Tu1309 A Checklist Improves Vaccination, Health Maintenance and Drug Monitoring Adherence in Inflammatory Bowel Disease

AGA Abstracts * Drug monitoring was advised based on manufacturer's guidelines to include appropriate laboratory, CXR, bone density, tuberculosis testing or ophthalmology examinations at product labeling recommended intervals Tu1310 Treatment of Infliximab or Adalimumab Induces Suppression of Circulating CD45ROHigh CD4+ T-Cells in Crohn's Disease Patients After 4 Weeks of Drug Administration Aito Ueno, Rune Wilkens, Humberto Jijon, Mailin Deane, Ronald Chan, John I. Oshiomogho, Ji Li, Gilaad Kaplan, Marietta Iacucci, Paul L. Beck, Remo Panaccione, Stephanie R. Wilson, Kerri L. Novak, Subrata Ghosh INTRODUCTION The prevalence of memory T cells is a rising evidence of chronic inflammation in Crohn's disease (CD)1. The mechanism of action of anti-tumor necrosis factor (TNF) antibody therapies in IBD is multifaceted and involves T cell apoptosis, neutralization of soluble TNF, and down regulation of cell adhesion molecules. We hypothesize that the high prevalence of circulating memory T cells prior to anti-TNF therapy will be reduced by commencing anti-TNF therapy in CD patients. The aim of this study is to assess whether anti-TNF treatment in CD patients can suppress memory T cells, as well as modify immunephenotypes of memory T cells in the circulating compartment. METHODS Blood from consenting CD patients was drawn before (pre-) and/or 4 weeks (4w-) after the initiation of anti-TNF therapy (infliximab or adalimumab). Peripheral blood mononuclear cells (PBMC) were isolated and assessed expression of CD3, CD4, CD45RO, Foxp3, RoRγT, IL-17, IL22, and IFN-γ by flow cytometry. CD4+ T cells were categorized into 3 populations based on CD45RO fluorescent intensity: high (defining as memory cells), low (intermediate), and negative (naïve cells). Expression of intracellular cytokines and transcription factors was investigated in each population to define T cell subsets. Unpaired t-tests were employed to analyze differences between pre- and 4w-TNF therapy groups and RM ANOVA to compare among the CD45RO-based T cell populations. RESULTS Thirteen CD patients were enrolled. Memory (p<0.05) and naïve (p<0.05) cells were significantly decreased (% CD4+ T cells) in the 4w compared to the pre samples and conversely, intermediate population was increased in the 4w compared to the pre group (p<0.05, Fig.1). Expression of Foxp3, RoRγT, and IFN-γ was not significantly different between pre and 4w groups in three CD45RO populations; however, those expressions were population specific in the pre group (Foxp3; high vs. low: p<0.01, high vs. neg: p<0.01: RoRγT; high vs. low: p<0.001, low vs. neg: p<0.05, high vs. neg: p<0.001: and IFN-γ; high vs. low: p<0.01, low vs. neg: p<0.01, high vs. neg: p<0.01) and those differences lost in the 4w group. Expressions of IL-22 and IL-17 were significantly different between memory and intermediate populations in the pre (p<0.05, both) but not in the 4w group. There were no significant differences in CD4+ T cell (% live PBMC) between the 2 time points (p=0.134). CONCLUSIONS Anti-TNF therapy suppressed the frequencies of circulating memory and naïve T cells accompanied by disruptions of the memory, intermediate and naïve T cell subsets such as expressions of Foxp3, RoRγT, and IFN-γ. We speculate that anti-TNF therapy elicits part of its therapeutic effects via the suppression of Memory T cells and modulations of subsets, which contribute to chronicity in CD. REFERENCE 1. Kanai et. al., Curr Opin Gastroenterol 2009;25:306-13

Tu1309 A Checklist Improves Vaccination, Health Maintenance and Drug Monitoring Adherence in Inflammatory Bowel Disease Christopher Knudsen, Catherine S. Manolakis, Jack A. Di Palma Background: Inflammatory bowel disease (IBD) patients are at risk of infection, increased by the use of immunosuppressives and biologics, which also have adverse effects. Advised meticulous monitoring of health maintenance may help avoid these experiences. Methods: Vaccine administration, colorectal dysplasia screening, dermatology, ophthalmology, and gynecologic examinations, bone density testing, tuberculosis and fungus screening, and drug monitoring adherence was reviewed in patients with IBD before and after implementation of an adherence checklist administered at every visit encounter. Results: The study group consisted of 22 females and 17 males with ulcerative colitis (16) or Crohn's Disease (23). There were 28 Caucasians, 9 African Americans, 1 Hispanic, 1 Middle Easterner, and 1 Asian. Average age was 43 years. Prior to implementation of the checklist, appropriate vaccines were ordered in 67% and completed in 58%, and health maintenance evaluations were ordered in 68% and completed in 64%. After implementation of the checklist, vaccines were ordered in 79% and completed in 74%, and health maintenance evaluations ordered in 91% and completed in 78%. Table 1 shows adherence for individual tests and measures. Conclusions: The use of a health maintenance checklist tool for patients with IBD administered at every outpatient encounter enhances health maintenance adherence and should be advocated in routine practice. Additional research is needed to determine if this practice results in improved patient outcomes. Vaccine, health maintenance, and drug monitoring adherence

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AGA Abstracts