be drug specific in some patients, rather than class specific and alternative anti-TNF agentsmay not produce this reaction.

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Overall Incidence of Hepatosplenic T Cell Lymphoma in Patients WithInflammatory Bowel Disease on Thiopurines: A Meta-Analysis of ThreePopulation Based StudiesDavid Kotlyar, Javier P. Gisbert, James D. Lewis, Colleen M. Brensinger, LaurentBeaugerie, Wojciech Blonski, Robert Hirten, Maria Chaparro, Manuel Van Domselaar,Gary R. Lichtenstein

Background: Hepatosplenic T-cell lymphoma is a feared complication of thiopurine treatmentfor Inflammatory Bowel Disease. While estimates of the risk of Hepatosplenic T-celllymphoma have been stated in the past, it has not been possible to calculate an estimatedincidence as no population based studies of patients with IBD on thiopurines has yet reporteda case of HSTCL. Aims: Here we aim to calculate the incidence of HSTCL via a meta-analysisof three population based studies of IBD patients taking thiopurine therapy. We also aimto calculate the relative risk of HSTCL. Methods: We included three population based studiesin our analysis, a study from the UK, (Armstrong 2010 Am J of Gastro), one from France(CESAME; Beaugerie 2009 Lancet), and one from Spain (Gisbert Gastro 2010). In our studydata were extracted from the Spanish collaborative registry ENEIDA (of which the Gisbertstudy was published). We examined overall incidence, the incidence in men, those less than36 years old, and men under 36 years old. 95% confidence intervals (CIs) were estimatedby summing observed and expected cases of lymphoma. CIs assumed a Poisson distribution.To examine for heterogeneity, the deviance statistic from Poisson regression models wasexamined. All patient studies were in compliance with the Helsinki Protocol. Results: Onecase of HSTCL was present among the three studies, (in ENEIDA). The overall incidencewas 1.32 cases per 100,000 person-years with a number needed to harm (NNH) of 1:75,488patients per year. For men, the incidence was 2.69 cases per 100,000 person-years with anNNH of 1:37,208 per year, and in those under 36 years of age the incidence was 3.63 casesper 100,000 person years with an NNH of 1:27,528. In men under 36, the incidence was7.93 cases per 100,000 person years with an NNH of 1:12,616 patients per year. Confidenceintervals were very large secondary to only one patient being described and there was nosignificant heterogeneity (see Table 1). Conclusion: In a recent systematic review of HSTCLin IBD (Kotlyar 2010, Clin Gastroenterol Hepatol), while incidence could not be estimated,the absolute risk was estimated at being 1:44,444 overall and 1:7404 in men under 35.These estimates accord with calculated numbers needed to harm of 1:75,488 per year overalland 1:12,616 per year in men under 36.Confidence Interval for Incidence and Tests for Heterogeneity

Test for heterogeneity among 3 studies: χ2 = 3.59, 2df, p-value = 0.1657Studies Comprising Meta-Analysis

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Non-Organ Specific Autoantibodies (NOSA) Induced by Anti-Tumor NecrosisFactor-Alpha Agents for Inflammatory Bowel Disease (IBD) Are NotAssociated With Overt Autoimmune DiseaseMaria Cappello, Ivana Bravatà, Claudia Randazzo, Anna Licata, Piero Almasio, AntonioCraxì

Aim. Anti-tumor necrosis factor-alpha agents have a good safety profile but they occasionallymay induce adverse effects, including de novo production of non-organ specific autoantibod-ies (NOSA) and occurrence of lupus-like syndrome. However the clinical relevance of NOSAis still unclear. We evaluated the prevalence of NOSA and autoimmune manifestations amonginflammatory bowel disease (IBD) patients treated with anti-TNFα agents. Materials andMethods. IBD patients on anti-TNF-α therapy were tested for NOSA production beforetreatment and after 24 and 54 weeks. Sera were analyzed for NOSA against nuclear antigens(ANA), smooth muscle (SMA), mitochondria (AMA), liver-kidney microsomes (LKM) anddouble stranded (ds) DNA by indirect immunofluorescence. Data regarding demographicand clinical features, anti-TNFα treatment, concomitant immunosuppressive medication,development of autoimmune manifestations (arthralgia, lupus-like syndrome, vasculitis, skinrashes, autoimmune hepatitis) were recorded. Results. We studied forty patients (16 males,median age 46 yrs, range 21-69), 32 with Crohn's disease (CD) and 8 with ulcerative colitis(UC). Eighteen (45.0%) were treated with infliximab, 4 (10.0%) with adalimumab and18 (45.0%) with infliximab followed by adalimumab. 26 patients received concomitantimmunosuppressive medication (9 azathioprine and 17 steroids). Overall ANA positivitywas observed in 22 (55.0%) subjects (16/32 in CD and 6/8 with UC, P ns), SMA positivityin 5 (12.5%) and only one AMA positivity. Among ANA positive patients, 2 showed anti-dsDNA positive autoantibodies. ANA positivity was detected in 13 out of 18 (72.2%) patientstreated with infliximab, 9 out of 18 (50.0%) with infliximab plus adalimumab and in nonein 4 patients treated with adalimumab alone (P = 0.027). Concomitant immunosuppressivetherapy had no influence on ANA positivity development. None of these patients experiencedlupus-like syndrome. Four subjects developed peripheral poliarticular arthralgia involving

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mainly small joints after a mean period of 6.0 ± 11.2 months. Biological therapy was notwithdrawn, except in a single UC patient with ANA and AMA positivity who developedalso a skin rash. Conclusions. NOSA are produced in high proportion of IBD patients onanti-TNF-alpha therapy and appear more frequently in infliximab-treated patients. They arerarely associated with clinical features of autoimmunity and in most cases do not requirediscontinuation of therapy.

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Flu and Pneumoccocal Vaccination in IBD Immunosuppressed PatientsJennifer S. Au, Aarati Malliah, Albert G. Crawford, Bettina Berman, Valerie Pracilio, NeilGoldfarb, Patricia L. Kozuch

Purpose: Despite recommendations that immunosuppressed IBD patients be vaccinatedagainst Influenza (flu) and S. pneumoniae (pneumococcus), low vaccination rates in thispopulation are reported. The purpose of this study was to determine baseline and post-intervention rates of flu and pneumococcal vaccination in immunosuppressed IBD patientsat our institution. Methods: 99 IBD outpatients taking ≥1 immunosuppressant completeda survey regarding 2008-09 flu and past pneumococcal vaccination; they could mark oneor more reasons for vaccination or non-vaccination. Additionally, chart review was conductedto assess documentation of these vaccinations. Interventions including health-care providereducation, reminder emails to physicians and placement of a vaccine documentation formin the chart were implemented prior to the 2009-10 flu season. The same survey was thenadministered to second group of 99 immunosuppressed IBD patients and a subsequent chartreview was completed. Results: A total of 159 patients participated in the two-part study:99 completed surveys at each time point with 39 repeat participants. There was no significantdifference in flu or pneumococcal vaccine pre and post intervention (flu: 66% vs. 65%;pneumococcal: 38% vs. 45%). There was no statistically significant difference in vaccinationrates among the subset of patients surveyed at both time points although a 10% increasein pneumococcal vaccination was noted post-intervention. Documentation rates of flu (22%vs. 26%) and pneumoccocal (30% vs. 31%) vaccines did not change. Significantly morewomen than men received a flu vaccine pre-intervention and a pneumovax post-intervention.The most common reason cited for receiving both vaccines, before and after intervention,was GI doctor recommendation. More subjects who were vaccinated for flu cited IBD as areason after the intervention as compared to before, and more subjects in the post comparedto pre-intervention group who were not vaccinated for flu acknowledged that their GIdoctors had recommended vaccination. On the other hand, more subjects in the post-intervention group were unaware flu vaccination was necessary. While the most commonreason for not receiving a pneumovax remained “not being told I needed one” the percentagedecreased non-significantly post-intervention. Conclusion: While baseline flu and pneumoc-occal vaccination rates among immunosuppressed IBD patients exceeded previously reporteddata, approximately one-third and two-thirds of patients respectively did not receive thesevaccinations. Provider education and reminder tools did not increase patient vaccinationrates and chart documentation remained poor. However, GI doctor recommendation wasthe most commonly given reason for vaccination. Future research may emphasize patientrather than provider education and reminders.

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Assessment of the Safety and Efficacy of Biologic Monotherapy VersusCombination Biologic and Immunosuppressant Therapy for the Treatment ofInflammatory Bowel DiseaseChelle Wheat, Stacey Lynema, Cynthia W. Ko, Scott Etter, Cory Cullinan, Mika N.Sinanan, Scott D. Lee

Infliximab, adalimumab, certolizumab pegol, and natalizumab are biologic medicationsfrequently and successfully used for the treatment of Inflammatory Bowel Disease (IBD),including Crohn's Disease (CD) and Ulcerative colitis (UC). With biologic therapies thereis the risk of development of antibodies which can result in loss of response as well as allergicreaction. Using immunosuppresants in conjunction with biologic therapy can decrease therisk of development of these antibodies and the resultant loss of response, as well as otheradverse effects. In addition, combination therapy has been shown to be more effective thaneither immunosuppresants or biologics alone. There is limited data on the long term safetyof this combination of therapy regarding any increases in the risk for infection, neoplasms,and other adverse events. The aim of this study was to investigate whether there is a differencein the incidence of the number of infections, neoplasms, and adverse effects between patientsbeing treated with biologic monotherapy and patients being treated with dual immunosup-pressant therapy. Methods: Following receipt of IRB approval, 950 total eligible patients,who had received either biologic monotherapy or biologic therapy in combination withimmunosuppression, were identified from the University ofWashington IBD Clinic's databaseand included in the dataset for analysis. Each individual infection that required treatmentwith antibiotics, antiviral or antifungal therapy; patient reported and physician assessedadverse effects; as well as any neoplasms were captured along with the correspondingbiological therapy category. Logistic regression was utilized in order to assess the risk ofinfection with respect to therapy group and was stratified by the individual biologic used.These outputs were reported in the form of odds ratios (ORs) with the associated 95%confidence intervals (CIs). Results: In this cohort, there was no significant difference in riskof infection for combination immunosuppressive therapy compared to biologic monotherapy(adjusted OR 1.01, 95% CI .429-2.37). Dual therapy was not associated with an increasedrisk of adverse effect (adjusted OR .659, 95% CI .321-1.35) nor an increase in risk forneoplasm . None of the individual biologics correlated with any change in risk in regardsto adverse event or neoplasm. Conclusions: Given the evidence showing increased efficacyand a decrease in antibody formation with combination therapy, it is critically importantto understand if there is an increase in infectious or other complications. These results showthat in a large cohort, there is no increased risk of infection, other adverse effects orneoplasms. This evidence suggests that concerns of infections or neoplasms are not reasonsto avoid combination therapy in patients with IBD.

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