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Re-Introduction of Infliximab After Consecutive Failure of Infliximab andAdalimumab Is Beneficial in Refractory Crohn's DiseaseJohannan F. Brandse, Charlotte P. Peters, Emma J. Eshuis, M. Lowenberg, CyrielPonsioen, Gijs R. van den Brink, Geert R. D'Haens

BACKGROUND In the last decade, Infliximab (IFX) and Adalimumab (ADA) have dramati-cally improved the management of steroid refractory Crohn's disease (CD). In clinical practicea considerable group of patients are switched from one agent to the other because of failure,intolerance and patient preference. There are no data regarding the long term clinical responseof re-exposure to IFX in patients who sequentially used and discontinued IFX and ADA.Therefore we retrospectively assessed clinical response to IFX in CD patients that failedsubsequently IFX and ADA and were re-exposed to IFX. METHODS For this survey weused a multicenter North-Holland cohort of 438 CD patients treated with ADA. Twenty-nine of these had previously been treated with IFX and received a second IFX treatmentafter failing ADA. Short-term and prolonged response to IFX was assessed retrospectivelyby reviewing clinical records. RESULTS 29 patients (62% luminal CD, 7% fistulizing CD,31% both) from 8 hospitals were included with complete follow-up data up to 18 months.IFX was re-started at 5mg/kg in 20/39 (69%), 7.5 mg/kg in 1 patient and at 10 mg/kg in8/29 (28%), at intervals varying between 4 and 8 weeks. Dose escalation was done in 8/29(28%) of patients during retreatment with IFX. Twenty patients (69%) were on concomitantimmune modulators at the re-introduction of IFX and 3 (10%) patients experienced adverseevents: acute infusion reaction (n=2, 7%) and delayed hypersensitivity reaction (n=1, 3%).Clinical response is shown in figure 1: 20/29 (69%) patients were still on continued Infliximabtherapy after 18 months. Reasons for discontinuing the second Infliximab therapy included:non-response (n=2, 7%), loss of response (n=3, 10%), intolerance (n=3, 10%) or non-compliance (n=1, 3%). CONCLUSION The majority of CD patients, failing prior treatmentwith IFX and ADA, benefit from re-introduction of Infliximab for at least 18 months. Onlya small proportion of 9 patients failed on retreatment with IFX. Retreatment with Infliximabis to be considered a valuable strategy in this group of refractory CD patients.

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Parietal Healing in Patients With Crohn's Disease on Maintenance TreatmentWith BiologicsFabiana Castiglione, Anna Testa, Matilde Rea, Giovanni D. De Palma, Maria Diaferia,Dario Musto, Francesca Sasso, Nicola Caporaso, Antonio Rispo

Introduction: Crohn's disease (CD) is usually treated by thiopurines and anti-TNF alphaagents in presence of steroid-dependency and prognostic factors of disabling disease suchas perianal fistulising complications and extra-intestinal manifestations. Mucosal healing(MH) is a crucial end-point in CD patients, being a predictor of a lower need for steroids,hospitalizations and surgery in the following years. Conversely, data about parietal healing(PH) after therapy with traditional immunosuppressors and anti-TNF alpha agents are stilllacking. Aim of this study was to explore the rate of PH in CD patients treated with biologicsand immunosuppressors and its correlation with clinical remission (CR) and MH. Methods:In the period comprised between April 2008 and June 2012 we performed an observationallongitudinal study evaluating PH, CR and MH in all CD patients on maintenance treatmentwith biologics or thiopurines for at least 2 years. Steroid-free CR was defined in accordancewith ECCO guidelines. MH was assessed by using SES-CD while PH was recorded by usingbowel sonography (BS). All patients performed endoscopy and bowel sonography beforestarting therapy and 2 years later. Results: The study included 66 CD patients treated bybiologics and 67 patients receiving thiopurines. After 2 years of therapy, PH were evidentin 17 patients on biologics and only 3 subjects treated by thiopurines (25% vs 4%;p,0.01;O.R.=6.2). CR was achieved in 37 patients (59.7 %) on biologics and in 34 patientson thiopurines (59.7% vs 53%; p=n.s.) while MH was more frequent in patients treated byanti-TNF alpha agents even if not reaching statistical significance (38% vs 25%; p=n.s.).The mean SES-CD score and the bowel wall thickness (BWT) at BS decreased significantlyonly in patients treated by biologics (SES-CD 11.1 vs 8.9 +2.7; p=0.001; BWT at BS 6.0 vs4.0 +0.9; p, 0.01). Conclusions: Parietal healing can be achieved in about 25% of patientswith Crohn's disease treated with anti-TNF alpha agents. Further studies are needed todefine the potential role of parietal healing as long-term prognostic factor.

S-776AGA Abstracts

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Predictive Factors for Mucosal Healing in Crohn's Disease Patients WithUnelevated Serum CRP LevelsAsuka Nakarai, Sakiko Hiraoka, Jun Kato, Toshihiro Inokuchi, Mitsuhiro Akita, TomokoHirakawa, Keisuke Hori, Keita Harada, Hiroyuki Okada, Kazuhide Yamamoto

Background & aims: Accumulating evidence has underlined the importance of mucosalhealing (MH) as a treatment goal of Crohn's disease (CD). Evaluation of MH in CD is ratherdifficult because CD can involve entire gastrointestinal system, particularly the small bowel.In general, endoscopy including colonoscopy, capsule endoscopy, and balloon enteroscopy,and/or radiologic modalities including computed tomography, magnetic resonance imagingand fluoroscopy are necessary. In addition, repeated examinations with such modalities arerequired during a long-term disease course. Therefore, predictive factors for MH in placeof imaging techniques are desirable. Serum C-reactive protein (CRP) levels are one of thecandidates for this purpose. However, it has previously been reported that CRP levels donot elevate in 20-30% of active CD patients despite presence of disease activity. The aimof this study is to determine predictive factors for MH in CD patients without elevation ofserum CRP levels. Methods: A total of 128 CD patients of whommucosal status was evaluatedby performing endoscopic and/or radiologic modalities were included in this study. Patientswere divided into two groups according to serum CRP levels: CRP , 10 mg/L and . 10mg/L. The correlation between presence of MH and values of clinical variables includingCDAI, leukocyte count, platelet count, hemoglobin, serum albumin, CRP, and total choles-terol were examined in the low CRP (, 10 mg/L) group, and predictive factors for MH inthose patients were explored. Results: Of 128 patients, 33 were included in the high ( . 10mg/L) CRP group, whereas 95 were in the low CRP group. All but one in the high CRPpatients showed mucosal active inflammation, while in contrast, 41 (43%) of 95 low CRPpatients manifested MH (p , 0.0001, chi-square test). In the low CRP patients, presenceof MH was correlated with CDAI, hemoglobin, platelet count (PLT), and serum CRP andalbumin. Multivariate analysis revealed that CDAI , 115 and PLT , 330000/μl weresignificant predictive factors for MH in the low CRP patients (CDAI , 115, OR = 4.66;95%CI, 1.36-17.83, p = 0.014,PLT , 330000 /μl, OR = 5.04;95% CI, 1.62-17.99, p = 0.0047).Fulfillment of these two criteria predicted MH with 0.78 (95% CI, 0.67-0.86) sensitivity,0.74 (95% CI, 0.66-0.80) specificity, and 0.76 (95% CI, 0.66-0.83) accuracy in the lowCRP patients. Conclusion: MH could be predicted noninvasively by using CDAI and plateletcount in CD patients with unelevated serum CRP levels.

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Mucosal Healing Without Endoscopic Activity Predicts Long-Term ClinicalRemission in Patients With Ulcerative ColitisNagamu Inoue, Kaoru Takabayashi, Tetsuro Takayama, Katsuyoshi Matsuoka, MakotoNaganuma, Tadakazu Hisamatsu, Yuichiro Hayashi, Takanori Kanai, Haruhiko Ogata,Yasushi Iwao, Toshifumi Hibi

INTRODUCTION: Mucosal healing (MH) has emerged as not only an endpoint in clinicaltrials but also a desirable treatment goal in clinical practice in patients with ulcerative colitis(UC). However, the role of MH on long-term disease outcomes has been evaluated in veryfew studies and whether MH includes endoscopic mild activity, which corresponds to Mayoendoscopic score 1, remained obscure. Therefore, in the present study, we explored theassociation of endoscopic activity of patients in clinical remission with their long-term clinicaloutcome. METHODS: We conducted a retrospective cohort study in clinical practice at asingle center. Among 724 UC patients who underwent colonoscopy between in November2007 and December 2008 at our hospital, 331 patients in corticosteroid-free clinical remissionwere enrolled. Demographics, clinical data, endoscopic activity, histological activity andclinical outcome after colonoscopy for at least 2 years were collected from medical records.Clinical relapse was defined as increase in bowel movement plus reappearance of rectalbleeding at 2 consecutive visits. Endoscopic activity was graded according toMayo endoscopicscore by findings of white light images. Association between variables and clinical relapsewas evaluated by univariate and multivariate analyses using Cox regression model. Cumula-tive non-relapse rate was calculated using Kaplan-Meier survival analysis and comparedamong groups using log-rank test. RESULTS: The median follow-up was 39 (range 24-49)months. Overall, 69 (20.8%) patients relapsed, after a median latency of 16 (range 0-43)months. The cumulative relapse rate was 8.3, 15.5, 20.5 and 22.3% at 1, 2, 3 and 4 years.Mayo endoscopic score 1 (hazard ratio (HR): 2.86) and score 2 (HR: 3.60) was significantrisk factor for clinical relapse against endoscopic score 0 (Table). Univariate analysis alsoidentified significant association with relapse for moderate clinical activity of last flare,remission induction with cytapheresis (CAP), maintenance with imuunomodulator, shorterduration of remission and higher histological activity. Cox regression analysis after adjustmentof possible confounding factors revealed that endoscopic activity, histological activity, dura-tion of remission and remission induction with CAP were found to be independent determi-nants of relapse. For endoscopic activity, HR of score 1 was 2.08 to score 0 (p=0.017) butHR of score 2 was 1.01 to score 1 (not significant) (Table). Finally, the Kaplan-Meierestimate of non-relapse rate by endoscopic activity groups demonstrated significant difference(p,0.001). While there was significance between score 0 and 1, there were no significancebetween score 1 and 2 (Figure). CONCLUSION: The present study demonstrated thatendoscopic remission (Mayo endoscopic score 0 other than score 1) predicted long-termclinical remission in UC.Risk of relapse analyzed by the Cox proportional hazard model