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The Short-Term Efficacy and Safety of Adalimumab in Crohn's Disease (CD)Patients- a Retrospective StudyIris Dotan, Daniel Rachmilewitz, Vardit Peles, Sigal Fishman, Ariela Bar-Gil Shitrit, JorgePfeffer, Stuart Becker, Guy Rozner, Revital Kariv, Zamir Halpern

Background: Anti TNF-α blockers are increasingly used in IBD. Good short and long termeffects were reported with infliximab. Adalimumab is a fully humanized anti TNF-α antibodywith reported efficacy in remission induction and maintenance of CD in clinical studies.Only few post-marketing reports were published. Aim: To evaluate short-term efficacy andsafety of adalimumab in the treatment of active CD. Methods: Demographic and clinicalinformation as well as adverse events (AE) were retrospectively recorded for patients treatedwith adalimumab for at least 1 month. Treatment regimen was identical for all patients-160 mg at week 0, 80 mg at week 2 and 40 mg every other week since week 4. Results:Forty patients with active CD were included, 21 females, average age 37.7±16.6 years.Disease duration was 12.2±10.6 years. Forty percent of the patients had inflammatory diseasebehavior, 30% penetrating, and 30% stricturing. A third was past or present smokers.Twenty-five patients (62%) were previously treated with infliximab. The major reason forstopping previous infliximab treatment was loss of response. CDAI was 383±114 at baselineand 169±108 after 3 months of adalimumab treatment (n=21, p<0.001). Moreover, remissionat 3 months was 50% and in 80% a 100-point decrease in CDAI was observed. The short-term effect of adalimumab in post infliximab patients was slightly lower compared to biologic-naïve patients. Fifteen patients (37%) had AE. Injection site reactions in 4, vomiting andabdominal pain in 3, flu like symptoms in 3, headache and dizziness in 3, hypertension in1 and hematuria in 1. There were no short-term infectious complications. Eight patients(20%) stopped adalimumab treatment-5 due to non-response and 3 due to AE (headache,hematuria and hypertension). Fifty percent of the patients who had AE to infliximab alsohad an AE to adalimumab. Patients treated with concomitant immunomodulators (n=8) orconcomitant steroids and immunomodulators (n=4) had better clinical response at 3 monthscompared to those on concomitant steroids alone (n=5) (75, 75 and 20%, respectively, p=0.22). Conclusions: Adalimumab is an effective short-term treatment for active CD. Patientsnaïve to biologic treatments seem to have better short- term response to adalimumab.Concomitant immunomodulators contribute to treatment efficacy. A fifth of the patientsstopped treatment due to no response or side effects. Thus, a need for additional treatmentstrategies and preparations still exists.

W1151

Long Term Evaluation of Safety and Effectiveness of Infliximab Therapy inStenosing Crohn Disease After Endoscopic Pneumatic DilatationAlessandro Gigliozzi, Sandro Boschetto, Maurizio Giovannone, Mauro Tosoni, NadiaPallotta, Enrico Corazziari, Fausto Barberani

BACKGROUND:Anti-TNF treatment(Infliximab-IFX)has changed medical therapy of CD andis routinely used in patients with fistulazing CD and in those refractory to other treatmentsbut its role in stenosing CD is still controversial,because of its hypothetic fibrogentic effectrelated to accelerated healing processes; otherwise endoscopic pneumatic dilatation(EPD)avo-ids surgery only in about 50% of these patients and frequently with relapses of stenosisand/or no complete symptoms release.Our previous data (Barberani F. et al Gastroenterology2006,130-4 supp.2,W1206)provided first evidence of safety and effectivness of anti-TNFtherapy in patient with stenotic CD previously treated by EPD.AIM:to evaluate long termfollow up of same pts with stenotic CD treated by EPD+IFX combined therapy previouslydescribed. METHODS:between 2002 and 2005 10 pts previously described(moderate/severedisease-CDAI>250,with unique and<8 cm length ileal/ileocolic stenosis,5/10 with anamnesticreport of previous ileocolic surgery for stenosis CD)underwent to EPD successfully performedfollowed by IFX therapy 5mg/kg conventional scheduled every 8 weeks;these patients wereroutinely monitored every 8 weeks and by endoscopic and small intestine contrast ultrasonog-raphy(SICUS)evaluation every year.RESULTS:median follow up is 65±12 months.3 pts havea follow up between 48 and 60 months,4 between 60 and 72 months and 3 >72 months.7/10treated pts maintained optimal and other medical treatments-free clinical response previouslyreported,with no stenosis at endoscopic and SICUS follow up;one of this 7 patients,with81 months of follow up,stopped IFX after 73 months for drug-sensibilization and startedAdalimumab maintaining clinical and endoscopic remission.3 pts underwent surgical resec-tion,all with evidence of clinical and endoscopic relapse:first patient,moving to an anothercity,stopped IFX at 33 months of follow up because of partial loss of response and presentedendoscopic evidence of terminal ileum stenosis at 48 months;second patient presentedmultiple ileal stenosis at 50 months of follow up with high grade of mucosal inflamma-tion;third patient presented mild stenosis of terminal ileum at 33 months of follow upwith endoscopic and SICUS evidence of ileal inflammation relapse.CONCLUSION:Optimalclinical response and specifically the absence of stenosis during long term follow up of 7/10 of our pts provides evidence of high effectivness of anti-TNF therapy also in stenoticCD initially treated by EPD.Otherwise our data suggest that failure of these combinedtreatments is more related to loss of anti-inflammatory properties of biological drug thanaccelerated healing processes

W1152

Silent Crohn's Disease (CD): Poor Correlation Between Crohn's DiseaseActivity Index (CDAI) and Endoscopic Activity Scores One Year AfterIntestinal Resection and Ileocolonic AnastomosisMiguel Regueiro, Wolfgang H. Schraut, Kevin Kip, Leonard Baidoo, Scott E. Plevy, JosephF. Rodemann, Antonia R. Sepulveda, Marilyn Pesci, Janet Harrison, Andrew R. Watson,David G. Binion

Background: Following intestinal resection, most CD patients do not manifest signs orsymptoms of intestinal inflammation. Ability of CDAI and serum markers to assess post-operative endoscopic CD activity is not known. Aims: To assess the concordance betweenendoscopic activity scores and CDAI, C-Reactive Protein (CRP), Sedimentation Rate (ESR),

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and histology activity scores in CD pts 1 yr after intestinal resection and ileocolonic anastom-osis. Methods: Concordance of endoscopic and clinical CD activity was assessed as part ofa 1 yr post-operative prevention study. 24 CD pts were randomized to infliximab or placeboafter intestinal resection. All had a colonoscopy 1 yr later to assess for CD recurrence.Endoscopic CD activity in the neoterminal ileum was scored: i0=normal neoTI, i1=1-5aphthous ulcers, i2= >5 ulcers, i3=diffuse ileitis, and i4= large ulcers and/or narrowing.Endoscopic remission was defined as i0 or i1 and endoscopic recurrence as i2, i3, or i4.Clinical recurrence was defined as CDAI > 200 and remission as CDAI < 150. Biopsies werescored for histological activity: 0=inactive, 1-3=minimally active, 4-6=mildly active, 7-10=moderately active and 11-14=severely active. Normal ESR and CRP were 0-20 mm/h and0-0.8mg/dl, respectively, with values above the upper limit indicating inflammation.Results:At the end of 1yr, 12 pts had endoscopic remission (i0 or i1) and 12 had recurrence (i2,i3, or i4). There was strong concordance between endoscopic and histological activity: meanhistology score of 1.42 in pts with i0,i1 vs 6.92 in pts with i2, i3, i4, p<0.0001. There wasno concordance between endoscopic activity and the CDAI; mean CDAI of 134+52 in ptswith scores of i0,i1 and an identical mean CDAI of 134 + 121 in pts with i2,i3,i4, p=0.99.Among the 14 pts with a CDAI <150, there was no association with endoscopic remission:6 pts (54.5%) with i0, i1 and 8 pts (66.7%) with i2, i3, or i4, p=0.68. Among the 5 ptswith a CDAI >200, there was only weak concordance with endoscopic recurrence: 1 pt(9.1%) with i0, i1 and 4 pts (33.3%) with i2, i3, i4, p=0.32. There was no concordancebetween endoscopic activity and ESR/CRP levels; mean ESR of 25.5 mm/h and mean CRP0.67+0.82 mg/dl in pts with endoscopic scores of i0, i1 compared with ESR 22.8 mm/hand CRP 1.18+1.58mg/dl in pts with i2,i3,i4 (p=0.85 and p=0.18, respectively).Conclusion:The CDAI and ESR/CRP correlate poorly with endoscopic and histological post-operativeCD activity. Due to a high rate of silent CD recurrence in the first postoperative year,endoscopic assessment is a more sensitive parameter of inflammatory disease activity thanCDAI.

W1153

The Utility of Urinary Prostaglandin E-M (PGE-M) As a Biomarker of Crohn'sDisease ActivityBrad Maltz, Ginger Milne, James C. Slaughter, Nipun Merchant, David A. Schwartz

INTRODUCTION Available clinical measures of Crohn's disease (CD) activity can be overlyinfluenced by functional symptoms. Cyclooxygenase-2 (COX-2) is involved in prostaglandinE2 (PGE2) synthesis and is expressed in epithelial inflammatory conditions and some cancers.We have developed an assay to quantify the major urinary metabolite of PGE2, PGE-M.Prior studies have shown PGE-M to be significantly elevated in patients with IBD relativeto controls. We have previously shown a correlation between urinary PGE-M levels and UCdisease activity. The purpose of this study was to compare the PGE-M as a measure of CDdisease activity. We also looked at other disease biomarkers (CRP and Fecal Calprotectin)in a smaller cohort of patients with CD (n=35; comparison cohort). METHODS 159 patientswith a known CD were prospectively enrolled. Disease activity was assessed using the HarveyBradshaw Index (HBI) and disease activity/location on endoscopy was noted. (ileitis, colitis,proctitis, or normal). Urine specimens (all patients), stool for fecal calprotectin, and bloodfor C-reactive protein (comparison cohort) were collected at time of enrollment. Urine PGE-M levels (ng/mg Cr) were determined by mass spectroscopy. Significance assessed usingKruskal-Wallis and Spearman tests. RESULTS There was no significant association with HBIand PGE-M (p=0.126) nor with HBI and disease activity or location (p=0.31). There wasno significant association with HBI and CRP (p=0.506) or fecal calprotectin (p=0.531). PGE-M was significantly associated with the presence of colitis on colonoscopy. Median [m] PGE-M in normal exams 9.5 (n=68), isolated ileitis 9.4 (n=39), diffuse colitis 28.6 (n=21) andproctitis 10.9 (n=30) p=0.001. When Crohns colitis was compared to the other three groups,[m] PGE-M was 28.6 (colitis) vs. 10 (others) p<.001. In the comparison cohort (n=35),fecal calprotectin was found to be significantly associated with active colitis [m] 442 (n=14) and proctitis 183 (n=4) but not isolated ileitis 66 (n=9) or normal 63 (n=8) p<0.002.CRP was found to be associated with ileitis [m] 8 (n=9) and colitis 6.1 (n=14) comparedto proctitis 1.7 (n=4) and normal 2.9 (n=8) p<0.036. CRP and calprotectin were correlatedr=0.43 (p=0.01). CONCLUSION Urinary PGE-M correlates significantly with active CDcolitis seen at endoscopy. Urinary PGE-M did not correlate with overall disease activity asmeasured by the HBI. HBI was not associated with disease activity or location of disease asseen on endoscopy. This study shows that urinary PGE-M is not a useful biomarker for theaverage CD pt but may be a more useful biomarker for patients with isolated colitis.

W1154

Non-Invasive Imaging of Transmural Inflammation in Crohn's Disease UsingMicrobubble Contrast Enhanced UltrasonographyLotte C. Dinesen, Edward Leen, Subrata Ghosh

Background: Crohn's disease of the gastrointestinal tract is characterized by segmentaltransmural inflammation and typically runs a chronic relapsing and remitting course. Sincemost patients with Crohn's disease require frequent evaluation, there still is a need for areliable, non-invasive, easily accessible test for determining disease activity as these patientsare often young. There is early evidence to suggests that using transabdominal ultrasoundenhanced with encapsulated gaseous microbubbles (CEUS) may provide such a means todetect and quantify the degree of intestinal inflammation. These gas filled bubbles can besafely injected intravenously to enhance an ultrasound scan. In a pilot study the role ofSonovueTM Contrast-enhanced ultrasonography (CEUS) was assessed as a diagnostic toolin patients with IBD. Materials and Methods: 13 patients were studied; 10 active Crohn'sdisease (CD) patients,on Anti TNF alpha and/or on immunosuppressive treatment, and 3quiescent CD. CEUS was performed in all cases using IU22 scanner with L12-9 and V6-2probes using standardized protocol at low out-put power; 2ml of SonoVue was administeredas an iv bolus and data acquired was recorded digitally to be analysed using Qlab quantifica-tion software.From the intensity time curves derived from regions of interest on the bowelwall, mesenteric artery and subcutaneous fat layer, the following parameters were calculated:Time to peak is a measure of speed of flow (TP), peak intensty is a measure of the vascularvolume (PI); Ratio of bowel to mesenteric artery TPs is used to normalise for any differences

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