 (50%) among patients de-escalated from 100 to 50 mg/4w. During follow-up, no colectomy was reported, and 14 severe non-UC related adverse events occurred (3 severe infections, 2 severe anaemias, and 1 rectal cancer). Conclusion One third of UC patients achieved a CCR with ER at one year with optimized GLM therapy. After de-escalation of GLM, 60% of remitters at one year maintained deep remission at two years. Anti-TNF de-escalation following a treat-to-target strategy could be considered in some UC patients.

A181 HIGHER CUMULATIVE HISTOLOGIC INFLAMMATORY BURDEN SCORE IS ASSOCIATED WITH THE RISK OF DEVELOPMENT OF COLORECTAL NEOPLASIA IN ULCERATIVE COLITIS

Abstract Background Ulcerative colitis (UC) patients have an elevated risk of colorectal neoplasia (CRN). Younger age at diagnosis, extent of colitis, and longer duration of colitis, as well as increased severity, which is a component of the cumulative inflammatory burden score (CIB), have been associated with the development of CRN. CIB was developed based on a large cohort of UC patients from St. Mark’s Hospital (UK) but needs further validation in independent cohorts. Purpose We analyzed the association between higher histologic CIB and development of CRN in longstanding UC patients. Method A matched case-control cohort of UC patients with at least 8 years of disease duration was analyzed at Mount Sinai Hospital. Patients with primary sclerosing cholangitis were excluded. Cases consisted of UC patients with colitis-associated neoplasia defined as indefinite for dysplasia (IND), low-grade dysplasia (LGD), high-grade dysplasia (HGD), or colorectal cancer (CRC). Each case was matched to two controls by age at disease onset, disease duration, and histological extent of colitis. Histologic reports obtained by colonoscopy were reviewed and histological activity was assessed as quiescent/normal (0), mild (1), moderate (2), and severe (3). The colonic area with the higher score was utilized and the CIB was calculated by summing each score and multiplying it by the interval of surveillance. A mean CIB (mCIB) was also calculated for each patient dividing the CIB by the number of colonoscopies. Continuous variables including CIB scores and mCIB scores were summarized as median and interquartile range (IQR) and differences between groups were compared by Mann-Whitney test. Result(s) Fifty-four UC patients were analyzed with 18 having CRN (6 CRC, 2 HGD, 3 LGD and 7 IND) and 36 controls without CRN. The clinical characteristics of the total cohort, cases and controls are depicted in the Table. Median age at last colonoscopy assessed was 45 years (36-55) and 40.7% were female. The median age at onset of UC was 23 years (19-37) and median duration of UC was 16 years (11-23). All patients had extensive histologic colonic disease. There were no differences between cases and controls in interval of surveillance evaluated (7.5 vs 7.8 years, p = 0.7) and median number of colonoscopies with histologic assessment (4 vs 4, p =0.6). Cases with CRN had significantly higher CIB (11.4 vs 7.9, p = 0.02) and mCIB (2.9 vs 2.0, p = 0.02) compared to controls. Image Conclusion(s) The histologic CIB score is associated with an increased risk of developing CRN in UC patients with similar age at onset of disease, disease duration and colitis extent. Given CIB reflects the severity of histologic inflammation over the years, treatment strategies to improve histologic inflammation could reduce the incidence of CRN in UC. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared

USE OF UPADACITINIB IN 11 TOFACITINIB-REFRACTORY ULCERATIVE COLITIS PATIENTS AT A SINGLE TERTIARY CARE CENTER

Abstract INTRODUCTION Ulcerative colitis (UC) is a chronic inflammatory condition characterized by diarrhea, abdominal pain, rectal bleeding, and weight loss. Upadacitinib is an oral, selective, small molecule Janus Kinase (JAK) inhibitor that was recently approved in the United States for moderate to severe UC. Clinical trials evaluating the efficacy of upadacitinib excluded patients with a previous exposure to tofacitinib, a nonselective JAK inhibitor; therefore, the efficacy of upadacitinib in patients with previous exposure to tofacitinib remains largely unknown. METHODS We present a small retrospective case series of all patients with a diagnosis of ulcerative colitis seen at our institution between with a prior exposure to tofacitinib who were initiated on upadacitinib between May and August of 2022. Demographic data was collected as well as outcome data on clinical improvement, steroid-free remission, biochemical improvement, colectomy status, and adverse events. RESULTS Eleven tofacitinib-refractory patients with ulcerative colitis were initiated on upadacitinib. Mean age was 38.1 years, five (45.5%) patients were female, nine (81.8%) patients were white, seven (63.6%) patients had pancolitis, and mean duration of UC was 7.4 years (Table 1). In this group, there were high rates of prior targeted therapy failures. These patients were followed for a mean of 121 days. The clinical course of each patient is presented in Table 2. Of the 11 patients included in our study, nine (81.8%) patients reported symptomatic improvement, six (54.5%) patients were able to successfully taper corticosteroids, and two (18.2%) patients underwent colectomy, one of which was elective and planned prior to initiating upadacitinib. The mean fecal calprotectin improvement was 1430mg/kg of patients with both baseline and follow-up testing. Three (27.3%) patients experienced an adverse event; two (18.2%) patients with mild COVID-19 not requiring hospitalization and one (9.1%) patient with Enteropathogenic E. Coli. DISCUSSION This real-world single-center case series of 11 patients, suggests that upadacitinib may be an effective option for patients with a previous tofacitinib exposure. Larger prospective studies are needed to confirm these findings.

Cost-Benefit Analysis: The UC Duration on the Unemployment Rate

Cost-Benefit Analysis: The UC Duration on the Unemployment Rate

DOP76 Real-world multicenter comparison of effectiveness between tofacitinib and vedolizumab in patients with Ulcerative Colitis after failure to at least one anti-TNF agent

Abstract Background Several therapeutic options are now available in ulcerative colitis after anti-TNF failure, but no data compared hitherto tofacitinib and vedolizumab. We compared the effectiveness of tofacitinib and vedolizumab in UC patients with prior exposure ≥ 1 anti-TNF. Methods In this multicentre retrospective study, we consecutively included all adult UC patients with partial Mayo score > 2, with ≥ 1 prior anti-TNF agent and started either tofacitinib (10mg b.i.d ± decreased to 5 mg b.i.d from week 8 (W8)) or vedolizumab (300 mg IV at W0-W2-W6 -W14 [± additional W10]) between January 2019 and June 2021. The primary endpoint was corticosteroid-free clinical remission or CFREM (partial Mayo score ≤ 2) at W16. Secondary endpoints were endoscopic improvement (CFREM + endoscopic Mayo score ≤ 1) and mucosal healing (CFREM + endoscopic and histological remission defined as Nancy index ≤ 1). All the comparisons were performed using propensity score analyses (inverse probability of treatment weighting) adjusted on gender, smoking, UC duration and extent, number of prior biologics or prior primary failure to biologics, concomitant 5-ASA, steroids or immunosuppressive agents, and disease severity. Results Overall, 400 patients will be included. Among the 200 first patients, 87 and 112 received tofacitinib and vedolizumab, respectively (one missing patient). Except for more pancolitis (54.0% vs 38.4%, p=0.028), less immunosuppressive therapies (4.6% vs 27.7%, p < 0.001), and higher rate of prior exposure ≥ 2 biologics (87.4% vs 37.5%, p < 0.001) in tofacitinib arm, baseline characteristics were similar across the two groups including concomitant 5-ASA (10.3% vs 18.8%) and steroids (23.0% vs 31.2%). Vedolizumab infusion at W10 was performed in 34.3% while 42.5% received tofacitinib 10 mg b.i.d until W16. CFREM was achieved in 54.2% and 42.5% in tofacitinib and vedolizumab, respectively p=0.089). The rate of CFREM at W16 was 57.4% vs 51.1% (p=0.77) after one biologic, 55.4% vs 41.8% (p=0.61) after 2 biologics, 56.9% vs 6.3% (p=0.007) after at least 3 biologics, and 59.0% vs 33.3% (p=0.17) in the subgroup with partial Mayo score ≥ 6, in tofacitinib and vedolizumab groups, respectively. Tofacitinib was more effective than vedolizumab to achieve CFREM at W16 in patients with primary failure to at least biologic (71.6% vs 30.8%, p=0.049). Among 177 patients, endoscopic improvement was higher in patients treated with tofacitinib (33.6 % vs 7.1%, p=0.048). Mucosal healing was observed in 6.4% vs 3.8% in tofacitinib and vedolizumab arms, respectively (p=0.27). Conclusion Tofacitinib and vedolizumab are effective after failure to anti-TNF agents. Tofacitinib seems to be more effective in case of primary failure to biologics and multiple therapeutic failure.

Regional Gray Matter Volume Changes in Brains of Patients With Ulcerative Colitis.

Ulcerative colitis (UC) and Crohn's disease (CD) are 2 subtypes of inflammatory bowel disease (IBD). Several studies have reported brain abnormalities in IBD patients. This study aims to identify differences of gray matter volume (GMV) between patients with UC and healthy controls (HCs). Fifty-seven patients with UC and 40 HCs underwent structural magnetic resonance imaging. Voxel-based morphometry method was used to detect GMV differences. Receiver operating characteristic (ROC) curve was applied to investigate reliable biomarkers for identifying patients with UC from HCs. Regression analysis was used to examine relationships between the structure alternations and clinical symptoms. Compared with HCs, patients with UC showed decreased GMV in the insula, thalamus, pregenual anterior cingulate cortex, hippocampus/parahippocampus, amygdala, and temporal pole; they showed increased GMV in the putamen, supplementary motor area, periaqueductal gray, hypothalamus, and precentral gyrus. Receiver operating characteristic analysis showed the highest classification power of thalamus. The inclusion of anxiety and depression as covariates eliminated the differences in the right insula, pregenual anterior cingulate cortex, supplementary motor area, and precentral gyrus. Most of the GMV changes were found in active patients with UC, with few changes in patients with UC in remission. We also found significantly negative correlation between UC duration and GMV in several regions. The current neuroimaging findings were involved in visceral sensory pathways and were partially associated with the levels of anxiety and depression and clinical stage of patients with UC. This study might provide evidence for possible neuromechanisms of UC.

P237 Prevalence of dysplasia and colorectal cancer in Ulcerative Colitis patients from a referral center in Latin America

Abstract Background Ulcerative colitis (UC) is a chronic inflammatory disease characterized by relapsing and remitting course of bloody diarrhea. UC patients are at higher risk of dysplasia and colorectal cancer (CRC) when compared to the general population, especially those with primary sclerosing cholangitis (PSC), long-standing disease and active inflammation. The aim of this study was to determine the prevalence of dysplasia and CRC in a large cohort of UC patients in Latin America. Methods This study was a retrospective analysis of all UC patients registered and followed-up in our outpatient clinic between January 2010 and September 2020. The diagnosis was confirmed by clinical, endoscopic, histopathological, and radiologic findings according to current guidelines. CRC was confirmed by one or more experienced pathologists. Medical records were abstracted for the data: demographic characteristics; duration, extent, and treatment of UC; dysplasia and cancer. Results In total, 560 patients with UC were identified. Of all cases, 364 (64.8%) had pancolitis, 115 (20.5%) had left side colitis and 81 (14.4%) were diagnosed with proctitis. There was a slight predominance of female, 331 (59.1%). The mean age at inclusion was 48 years. Among these patients 11.2% had concomitant PSC. Aminosalicylates were the most common treatment in 70% of our cohort, whereas 40% were treated with immunobiologics at any time during UC course. The length of the disease was between 10 to 20 years in 42% of cases and from 20 to 30 years in 17% of them. In our analysis the prevalence of dysplasia was 21%. Five of them were of high grade, which occurred in whom the length of the disease was between 10 to 20 years. In the majority of cases dysplasia was related to the inflammatory burden of UC (75.2%) and 37 patients were diagnosed with sporadic dysplasia. Seven cases (1.25%) of colorectal cancer were found (median time from UC diagnosis to CRC = 18 years), which two of these patients had concomitant PSC. All UC-CRC patients had extensive colitis. Conclusion Recent studies have suggested that the risk of CRC in UC population has decreased during the last decades due to tight control treatment and adequate endoscopic surveillance. In Latin America data on the prevalence and prognosis of UC-CRC patients are scarce. Herein we report the frequency of UC-related dysplasia and UC-CRC in Brazil over a period of 10 years. Our results revealed higher prevalence rates when compared to underdeveloped countries, such as India and China. Longer disease duration and extensive colitis were identified as important risk factors for developing CRC in accordance with the literature. Further research is warranted to better identify ethnical and environmental risk factors in this population.

Intensified Infliximab Induction is Associated with Improved Response and Decreased Colectomy in Steroid-Refractory Paediatric Ulcerative Colitis.

Infliximab pharmacokinetics in steroid-refractory [SR] ulcerative colitis [UC] suggest a need for higher dosing, but data concerning efficacy of intensification in this setting are lacking in children and inconsistent overall. Paediatric patients [N = 125] treated with infliximab for SR or steroid-dependent UC were retrospectively reviewed. Outcomes [clinical response and remission, colectomy, mucosal healing, safety] with standard vs intensified induction [mean induction dose ≥7 mg/kg or interval ≤5 weeks between doses 1 and 3] were compared. Among 125 patients [median age 14 years, median UC duration 0.7 years, 74 SR], 73 [58%] received standard induction and 52 [42%] received intensified induction. Overall, 73 [58%] achieved remission (judged by physician global assessment [PGA] and paediatric UC activity index [PUCAI]≤10]. Among patients in remission, 7 [10%] experienced secondary loss of response by a median of 0.7 [IQR 0.4-1.0] years. Of the 74 SR patients, 17 [23%] underwent colectomy, and of the 51 steroid-dependent patients, 12 [24%] underwent colectomy. Intensified induction in SR patients was associated with a higher chance of remission (hazard ratio [HR] 3.2, p = 0.02) and a lower chance of colectomy [HR 0.4, p = 0.05], but did not improve outcomes in steroid-dependent patients. During follow-up, 46/73 [63%] patients in remission had regimen individualization, with similar rates of return to standard dosing after 1 year between those with initial intensified or standard induction. Follow-up endoscopy, performed in 35/73 patients in remission, demonstrated mucosal healing for 66%. Adverse events were rare, despite use of intensified regimens. These data suggest a benefit from intensified infliximab induction specifically among children with steroid-refractory UC. Prospective studies comparing dosing regimens and incorporating therapeutic drug monitoring should be undertaken.

Colonic Mucosal Transcriptomic Changes in Patients with Long-Duration Ulcerative Colitis Revealed Colitis-Associated Cancer Pathways.

Background and aimsPatients with ulcerative colitis [UC] with long disease duration have a higher risk of developing colitis-associated cancer [CAC] compared with patients with short-duration UC. The aim of this study was to identify transcriptomic differences associated with the duration of UC disease.MethodsWe conducted transcriptome profiling on 32 colonic biopsies [11 long-duration UC, ≥20 years; and 21 short-duration UC, ≤5 years] using Affymetrix Human Transcriptome Array 2.0. Differentially expressed genes [fold change > 1.5, p < 0.05] and alternative splicing events [splicing index > 1.5, p < 0.05] were determined using the Transcriptome Analysis Console. KOBAS 3.0 and DAVID 6.8 were used for KEGG and GO analysis. Selected genes from microarray analysis were validated using qPCR.ResultsThere were 640 differentially expressed genes between both groups. The top ten upregulated genes were HMGCS2, UGT2A3 isoforms, B4GALNT2, MEP1B, GUCA2B, ADH1C, OTOP2, SLC9A3, and LYPD8; the top ten downregulated genes were PI3, DUOX2, VNN1, SLC6A14, GREM1, MMP1, CXCL1, TNIP3, TFF1, and LCN2. Among the 123 altered KEGG pathways, the most significant were metabolic pathways; fatty acid degradation; valine, leucine, and isoleucine degradation; the peroxisome proliferator–activated receptor signalling pathway; and bile secretion, which were previously linked with CAC. Analysis showed that 3560 genes exhibited differential alternative splicing between long- and short-duration UC. Among them, 374 were differentially expressed, underscoring the intrinsic relationship between altered gene expression and alternative splicing.ConclusionsLong-duration UC patients have altered gene expressions, pathways, and alternative splicing events as compared with short-duration UC patients, and these could be further validated to improve our understanding of the pathogenesis of CAC.

P750 Predictors of quick remission after cyclosporine A therapy in Paediatric ulcerative colitis

Cyclosporin A is a second-line drug in ulcerative colitis that failed to respond to intravenous glucocorticoids according to ECCO/ESPGHAN consensus . Up-to-date CsA induced mucosal healing (Mayo 0 score) is the only factor predicting the lack of course deterioration in the future. The aim of the study was to investigate a presence of factors contributing to positive CsA therapy outcome. It is a retrospective, single center study. We describe a clinical characteristic of 59 children (33 females, 26 males), mean age of 13.7 years, mean disease duration 32 months, who underwent CsA treatment in the course of UC in years 2005–2015. The primary endpoint was clinical remission (defined as PUCAI<10) or clinical response (defined as decrease in PUCAI scoring for at least 20 points) at Day 8. Response/remission at Day 8 was achieved in 43 out of 59 (81%) and 31 out of 59 (58%) patients, respectively. Clinical (PUCAI score), laboratory (CsA concentration), endoscopic (disease extension and severity) and demographic (age, age of onset, disease duration) data were used as independent variables in analysis of discrimination between: group with clinical response vs. no response and group with clinical remission vs. no remission. PUCAI score, UC duration and Mayo score create the model which predict clinical remission at Day 8 with sensitivity 0.8 and specificity 0.66. No model was established to discriminate between groups with clinical response vs. no response. PUCAI score, UC duration and Mayo score contribute to response for induction therapy with CsA in children with UC.

MESALAZINE PLACE IN THERAPY OF ULCERATIVE COLITIS

Preparations of 5-aminosalycil acid (Mesalazine) are used as the first-line therapy to induce remission if the UC activity is minimal and as the priority drugs for anti-recurrence therapy of patients with UC and are included in the Russian recommendations on the therapy of the colitis of the slight and moderate activity. The choice of the drug and its form requires individual approach, it must be based on the UC duration, activity of the inflammatory process as of the moment of the treatment decision taking, the drug safety profile, its effectiveness and tolerability.

Effect of Adalimumab Dose Escalation on Hospitalization Risk in Patients With Moderately to Severely Active Ulcerative Colitis

Introduction: We assessed the effect of adalimumab dose escalation on risk of hospitalization in patients with moderately to severely active UC who did not respond or lost response after adalimumab induction therapy. Methods: Data were pooled from two randomized, double-blind, placebo-controlled phase 3 trials of adalimumab in patients with moderately to severely active UC (ULTRA 1 and 2: NCT00385736; NCT00408629). Patients randomized to adalimumab 160/80 mg induction therapy at weeks 0/2 followed by adalimumab 40 mg EOW who later dose escalated to 40 mg every week owing to non-response or loss of response were included in the analysis. Kaplan-Meier time-to-event analysis was used to estimate observed risks of all-cause and UC-related hospitalization within 90 days after dose escalation. Cox proportional hazards models were used to establish the relationship between hospitalization (both all-cause and UC-related) and partial Mayo scores after dose escalation, controlling for age, sex, prior anti-tumor necrosis factor (anti-TNF) status (naive or experienced), and partial Mayo score before dose escalation. This model's coefficients were then used to predict the 90-day all-cause and UC-related hospitalization risks had no dose escalation occurred, by assuming no changes in patients' partial Mayo scores in the period after dose escalation vs before dose escalation. Results: Of 122 patients who escalated to weekly adalimumab dosing, the majority were male (68%) and naive to anti-TNF agents (74%); mean age was 39.5 years and mean UC duration was 8.3 years. Mean partial Mayo score decreased from 6.8 before dose escalation to an average of 5.17 after dose escalation. For patients who dose escalated, the observed (Kaplan Meier) 90-day all-cause and UC-related hospitalization risks were 8.7% and 6.7%, respectively. The predicted 90-day all-cause and UC-related hospitalization risks, had patients continued on EOW therapy, were 13.0% and 10.3%, respectively. The relative risk of both all-cause and UC-related hospitalization in patients who dose escalated was lowered by 33.2% and 35.5%, respectively, compared with the predicted risk without dose escalation, reflecting the benefits of dose adjustment. Conclusion: Dose escalation of adalimumab in patients with moderately to severely active UC who did not respond or lost response after induction therapy reduced the 90-day risk of hospitalization and reflected a benefit of adalimumab dose escalation for treating these UC patients.

A clinical significance of assessing cytomegalovirus infection status in patients with ulcerative colitis.

A clinical significance of assessing cytomegalovirus infection status in patients with ulcerative colitis.

Su1344 Failure of Infliximab Treatment in Crohn's Disease Is Associated With the Presence of Fibrosis

G A A b st ra ct s operated for colon cancer without UC served as controls. On HE 29% vs 33% vs 54%, p=0.009). Between acute and late UC there was no difference in collagen deposition, however between UC together and controls there was more collagen I expression in the mucosa, MM and muscularis externa (50% vs 10%, p=0.02; 28% vs 10%, p=0.048; 71% vs 20%, p=0.003). In both early and long UC duration, we did not find a correlation between inflammation or collagen deposition or MM thickness. There was a negative correlation between inflammation andαSMApositivity in the submucosa (R=-0.51, p=0.003) and MM (R=-0.37, p=0.04). Conclusion In our series of colectomy specimens, there is more collagen deposition in UC than in controls. No association between disease duration and increased collagen deposition could be found. Expression of αSMA however is lower in UC and correlates with inflammation. Fibrosis in UC does not appear to increase significantly over time.

DOP067 Low FODMAP diet reduces irritable bowel symptoms and improves quality of life in patients with inflammatory bowel disease in a randomized controlled trial

University/Hospital. Data were expressed as median and range and differences between groups assessed by the T test. Results: Dermatological assessment was performed in 188 IBD patients (85 F, age 45.5 yrs, range 18 85; IBD duration 9 yrs, range 1 46). Among these 188 patients, there were 72 UC (35 M, age 47, range 23 85; UC duration 6 yrs, range 1 40; UC extent: distal 26, left 11, extensive 31, ileal pouch 3, ileostomy 1) and 116 CD (69 M, age 44, range 18 80; CD duration 10 yrs, range 1 46; CD colitis 8, ileo-colitis 24, ileitis 34, neo-terminal ileum 45, ileostomy 2, jejunum 1, distal ileum + jejunum 2). NonIBD C included 50 patients (31 M, age 47, range 18 75). Among the 188 IBD patients, psoriasis was detected in 48 (26%; 28 CD, 20 UC). In the IBD group, the median age and IBD duration were comparable in patients with or without psoriasis (age 50.5 range 23 72 vs 44 range 18 85; IBD duration 8 yrs range 1 45 vs 9 yrs range 1 41; p = ns for both). Mild psoriasis was detected in a higher proportion of IBD patients (40/48; 83%) than nonIBD C (28/50; 56%; p < 0.001). Scalp psoriasis and sebopsoriasis were the more common psoriasis phenotype in IBD (16/48; 33%), followed by inverse psoriasis (7/48; 15%) and by palmoplantar psoriasis (5/48; 10%). Psoriatic arthritis was detected in 9/50 (18%) non-IBD C and in 4/48 (8%) IBD patients (p = n.s.). In 4/48 (12%) IBD patients, psoriasis developed after anti-TNFs (palmo-palmar 3, sebopsoriasis 1). Conclusions: Results from a cohort of IBD patients matched with non-IBD control patients suggest that specific phenotypes of psoriasis may be associated with IBD.

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Introduction: Catheter associated urinary tract infections (CAUTI) are the second most common cause of healthcare associated infections (HAI), with a daily risk ranging from 3 to 7%. In May 2012, surveillance in our Pediatric Intensive Care Unit (PICU) identified CAUTI rates and urinary catheter utilization (UCU) above 75th percentile for those in National Healthcare Safety Network (NHSN). The purpose of this quality improvement (QI) project was to reduce CAUTI and UCU. Methods: In July 2012, a multidisciplinary QI team introduced two evidence-based interventions in a staged fashion: 1) daily UC needs assessment and 2) hourly documentation of an indication of UC by a bedside nurse in electronic medical record by selecting an option from a drop down menu. Standard NHSN reporting definitions were used to define CAUTI, UCU ratio (UC days/patient days) and CAUTI rates per 1000 UC days. Rates of CAUTI pre (July 2011 to June 2012) and post (July 2012 to June 2013) intervention were compared using the generalized estimating equation Poisson regression analysis. Duration of UC per patient (n=26) and compliance with documentation of indication for UC (88 UC days) were audited post intervention for a 2-month period. Results: Six CAUTIs occurred during the study period (5/842 UC days pre and 1/439 UC days post intervention). Implementation of the interventions reduced CAUTI rates from a mean of 5.94 (CI:2.8-12.6) to 2.28 (CI:0.4-14)(p=0.26). UCU ratio reduced significantly (p<0.0001) from 0.31 (CI:0.25-0.37) to 0.15 (CI:0.13-0.16). Eighty five percent patients had UC for ≤4 days. Compliance with documentation of indication for UC was 100%. 'Measurement of accurate urine output' was selected as an indication for 95% of UC days, suggesting need for more education on documentation. Conclusions: HAIs are a continual challenge to quality care. Evidence is growing that HAI's are avoidable through the use of best practices. Implementation of bundled interventions significantly reduced UCU. CAUTI rates reduced below reported 2011 NHSN mean (3.1) but did not meet statistical significance likely due to the small number of CAUTIs per 1000 UC days. Longer time frame is likely needed to prove statistical reduction in CAUTI rates.

Clinical value of serum eosinophilic cationic protein assessment in children with inflammatory bowel disease.

IntroductionEosinophils contribute to the pathogenesis of inflammatory bowel disease (IBD) in the intestine. Eosinophilic cationic protein (ECP) is one of the most important eosinophilic specific mediators released during activation. The aim of the study was to evaluate the clinical value of serum ECP determination in children with active and inactive IBD and its correlation with disease activity.Material and methodsThere were 125 children with IBD (63 with Crohn's disease – CD, 44 with ulcerative colitis – UC, 18 indeterminate colitis – IC) enrolled in the study. Among them 83 children were in the active phase of the disease, while the remaining 42 were in remission. The control group consisted of 56 healthy children. The ECP was assessed three times in children with active IBD, at baseline and after 2 and 6 weeks of treatment and once in children with inactive IBD and controls using fluoroenzymeimmunoassays.ResultsWe found elevated ECP at baseline in the total active IBD group when compared to the inactive IBD and control groups, decreasing during treatment. Serum ECP was also elevated in the active UC and CD groups when compared to the inactive UC and CD groups, and correlated with clinical UC and CD activity (R = 0.57 and R = 0.52, p < 0.05, respectively) and duration of the clinical manifestation in UC (R = 0.62, p < 0.05) but not with the disease location in the gastrointestinal tract, or endoscopic and histopathological activity.ConclusionsEvaluation of serum ECP in children with IBD may be useful in disease activity assessment at onset and during the treatment.

P346 The experience of restorative proctocolectomy for ulcerative colitis during 1985–2009

Methods: We retrospectively reviewed 106 patients with steroid-dependent UC for whom azathioprine was started between October 1998 and May 2009. Six-month and 3-year outcomes after azathioprine therapy were evaluated. Results: Of the 106 patients, 73 (68.9%) were continued on azathioprine for more than six months (azathioprine group) and 33 (31.1%) discontinued azathioprine within six months due to intolerance (intolerance group, n = 20), colectomy (n = 6) or follow-up loss (n = 7). The most common reasons for intolerance were nausea and vomiting (n = 5), elevated liver enzymes (n = 5) and hair loss (n = 5). Six-month and 3-year outcomes for all 106 patients were remission in 70 (66%) and 67 (63.2%), corticosteroid dependence in 17 (16%) and 5 (4.7%), infliximab administration in 3 (2.8%) and 6 (5.6%), colectomy in 8 (7.5%) and 15 (14.2%), follow-up loss in 8 (7.5%) and 12 (11.3%), and death in 0 (0%) and 1 (0.9%), respectively. Six-month and 3-year outcomes for azathioprine group were remission in 57 (78%) and 60 (82.2%), corticosteroid dependence in 16 (22%) and 3 (4.1%), infliximab administration in 0 (0%) and 3 (4.1%), colectomy in 0 (0%) and 2 (2.7%), follow-up loss in 0 (0%) and 4 (5.4%), and death in 0 (0%) and 1 (1.3%), respectively. The azathioprine (n = 73) and the intolerance (n = 20) groups showed no significant difference in median age at diagnosis (37 years vs. 45 years, P= 0.17), proportion of male patients (61.6% vs. 40%, P= 0.12), median age at azathioprine therapy (40 years vs. 46 years, P= 0.27), median duration of UC before azathioprine (35.2 months vs. 17.6 months, P= 0.06), and median dose of azathioprine (1.06mg/kg vs. 0.83mg/kg, P= 0.39). The proportion of the patients remaining in remission was higher (88.2% vs. 36.8%, P< 0.001) in the azathioprine group compared with the intolerance group. Conclusions: Azathioprine is an effective treatment for steroiddependent UC. The efficacy of azathioprine is well sustained for 3 years. This study was supported by a grant of the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (A120176).

Correlation between serum serotonin and endoscopy inflammation scores in patients with ileal pouches

BackgroundInflammatory and functional complications are common in patients with inflammatory bowel disease (IBD) after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA). The pathogenesis of these complications remains poorly understood, and there is discrepancy between the clinical symptoms and objective endoscopic inflammation scores in these patients. While serum serotonin level has been reported to be associated with symptoms of irritable bowel syndrome, its association with ileal pouch disorders has not been studied. AimTo investigate the association between serum serotonin level and symptoms and endoscopic inflammation in patients with IPAA. MethodsA total of 185 consecutive eligible IPAA patients who presented to a specialized Pouchitis Clinic from Jan 2009 to May 2009 were prospectively recruited. Patients were divided into 4 groups: normal pouch, irritable pouch syndrome (IPS), inflammatory pouch disorders (Crohn's disease, acute and chronic pouchitis, and cuffitis), and surgical complications. Serum serotonin level was measured and analyzed for correlation with clinical and endoscopic inflammation scores. ResultsDemographic and clinical variables were evaluated, including age, gender, smoking history, duration of UC, duration of the pouch, and disease category of the pouch. The median fasting serum serotonin level was comparable among the 4 groups: 94.0ng/ml (interquartile range [IQR], 70.0, 128.1), 89.2ng/ml (IQR 54.2, 155.9), 90.3ng/ml (IQR 49.7, 164.1), 77.9ng/ml (IQR 54.7, 129.0), for normal pouch, irritable pouch, inflammatory pouch disorders, and surgical complication groups, respectively (p=0.91). A significant association between serum serotonin level and the Pouchitis Disease Activity Index (PDAI) endoscopy subscore of the pouch (odds ratio [OR]=1.9, 95% confidence interval [CI]: 1.2, 2.9, p<0.05) and total PDAI endoscopy score (OR=1.8; 95% CI: 1.2, 2.8, p<0.05) in the inflammatory complication group were noted. ConclusionsSerum serotonin level appears to correlate with the PDAI endoscopy subscores and total PDAI score in patients with inflammatory complications suggesting that the hormone may be involved in mechanisms of mucosal inflammation. These findings may promote future treatment strategies for patients with pouch inflammation.