S282 Poster presentations

Conclusions: GA is a common cutaneous disorder presentingas annular groups of skin-colored to erythematous papules andassociated with diabetes mellitus, malignancy, thyroid diseaseand dyslipidemia. GA is not an extraintestinal manifestation ofIBD. There is just one case of Crohn’s disease associated withGA and with response to biological therapy.GA seems to be parallel to the activity of the bowel disease,and it’s important to the gastroenterologist the correctmanagement of these lesions.

P513Disparity between infliximab trough level andinfliximab associated adverse eventsV.W. Huang*, N. Dhami, D.K. Fedorak, C. Prosser, C. Shalapay,K.I. Kroeker, R.N. Fedorak. University of Alberta, Medicine,Edmonton, Canada

Background: Infliximab is an anti-TNF agent effective in themanagement of inflammatory bowel disease (IBD). However,patients frequently report infliximab-associated adverse events(AE) including skin rashes, arthralgias, neuropathy and infusionreactions. While these infliximab-associated AEs are well-documented their relationship to serum levels of infliximabhas not been evaluated. The aim of this study was to measurethe prevalence of infliximab-associated AEs in IBD patients anddetermine their relationship to infliximab trough levels.Methods: In this cross-sectional study of IBD patients oninfliximab, consecutive patients were recruited from theUniversity of Alberta IBD infliximab infusion clinic between 2012and 2013. Charts were reviewed for infliximab-associated AEs(defined as skin rashes, arthralgias, neuropathy and infusionreactions documented by 2 patient self-reports and/or onephysician report) at: (1) any time during the infliximabtreatment history or (2) immediately before or during theinfliximab infusion. Infliximab trough serum levels (ITL) wereobtained immediately before the infliximab infusion andmeasured using an in-house ELISA assay. Results are presentedas median ITL (range). Differences in median ITL were analyzedusing non-parametric Mann Whitney or Kruskal Wallis tests.Results: Of 87 consented patients, 12 were excluded due toinsufficient infusion records. Of the remaining 75 patients,36 (48.0%) had AEs at any time during their infliximab history,while 17 (22.7%) had AEs at the time of trough measurement.More females than males reported having had AEs at any time intheir infliximab treatment history (66.7% vs. 33.3%, p = 0.015).Otherwise there were no demographic variables associatedwith having AEs at any time in infliximab treatment history,or at the time of trough measurement. The median ITL wasnot significantly different between patients with and withoutAEs at the time of trough measurement [4.1 (0 19.5)mg/mLvs 7.3 (0 30.0)mg/mL, p = 0.091]. However, it was significantlyhigher in patients who reported dermatological AEs atthe time of trough measurement [9.9 (0.2 19.5)mg/mL vs.0.1 (0 6.3)mg/mL, p = 0.020], and significantly lower in patientswho reported infusion AEs at the time of trough measurement[0.4 (0 6.3)mg/mL vs. 9.9 (0 19.5)mg/L, p = 0.048].Conclusions: Nearly half of IBD patients on infliximab reportsome type of infliximab associated AEs over their infliximabtreatment history. A low infliximab trough level was associatedwith infusion reactions, while a high infliximab trough levelwas associated with dermatological AEs. This disparity suggeststhat these infliximab associated reactions may have differentpathological mechanisms that warrant further investigation.

P514Disease-specific health-related quality of life in adultpatients with mild to moderate ulcerative colitisreceiving short-term and long-term daily treatment withMMX mesalazineA.V. Joshi1 *, A. Yarlas2, M.K. Willian1. 1Shire, Health Economicsand Outcomes Research, Wayne, PA, United States, 2Optum,Life Sciences, Lincoln, RI, United States

Background: Symptoms (eg, rectal bleeding, stool frequency)experienced by mild-to-moderate ulcerative colitis (UC) pa-tients, negatively affect health-related quality of life (HRQL).These analyses examine the magnitude of improvements in UCpatients’ HRQL following short-term and long-term treatmentwith MMX mesalazine.Methods: Data were from a completed, open-label, prospec-tive, multi-country trial of mild-to-moderate UC patients(NCT01124149). In the acute phase, adults with active UCreceived 8 wks MMX mesalazine 4.8 g/d once daily (QD).Patients achieving complete remission (CR; modified UC DiseaseActivity Index [UCDAI] �1; rectal bleeding and stool frequencyscores of 0; �1-point reduction in endoscopy score) or partialremission (PR; modified UCDAI �3; combined stool frequencyand rectal bleeding score �1; not in CR) by Wk 8 subsequentlyreceived 12 mos of maintenance with MMX mesalazine 2.4 g/dQD.Patients’ HRQL (a tertiary endpoint), as impacted by UCsymptoms, was assessed with the Shortened InflammatoryBowel Disease Questionnaire (SIBDQ), a 10-item surveymeasuring inflammatory bowel disease (IBD)-specific HRQL overa 2-wk recall period. The SIBDQ has 4 domains: Bowel Symptoms(BS), Systemic Symptoms (SS), Emotional Function (EF), andSocial Function (SF). Total score is used to assess overall IBD-related HRQL. Higher SIBDQ scores indicate better HRQL.Changes over time were tested using paired-samples t-testsor repeated-measures analysis of variance models. Multiplicitywas controlled using Bonferroni-adjusted P values. Cohen’s dzeffect sizes for standardised differences in means for paired-samples were calculated to interpret magnitude of change.Results: Patients who completed the 8 wk acute phaseshowed significant improvement in all SIBDQ scores, with meanincreases of 4.5 points for BS (n = 425), 2.1 for SS (n = 442),3.6 for EF (n = 439), 3.0 for SF (n = 446), and 13.2 for totalscore (n = 413; all Ps <0.0001). Effect sizes for change wereall �0.77, with BS showing the largest improvement (dz = 1.16).Patients completing maintenance showed significant increasesin all SIBDQ scores from baseline to Mo 12, with mean increasesof 5.0 points for BS (n = 209), 2.6 for SS (n = 221), 4.6 for EF(n = 215), 3.6 for SF (n = 221), and 15.7 for total score (n = 198;all Ps <0.0001). There were no significant changes in any scoresfrom the end of the acute phase to the Mo 12 visit (all changes�0.5 points; all Ps >0.24).Conclusions: Patients with active mild-to-moderate UC showedsignificant, medium to large improvements in disease-specificHRQL following 8 wks of MMX mesalazine 4.8 g/d QD. Theseimprovements were maintained among patients in CR or PR whosubsequently received 12 mos of MMX mesalazine 2.4 g/d QD.

P515Disease-related knowledge in inflammatory bowel diseaseM. Eusebio *, P. Caldeira, A.L. Sousa, A. Giao Antunes, A.M. Vaz,H. Guerreiro. Centro Hospitalar do Algarve, Gastroenterology,Faro, Portugal

Background: Education of patients with inflammatory boweldisease (IBD) allows a greater understanding and acceptanceof their disease assuming a critical role in adherence andtherapeutic success. The aim of this study was to assessthe disease-related knowledge in IBD patients and to identifyfactors that can influence its acquisition.

Clinical: Therapy & observation S283

Methods: A questionnaire about disease (type, localization,diagnosis, treatment and surveillance) was distributed to IBDpatients who attended outpatient gastroenterology clinic atour Hospital. The answers were categorized as appropriate orinappropriate. Demographic data, education level and featuresof the disease were recorded.Results: 73 patients were included (41 females) with a meanage of 44 years-old and a mean duration of IBD of 9.4 years.There were 42 patients with Ulcerative Colitis, 29 with Crohn’sdisease and 2 with unclassified IBD. The mean of appropriateanswers was 53.6%. The type of IBD was correctly markedin 86% of patients whereas the specific localization of thedisease was recognized in only 27%. 95% of the respondersconsidered colonoscopy important in diagnosis. Only 55% of thepatients were aware of the increased risk of bowel cancer.A better performance in the questionnaire was associatedwith: younger patients at diagnosis (r = 0.593; p = 0.000)and at the time of the questionnaire (r = 0.451; p = 0.000),a higher education level (F = 5.976; p = 0.001), presence ofCrohn’s Disease (65% versus 46%, F = 6.990; p = 0.000), previoushospitalization (60% versus 42%, t = 4.197; p = 0.000) or surgeryrelated to the disease (66% vs 51%, t = 2.401; p = 0.019) andmultiple past medications (including 2 anti-tumor necrosisfactor therapy) (F = 4.194; p = 0.000).Conclusions: The age, the educational level of the patientand the severity of the disease requiring hospitalization,surgery or aggressive therapy, were associated with a betterknowledge of the disease. The low percentage (marginallypositive) of appropriate responses highlights the need forbetter educational strategies.

P516Discrepancy between fecal biomarkers and their intestinalgene expression in ulcerative colitis: Results from ananti-IL-13 antibody study

W. Reinisch1 *, J. Panes2, K. Page3, S. Khurana4, F. Hua3,G.M. Comer3, M. Hinz3, T. McDonnell Moorehead3,F. Cataldi3. 1Medical University of Vienna, InternalMedicine/Gastroenterology, Vienna, Austria, 2HospitalClinic I Provincial, Department of Inflammatory Disease,Barcelona, Spain, 3Pfizer Inc., Gastroenterology, Cambridge,United States, 4Premier Medical Group, Gastroenterology,Poughkeepsie, New York, United States

Background: IMA-638 is a humanized antibody that bindsand inhibits human interleukin 13 (IL-13). Elevated levelsof IL-13 transcripts have been found in rectal biopsies ofulcerative colitis (UC) patients and lamina propria mononuclearcells (LPMC) from UC patients secrete high titers of IL-13upon re-stimulation in vitro. In this study, we explored fecalcalprotectin (FC), lactoferrin, and YKL-40 as non-invasivebiomarkers for the evaluation of IMA-638 efficacy in UC. Allthree proteins are abundant in neutrophils and monocytes andare elevated in the stools of patients with UC.Methods: This was a double blind, placebo-controlled studywith patients 18 65 years of age with active UC (Mayo Score4 10) randomized to receive IMA-638 at one of 3 doses levels(200 mg, 400 mg, 600 mg) or placebo (P). The primary endpointwas fold change from baseline in FC at week 14 measuredusing a highly sensitive ELISA (Buhlmann Labs). Fecal lactoferrinand YKL-40 were measured using independent ELISAs (Techlab;R&D Systems) from the same homogenized stool samples. Theexpression of genes encoding calprotectin (S100A8, S100A9)and YKL-40 (CHI3L1) were measured on TLDAs using RNAextracted from colon biopsies.Results: The modified intent to treat population (mITT)included 84 patients with 21 patients/arm. At week 14, thesuperiority of 200, 400 and 600 mg compared to P in terms offold change of FC from baseline was not met. This result wassupported by a similar lack of effect seen in fecal lactoferrin

and YKL-40. The levels of all 3 proteins, at both baseline andweek 14, were well correlated to each other. FC and YKL-40proteins measured in the stool, however, did not correlatewith expression of their respective genes in inflamed colonbiopsies. The expression levels of S100A8, S100A9, and CHI3L1were increased in inflamed compared to non-inflamed biopsies,but did not change with treatment. No evidence of safety andtolerability concerns were noted and only a numerical trendwas observed in the efficacy parameters measured by the Mayoscore for the 200 and 400 mg doses but not for the 600 mgdose. Lastly, a statistically significant correlation was observedbetween FC and Total Mayo Score (p = 0.038).

Figure: Spearman correlations between (A) FC (x-axis) and fecal lactofer-rin (left) or YKL-40 (right) proteins and (B) FC and YKL-40 proteins andcorresponding genes.

Conclusions: This study was unable to confirm the effect ofIMA-638 after 14 weeks of treatment in patients with UC usingFC as a primary endpoint. This study, however, does not ruleout the use of fecal proteins in future studies as biomarkers ofefficacy in UC.

P517Discrepancy between efficiency and effectivenessof biological therapy in inflammatory bowel disease:EFIFECT study

D. Ginard1 *, S. Khorrami1 *, L. Perez-Carazo1, E. Tavío2,A. Lopez-Sanroman2, M. García-Alvaredo3, F. Munoz3,L. Ibanez4, I. Marín-Jimenez4, J. Guevara5, F. Casellas5.1Hospital Universitario Son Espases, Gastroenterology, Palmade Mallorca, Spain, 2Hospital Universitario Ramon y Cajal,Gastroenterology, Madrid, Spain, 3Complejo Hospitalariode Leon, Gastroenterology Unit, Leon, Spain, 4HospitalUniversitario Gregorio Maranon, Gastroenterology, Madrid,Spain, 5Hospital Universitari Vall d’Hebron, Unitat AtencioCrohn-Colitis, Barcelona, Spain

Background: Randomized controlled trials (RCTs) provide thebest scientific evidence for the efficacy of biological drugin the treatment of inflammatory bowel disease (IBD) inselected conditions. In contrast, observational studies providethe biological drug effectiveness in real clinical practice (CP).We aimed to compare the theoretical efficiency of biologicaldrugs (RCTs conditions) in IBD patients with their effectivenessin PC and to assess factors impacting this discrepancy.Methods: We performed a retrospective multicenter cohortstudy of adult patients with Crohn’s disease (CD) and ulcerativecolitis (UC) treated with anti-TNF agents and followed-up forat least 1 year, randomly selected from five Spanish tertiarycenters (EFIFECT cohort). Patients who met the RTCs selectioncriteria were included for the analysis. Outcomes of biologicaltherapy in CP were compared with those hypotheticallyobtained if the patient would be included in RCTs.Results: One hundred seventy-one patients of 378 (130 CDand 41CU) were included. The overall clinical benefit at oneyear was higher in CP than hypothetical RCTs (68.4% vs.44.4%, p < 0.001). The percentages of clinical remission andresponse in CD patients were 50.8% and 19.2% in the CP,