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A Retrospective Multicenter Survey on Infliximab Efficacy and Safety inModerate-to-Severe and Steroid-Dependent Ulcerative ColitisMaria Cappello, Marta Mazza, Giuseppe Costantino, Walter Fries, Antonino C. Privitera,Mauro Mastronardi, Nello Buccianti, Fabiana Castiglione, Antonio Rispo, Angelo Lauria,Raffaella Marasco, Piero L. Almasio, Fabrizio Bossa

Background and aim: Infliximab (IFX) has been shown effective both for induction andmaintenance of remission in moderate-to-severely active ulcerative colitis (UC). The aim ofthis retrospective multicenter study is to provide data on short and long-term efficacy andsafety of IFX in UC in a "real life" setting. Methods: data were extracted from clinical recordsof consecutive patients with biopsy proven UC who received at least one infusion of IFXfrom January 2008 to June 2012 in nine referral centers from Southern Italy. Clinicaland demographic characteristics, IFX indications, concomitant medications, disease activity(Mayo score), date of colectomy, and adverse events were registered. Outcomes of efficacywere clinical and endoscopic responses at week 14 and 52, steroid-free remission, mucosalhealing and colectomy rate. Result: The study included 257 adult patients with UC (58.4%males, mean age 35.7, range 10-78) treated with scheduled IFX 5 mg/kg. Median durationof UC was 50 months (IQR 18-115), and the extension of disease was pancolitis in 185(72.0%) subjects, left-sided colitis in 57 (22.2%), and proctosigmoiditis in 15 (5.8%).Indication to IFX were steroid dependence in 74.7% of patients, steroid-resistance in 23.0%,extra-intestinal complications in 2.3%. Thiopurine failure or intolerance was reported in40.5%. IFX was used as rescue therapy in 5.8% of patients with severe refractory UC.Patients received a median of 9 infusions (range 1-40) and median follow-up was 26 months.IFX optimization for loss of response was necessary in 39 (15.2%). Overall median Mayoscore was 9 (IQR 7-10) at enrolment, 5 (IQR 2-6) at 14 weeks and 3 (IQR 1-5) at 52 weeks(p,0.001 by Anova). Remission rates were 32% at week 14, 39.4% at week 52. The rateof patients able to stop steroids were 42.0% at 14 weeks and 40.5% at 52 weeks. Mucosalhealing was obtained in 56.7%. Colectomy was performed in 22 patients (8.6%). Mediantime to colectomy was 7.1 months. Adverse events were observed in 51 (19.8%) of patients:20 infusion reactions, 22 opportunistic infections (7 patients with shingles). Four subjectsdeveloped "de novo" neoplasia (2 colo-rectal carcinoma). Conclusion: This is the first reportof a large open-label multicenter Italian series in "daily clinical practice". Infliximab is a safeand effective treatment in avoiding colectomy and inducing both short and long-term clinicalresponse and mucosal healing in moderate-to-severe UC.

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Anemia and Inflammatory Bowel Disease: Effects of High-Dose IntravenousIron Treatment on Hemoglobin, Activity Index and Quality of LifeJudith Millastre, S. García-López, Eduardo Bajador, Maria Chaparro, Fernando Gomollon,Javier P. Gisbert

Anemia is the most prevalent extraintestinal complication of Inflammatory Bowel Disease(IBD). Although the causes of anemia in IBD are multifactorial, Iron Deficiency Anemia(IDA) is the most common cause. Its correction can be highly effective to improving qualityof life of the patient. Treatment with high-dose intravenous iron (Fe-iv) (Carboximaltose)allows fast replacement in case of severe anemia (hemoglobin (Hb) ,10,5 gr/dl), even inpatients who have pronounced disease activity or oral intolerance. The objective of thisstudy is to evaluate efficacy and tolerability of Fe-iv, considering safety, hematological andquality of life (QoL) outcomes. Methods: Prospective analysis of a serie of IBD patientstreated with 1-2 infusions of Fe-iv Carboximaltose according to Ganzoni's formula. Inclusioncriteria were: Hb , 10,5 gr/dl, oral Fe intolerance or inefficiency. We analyze hematologicalparameters, QoL (CCVEII-9 score) and clinical activity of IBD (Truelove/Harvey-BradshawIndex) just before and 4 weeks after treatment. Treatment safety and possible adverse eventsare monitored. Results: We included 88 patients (55 (62,5%) women, 33 (37,5%) men, 57(64,8%) Crohn's Disease (CD), 31 (35,2%) Ulcerative Colitis (UC). The Montreal Classifica-tion was: EC:A1:11, A2:31, A3:15; B1:27, B2:16, B3:14; L1:19, L2:12, L3:26; CU: E1:5,E2:11, E3:12, Pouchitis:3. Activity disease: CD patients 71.1% inactive, 22,2% mild tomoderate, 6,7% severe. UC patients: 45% mild, 45% moderate, 10% severe. Hb increasedin 84 cases (95.4%), achieving normal Hb levels (complete response) in 28 patients (31.8%).See Table 1. Improvement in QoL(CCVEII-9 score) correlates with hematological response.We show the score average before and after treatment according to Hb increase. See Table2. No increase of activity disease was observed in any patient. Only 2 adverse events wereobserved,just one enough severe to stop therapy. Conclusions: IV Carboymaltose IronTreatment has proven effective and safe in our series, although with a modest recovery inhematological values. This finding may be due to the different degree of activity of thepatients enrolled in our study compared with other authors. After treatment there is auniversal improvement of QoL score, although statistically not significant.Table 1.- Hb INCREASE

Table 2.- QoL BASAL AND AFTER TREATMENT

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Mucosal Healing by Individual Anti TNF Agent in Crohn's Disease in TertiaryCare SettingZainab Ashir, Corinne Guilday, Yelena Zadvornova, Daniel Stein, Amar S. Naik, NandaVenu, Kari Best, Susan Skaros, Kia Saeian, Lilani P. Perera

Background: Recent studies have demonstrated that mucosal healing in patients with inflam-matory bowel disease (IBD; Crohn's disease [CD], ulcerative colitis [UC]) is associated withimproved outcomes in both CD and UC. The ability of different biologics to heal the mucosain CD has only been explored in various clinical trials as a secondary end point or in posthoc analyses. We retrospectively analyzed success of different biologics in achieving mucosalhealing at a single tertiary IBD referral center. Methods: Retrospective analysis of selectedcohort of CD patients treated with ATNF therapy (Infliximab: IFX, Adalimumab: ADA, andCertolizumab: CTZ) for a duration ≥6 months. All patients underwent pre- and post- therapycolonoscopy with biopsies (active and quiescent disease); those who had only small bowelinvolvement or no colonoscopy within 2 years of starting biologic therapy were excluded.Multiple logistic regression was used to compare outcomes. Results: Total 230 patients with96 (42%) on IFX, 93 (40%) on ADA and 41(18%) on CTZ therapy met criteria. Pre andpost treatment comparison test revealed microscopic and endoscopic mucosal (37%) healingin overall (p 0.003). 63% patients remained unchanged or worsened in microscopic andendoscopic disease severity. 17 % of unchanged patients had quiescent disease before andafter initiation of ATNF. There was statistically significant difference between individualATNF agents with infliximab showing superior mucosal healing (p 0.016). Mucosal healingwas significantly higher in patients who were younger at ATNF start (p 0.05), had shorterduration of disease (p 0.002), and had a non-penetrating phenotype (p 0.015). No statisticaldifference noted between healed and non healed patients in gender, ethnicity, diseasedistribution, smoking status, Harvey-Bradshaw index (HBI), ESR/CRP, Short InflammatoryBowel Disease Questionnaire (SIBDQ), hospitalizations or operations. Conclusions: DespiteANTF therapies resulting in both mucosal and histologic healing in 37% of CD patients,there was no discernible improvement in outcome compared to those who did not achievethese endpoints. The reasons for the absence of better outcomes including development ofmore sensitive measurement tools to assess benefit warrant further study. The finding thatinfliximab use achieved superior mucosal healing should be cautiously interpreted as 88%of IFX patient had no prior ATNF exposure compared to 59% for ADA and 42% for CTZ.

Table 1: Performance of individual ATNF agents

Table 2: Patient characteristics

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Persistent Vitamin D Insufficiency After High Dose Vitamin D Treatment inPatients With Inflammatory Bowel DiseaseYash A. Choksi, Julianne H. Wagnon, Caroline Duley, Anne Nohl, Dawn B. Beaulieu,David A. Schwartz, Sara N. Horst

Background: Vitamin D deficiency in patients (pts) with inflammatory bowel disease (IBD)is common, and more data regarding appropriate vitamin (vit) D replacement dosing isneeded. Our study aims to evaluate repeat serum vit D and bone health in pts with IBDwho received high-dose vit D treatment. Methods: A search of all pts seen at a tertiary caresingle medical center from Jan 1995 to Dec 2010 using a de-identified patient database was

conducted. Pts were included if they had an ICD-9 code with a diagnosis of IBD [Crohn'sdisease (CD) or ulcerative colitis (UC)], had a measured low vit D 25 OH level ( ,30 ng/mL), and were treated with high-dose vit D received high-dose vit D treatment (ergocalciferol50,000 units once a week for eight weeks). Outcomes included duel-energy x-ray absorpti-ometry (DEXA) scan measures and repeat vit D 25 -OH level if obtained before and afterhigh dose vit D treatment. Statistical analysis included Wilcoxon signed-rank test. Results:52 pts with IBD (39 CD, 13 UC), low vit D 25 OH levels, and treatment with high dosevit D were identified. 34 were male (66%), and the median age was 57 (range 22, 83 yrs).14 (27%) had one or more IBD-related surgeries. 11 were smokers (22%). 7 (13%) pts wereon corticosteroids, 8 (15%) pts were on budesonide, 20 (38%) were on immunomodulatortherapy, and 20 (38%) were on anti-TNF medications. 19 (37%) pts had a previous diagnosisof osteopenia, and 12 (23%) had osteoporosis. 19 (37%) were taking a bisphosphonate. 24(46%) had documented daily non-prescription vit D supplementation. 29 pts had a DEXAscan before and after high dose vit D treatment after a median of 2.1 yrs (range 1, 6.5 yrs).Spine bone mineral density (BMD) scores improved significantly (1.05 ± 0.17 to 1.10 ±0.20, p , 0.05). There was no significant change in BMD of the hip (0.79 ± .15 to 0.75 ±.31), and hip and spine T scores and Z scores did not change significantly. 36 pts hadrepeat vit D 25 OH levels checked after a median of 120 days (range 47, 964 days). Vit D25 OH increased significantly (15.5 ± 8.4 to 29.4 ± 19.0, p , 0.05). However, 14 (36%)pts remained vit D deficient (vit D 25 OH levels , 20 ng/mL), and 8 (22%) pts remainedvit D insufficient (vit D 25 OH levels 20-30 ng/mL). Persistent vit D insufficiency was notdependent on gender, surgical history, medication type, or disease type. Conclusion: In thisstudy, the majority patients with IBD who are vit D insufficient failed to achieve normalserum vit D levels after treatment with high dose vit D, but bone health based on DEXAscan did not worsen significantly. Further research into appropriate calcium and vit D dosingin this patient population is warranted.

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Short- and Long-Term Efficacy of Tacrolimus in Patients With RefractoryUlcerative ColitisOsamu Watanabe, Takafumi Ando, Kazuhiro Ishiguro, Osamu Maeda, Masaki Ujihara,Yutaka Hirayama, Kazuhiro Morise, Masanobu Matsushita, Keiko Maeda, Kohei Funasaka,Masanao Nakamura, Ryoji Miyahara, Naoki Ohmiya, Hidemi Goto

Background and aim: Many patients with steroid-refractory or steroid-dependent ulcerativecolitis (UC) are likely to require surgery in spite of pharmacological treatment. Tacrolimus,a calcineurin inhibitor, is expected to be an effective alternative drug which allows colectomyto be avoided. We retrospectively investigated patients with refractory UC treated withtacrolimus. Patients and methods: Forty patients with moderate or severe UC were treatedwith oral tacrolimus between July 2009 and June 2012 at our hospital. Dosage was adaptedto achieve trough levels between 10 and 20 ng/mL for the first two weeks and between 5and 10 ng/mL after the 3rd week. Azathioprine was administered in combination withtacrolimus to patients who had responded to it as long-term immunosuppressive therapy.Results: After four weeks of tacrolimus therapy, 23 patients (58%) showed a completeresponse to this therapy, 5 (13%) had mild to moderate disease activity, and 11 (28%)showed no response. One patient discontinued treatment due to light-headedness. Of the15 of 40 patients with severe disease, 9 (60%) obtained complete remission. Eleven of the15 patients with severe disease were fasted for the first two weeks, of whom 9 (82%) enteredcomplete remission, whereas 4 severe patients with oral intake were unresponsive to therapy.After 12 weeks of tacrolimus therapy, 25 of 28 patients who responded at the fourth weekremained in remission. Corticosteroids (CS) were then tapered and discontinued. The meandosage of CS was 18.5 mg/day before tacrolimus therapy and 2.1 mg/day after 12 weeks(p , 0.001). Twenty-one patients were treated with tacrolimus for more than six months,12 of whom received combination therapy with azathioprine (AZA). At a mean follow-upof 24 months, colectomy was avoided in 11 of these 12 patients with combined treatment,but in only 4 of 9 receiving monotherapy (p , 0.05). Conclusion: Oral tacrolimus waseffective in inducing remission in patients with steroid-refractory UC. Oral intake of foodmight be detrimental to the efficacy of tacrolimus in patients undergoing remission inductionwith this agent. With regard to maintenance therapy, tacrolimus alone was not effective inachieving lasting remission. Late colectomy was avoided by the addition of azathioprine tomaintenance therapy with tacrolimus.

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Structural and Functional Consequences of Surgical Intestinal Anastomoses inCrohn's DiseaseMahesh Gajendran, David G. Binion, Bettina M. Buchholz, Atsunori Nakao, William M.Rivers, Claudia M. Ramos Rivers, Katherine A. Weyant, Miguel Regueiro, Andrew R.Watson, Brian M. Davis, Anthony J. Bauer

Introduction: Most Crohn's disease (CD) pts require small bowel resection with end-to-end(E-E) or side-to-side (S-S) anastomosis. Stapled S-S has fewer short term complications, buttransection of circular muscle layers and reconstruction in an anti-peristaltic orientationdisrupts motility which can lead to stasis of enteric contents. There is limited data regardingthe effect of the anastomosis (E-E vs. S-S) on intestinal structure/function in CD pts andanimal models of IBD. Methods:CD pts with E-E and S-S anastomosis were evaluated 2years after first resection. A rat model of E-E and S-S intestinal anastomoses analyzed after21 days with/without oral DSS4% x 5 days. Intestinal histology, liquid and solid gastrointesti-nal transit (GIT) measurements were performed. Spontaneous and EFS-induced neuromuscu-lar contractile responses were assessed in anastomotic circular muscle strips. Results: Therewere 66 CD pts analyzed with 36 S-S (56% M; age 38.4 y; CD duration 7.8y) and 30 E-E(60%M; age 34.4 y; CD duration 6.5 y; p=NS). Post-op immunomodulator use was: S-S72% E-E 63.3% and biologic S-S 63.9% and E-E 46.7%. At 2 years post-op emergencydepartment visits were: S-S 28% (total 27 visits in 10 pts) vs. E-E 13% (11 visits in 4 pts).Abdominal CT scans 2 years post-op: S-S 42% (total of 27 scans in 15 pts) and 10% in E-E (4 scans in 3 pts) p=0.005. Post-op hospitalizations: S-S 25% (12 hospitalizations in 9pts) vs. E-E 10% (4 hospitalizations in 3 pts). Narcotic use was S-S 11% and E-E 3%. Meanquality of life in S-S was 47.5 and E-E was 51.3. Neo-TI inflammation at 2 yrs: S-S 43%

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and E-E 28%. Rat intestinal diameter was 3.7±0.8 mm in control, E-E 8.8±2.0 mm and S-S 23.6±2.4 mm with chyme accumulation. S-S+DSS significantly increase spleen weight(1958±453.9 vs. control 767±42.6 gr) presumable due to bacterial translocation. LiquidGIT showed no anastomotic obstruction. Solid GIT was similar in controls and E-E (wateror DSS). Solid GIT demonstrated significant 59.4% accumulation at the S-S induced reservoirand S-S+DSS had significant delay in gastric emptying (56.5%). Spontaneous contractilefrequency was similar between E-E and controls, but decreased in the S-S group,which wasaggravated by DSS (control=29.0±0.39, E-E=31.2±3.11 and S-S=9.7±1.06) (control+DSS=28.2±1.7, E-E+DSS=29.3±1.6 and S S+DSS=6.2±2.0). EFS-induced similar inhibition ofcontractions in control and E-E, but functional inhibitory response was diminished in the S-S group and EFS of S-S+DSS muscles produced a paradoxical excitatory contractile response.Conclusion:S-S anastomosis alters intestinal anatomy creating an anti-peristaltic reservoir,which results in dysmotility due to alterations in contractility and innervation. These struc-tural/functional alterations in the S-S anastomosis may contribute to increased abdominalpain in S-S CD pts 2 years after surgery.

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Long-Term Clinical Outcomes Following Surgery in Crohn's Disease Patientson Combination Immunosuppression: Impact of Anastomotic Reconstructionon Quality of Life and Healthcare UtilizationDaniel Stein, Yelena Zadvornova, Emery C. Lin, Amar S. Naik, Lilani P. Perera, NandaVenu, Mary F. Otterson, David G. Binion

Introduction: The majority of Crohn's disease (CD) patients will require ileal-cecal resection,and reconstruction will use either a hand sewn end-to- end (ETEA) or stapled side-to-sideanastomosis (STSA; "functional end-to-end"). STSA has the advantages of faster constructionand lower anastomotic leak rates. However, stapling devices transect the circular musclelayers interrupting propulsive contractions and the anti-peristaltic orientation of the side-to-side bowel further disrupts motility, creating a "pouch-like" intestinal structure. Thisprinciple of anti-peristaltic side-to-side orientation and transection of circular muscle layersis intentionally used during J pouch formation to improve fecal continence by preventingperistalsis, creating a reservoir for stool. We hypothesized that STSA will contribute to fecalstasis, abdominal pain and poor quality of life in CD, while the ETEA avoids circular muscletransection and pouch formation and will restore intestinal physiology leading to betterlong-term outcomes. Methods: A retrospective review of a prospectively collected IBD data-base from 1/1998 to 9/2011 identifying CD patients with IC resections was performed.Anastomosis type was determined and patients with ETEA or STSA were then analyzed forCD phenotype, mean SIBDQ, HBI, colonoscopies, hospitalization, repeat surgery, laxativeuse, constipation, and immunosuppressant use since their operation. Results: A total of 229(65% F) pts were included, 70 with STSA and 159 with ETEA. There was no difference inage, gender, smoking, or race. Mean follow up was 4.8 and 6.7 years in the ETEA andSTSA, respectively (p=0.0001). ETEA had a greater proportion of stricturing (61.0% vs48.5%,p=0.005) and fewer inflammatory (3.7% vs. 15.2%, p=0.005) type patients thanSTSA group. During post-op follow-up the ETEA group had better quality of life (meanSIBDQ 52.2 vs 46.8 p=0.002) and lower disease activity (mean HBI 2.6 vs 3.6 p=0.03) thanthe STSA group. Additionally, the STSA group required more colonoscopies (2.2 vs 1.6, p=0.01), hospitalizations (0.9 vs 0.4 p=0.002), and surgeries (1.2 vs 0.48 p=0.0001) than theETEA. On a per year basis, ETEA compared to STSA showed: hospitalization rate (0.08 vs0.17 p=0.03), surgery rate (0.1 vs. 0.2 p=0.08) and colonoscopy rate (0.4 vs 0.4 p=0.9).The mean CRP trended higher in the STSA group (1.1 vs. 0.7, p=0.10). Both groups hadhigh rates of combination immunosuppressive therapy, (91.8 and 97.4 p=0.2). Conclusions:In the present era of immunosuppressive therapy, STSA following ileal-cecal resectionadversely impacts long-term health related quality of life and healthcare utilization comparedto ETEA in CD when patients are followed beyond 1 year. Our results differ from priorstudies due to the multi-year follow-up and high rates of medical treatment in the post-optime period.

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Unveiling the Black Box: GI Manifestations of Behcet's DiseasePreet Bagi, Meghna Alimchandani, Martha Quezado, Aradhana Venkatesan, CindyPortner, Elizabeth Joyal, Cailin Sibley, Theo Heller

PURPOSE Behcet's disease is a chronic, systemic relapsing rheumatologic disorder ofunknown etiology. It manifests primarily with oral and genital ulcers, uveitis, cardiovascularand neurologic vascular abnormalities. We aim to describe the GI manifestations of thisdisease. METHODS 33 patients with an established diagnosis of Behcet's disease wereevaluated at the National Institutes of Health under a prospective protocol. Data collectioninvolved a GI symptom questionnaire, laboratory data, endoscopic assessment (upper endos-copy, colonoscopy and video capsules), evaluation of endoscopic sedation requirements,review of radiologic studies and analysis of histopathologic data. RESULTS A prospectiveGI questionnaire performed on our 33 patients revealed a 94% prevalence of GI symptoms(31/33). Abdominal pain in 76% (25/33), chronic diarrhea in 52% (17/33), chronic constipa-tion in 48% (16/33), gastroesophageal reflux disease 42% (14/33) and blood per rectum in33% (11/33) were the most common GI symptoms. 15% (5/33) met criteria for irritablebowel syndrome. Endoscopic and video capsule findings were notable for erythema and/orulcers in the: esophagus in 8% (2/24), stomach 42% (10/24), duodenum 13% (3/24),jejunum 7% (1/15), terminal ileum 14% (3/21) and colon 29% (6/21). GI biopsies werenotable for vascular changes in 75% (138/184) including vascular congestion/ectasia, thrombiand ischemic-like colitis. The most common radiologic finding was solid stool throughoutthe entire colon in 81% (13/16). During endoscopy, most patients had significantly higheranesthesia requirements than expected. Monitored anesthesia care (MAC) 52% (12/23) orgeneral anesthesia (GETA) 35% (8/23) was provided and more than expected sedation wasrequired in the MAC group at 75% (9/12) and in 63% (5/8) of the GETA group. CONCLU-SION GI symptoms are extremely common in Behcet's patients. Endoscopy should beperformed to exclude GI ulceration in patients with select GI symptoms as this finding willalter management. Functional GI disorders may be difficult to differentiate from Behcet'scomplications in this population. When performing endoscopy on Behcet's patients, subjects

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