(ATA), which are associated with lower ADA serum levels and treatment failure. The aimof this study was to assess the degree of correlation of serum ADA and ATA levels withindices of serologic and endoscopic mucosal inflammation in patients with inflammatorybowel disease (IBD). Methods: We designed a cross-sectional study including patients 18years or older with CD or UC on treatment with ADA. Predictive variables included weredemographics, disease phenotype, concurrent use of immunosuppressive drugs (mercapto-purine, azathioprine or methotrexate) and/or steroids, and random ATA/ADA levels (mea-sured using a validated non-radiolabeled homogeneous mobility shift assay by PrometheusLaboratories [San Diego, CA]). The primary outcomes were the presence of macroscopicmucosal inflammation (MMI) during endoscopic exam and C-reactive protein (CRP) level.Results: 66 patients were included; 59 had CD. 62 (94%) and 18 (27%) of IBD patientshad detectable ADA and ATA, respectively. A minimum ADA cutpoint of 5 μg/mL bestpredicted elevation of CRP levels (ROC: 0.71). The mean ADA level was significantly higherin patients with undetectable ATA that in those with ATA (12.5 vs 5.7 μg/mL respectively,p=0.001). Mean ADA levels were higher in patients with mucosal healing than in thosepatients with MMI (13.3 vs 8.5 μg/mL, respectively, p=0.02). The mean serum CRP levelwas significantly higher in those patients with detectable ATA than those lacking ATA (12vs 2.1 mg/dL respectively, p=0.002). Detectable ATA was associated with ADA ,5 μg/mL (OR 8.6 [95%CI:2.3-31.8;p,0.001], MMI (OR 3.8 [95%CI:1.1-13.2;p=0.03], need forsteroids (OR 3.7 [95%CI:1.1-12.9;p=0.03], and previous infliximab use (OR 3.9 [95%CI:1.0-15.2;p=0.04]. When compared to those patients prescribed ADA monotherapy, patientscombining ADA therapy with an immunomodulator had a higher mean level of ADA (9 vs14 ug/mL, respectively, p=0.026). Conclusions: Among patients with IBD, serum ADA andATA levels correlate well with both serologic and endoscopic inflammatory activity. An ADAlevel ≥5 μg/mL correlates well with lower CRP, and combination therapy with immunosup-pressive drugs improves serologic levels of ADA. Further work establishing the role ofmeasuring ADA and ATA levels in clinical care are warranted.

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Mechanisms of Loss of Response to Adalimumab in Crohn's DiseaseDouglas C. Wolf, Scott Hauenstein, Steven Lockton, Sharat Singh

Anti-TNFα agents, such as adalimumab (ADA), used for the treatment of IBD are effectivein reducing disease activity in patients and offer significant benefits in quality of life. Lackof response to ADA is likely due to three scenarios: low serum drug levels, anti-drug antibodygeneration, or an alternative mechanism not driven by TNF α. Serum ADA and antibody-to-adalimumab (ATA) levels, along with cytokine profiles, were studied in Crohn's Diseasepatients who had lost response to ADA treatment to evaluate the mechanism of loss ofresponse. Methods:: Approximately 25 sites participated in an IRB approved, single visitstudy of subjects treated with ADAwho initially achieved response/remission and experiencedloss of response to treatment. Subjects must have been on ADA for ≥3 months and havedemonstrated an initial response to ADA as assessed by global assessment or HBI. Wecollected serum samples from 49 Crohn's Disease patients and tested for serum levels ofATA and ADA using the HMSA as previously described (Wang, 2012). Briefly, serum samplesand calibrators were mixed and incubated with the labeled antigen. The immune complexesformed and the free label were separated and quantitated by a SEC-HPLC system equippedwith a fluorescent detector. Serum samples were also tested for inflammatory cytokinesusing proprietary methods. Results: 42/49 patients (86%) had detectable ADA (.0.68 μg/mL) with a median serum concentration of 7.2 μg/mL and a range of 0.73-31.54 μg/mL,while 23/49 patients (47%) had detectable ATA (.0.55 U/mL). Of the seven patients withundetectable ADA, 6 had detectable ATA, and 17 of the 42 ADA detectable patients werealso ATA+ (O.R. = 0.118, p = 0.041). ADA levels were inversely associated with the levelof ATA generation (median ADA for ATA- samples = 9.78 μg/ml; median ADA for ATA+samples = 4.9 μg/ml, p = 0.022). 26/49 patients (53%) had less then 8 μg/mL ADA, athreshold concentration above which has been associated with the best efficacy (Karmiris,2009; Table 1). 15 of these patients had detectable ATA, leaving 11 patients who hadsubtherapeutic levels of ADA for other reasons. Of the 23 patients with greater than 8 μg/mL ADA, 8 had detectable ATA (35%). The remaining 15 patients likely lost response dueto an alternative mechanism. Several patients demonstrated cytokine profiles that suggestactivation of alternative pathways that could be a reason for loss of response. Conclusions:Analysis of ADA and ATA levels in patients losing response showed a high incidence ofATA generation. ADA levels were inversely associated with the level of ATA generation. Thisstudy presents evidence that loss of response can result from low drug levels, ATA production,or alternate pathways.Table 1

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Appropriateness of Laboratory Testing in IBD Inpatients - An Opportunity toReduce Unnecessary Healthcare CostsAoibhlinn M. O'Toole, Mary Forry, Gavin C. Harewood, Frank E. Murray, StephenPatchett

Introduction: The nature of Inflammatory Bowel Disease (IBD) renders patients susceptibleto disease flares necessitating hospital admission. ECCO guidelines recommend baselinelaboratory testing [electrolytes (U/E), C-reactive protein (CRP), liver enzymes, and completeblood count (CBC)] should be performed on admission and thereafter as clinically indicated.Additionally NICE guidelines highlight the increased risk of refeeding syndrome in IBDpatients and advocate electrolyte (Ca, Mg, PO4) measurement. Although testing of theseparameters is recommended on admission, frequency of subsequent testing is guided bywhether baseline values are normal/abnormal. The aim of this study was to characterize theutilization of laboratory testing in our inpatient IBD cohort and to describe the findings onserial testing of laboratory parameters. This allowed us to comment on the appropriatenessof laboratory testing in these patients. Methods: All patients hospitalized with a primarydiagnosis of IBD between January 2008 and December 2009 were identified using thehospital's inpatient computerized data system. The frequency of laboratory tests performedin this cohort of patients was analyzed. Results: In total, 57 patients were admitted with aprimary diagnosis of IBD during the study period; mean length of stay was 6.7 days. Asshown in the table, most patients underwent appropriate laboratory testing. Apart from CBCvalues and U/E values, which subsequently became abnormal in 35% and 20% of patients,laboratory values rarely became abnormal in patients with normal baseline indices. Despitethis, laboratory testing was performed with similar frequency irrespective of whether initialvalues were normal/abnormal. Conclusions: In patients hospitalized for IBD, non-CBC labora-tory tests rarely became abnormal following a normal index value. Laboratory testing appearsto be overutilized in these patients with little difference in frequency of testing in thosepatients with normal/abnormal baseline results. Improving physician awareness of the needto avoid excessive testing in patients with normal index values may reduce unnecessaryinpatient healthcare costs.

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Association of Serum Infliximab and Antibodies to Infliximab to Long-TermClinical Outcome and Mucosal Healing in Crohn's DiseaseOfer Ben-Bassat, Anna Romanova, Anna Iacono, Sue P. Irwin, Gordon R. Greenberg

Background/Aims: Infliximab (IFX) is effective therapy for Crohn's disease (CD). Previousstudies have shown that formation of antibodies to infliximab (ATI) is associated with lowertrough serum IFX levels and loss of clinical response. However, solid phase ELISA assaysare limited by the inability to detect ATI in the presence of circulating drug. We evaluatedthe relationship between trough serum IFX and ATI formation to long-term clinical outcomeand mucosal healing in CD using a fluid phase assay that simultaneously detects drug andATI. Methods: In a cohort of 234 patients with active CD treated with 5 mg/kg IFX inductionfollowed by maintenance therapy, rates of steroid-free clinical remission (Harvey-BradshawIndex ≤2), endoscopic remission (no mucosal ulcers at follow-up colonoscopy n = 160)and normalization of CRP (, 5ug/L) were assessed in relation to the presence or absenceof detectable trough serum levels of IFX with or without ATI formation. Serial serum sampleswere drawn prior to maintenance infusions and concentrations of IFX and ATI subsequentlymeasured by an HPLC-based fluid phase assay (Prometheus Laboratories, San Diego CA).Results: After a median follow-up of 66.9 months (IQR: 31.9-98.8), 155 patients had adetectable trough infliximab, of whom 57.7% were IFX+/ATI- and 8.5% were IFX+/ATI+.Among 79 patients with undetectable infliximab 9.4% were IFX-/ATI- and 24.4% IFX-/ATI+. ATI formation was higher after interrupted compared with scheduled maintenancetherapy (37.1% vs.20.5% P=0.027). A serum infliximab . 2ug/ml was associated with higherrates of steroid-free remission (93.3% vs.36.7%), endoscopic remission (50.9% vs.7.8%) anda lower CRP (2.5 vs.14.5 ug/L) (all P,0.001). Amongst patients who were IFX+/ATI+ clinicaloutcomes and median serum IFX were not different compared with the IFX+/ATI- group(7.6 ug/ml vs. 9.1 ug/ml) whilst median ATI titers were lower compared with IFX-/ATI+patients (8.9 U/ml vs.50.5 U/ml; P,0.001). ATI developed in 25 IFX+/ATI- patients ofwhom 17 became IFX+/ATI+ and 8 IFX-/ATI+; 17 had been interval shortened over thefollow-up and none were discontinued. Conclusions: For patients with active CD treatedwith infliximab, a detectable trough serum infliximab .2ug/ml is associated with sustainedclinical remission, mucosal healing and lower CRP. A threshold serum infliximab ≤2ug/ml,irrespective of ATI status, is associated with a less favorable outcome.

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