Rifaximin for Preventing Acute Graft Versus Host Disease: Impact on Plasma Markers of Inflammation and T Cell Activation Open Access

Qayed, Muna (2010)

Permanent URL: https://etd.library.emory.edu/concern/etds/z603qx506?locale=en
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Abstract

Abstract
Rifaximin for Preventing Acute Graft Versus Host Disease: Impact on Plasma Markers of
Inflammation and T Cell Activation
By Muna Qayed
Bacterial translocation across damaged gut mucosa is critical in the pathogenesis of acute
graft versus host disease (AGVHD). We conducted a pilot trial to test the hypothesis that
rifaximin would abrogate systemic inflammation and resultant T cell activation in
allogeneic transplant recipients. Twenty adult and pediatric (≥12 years) patients were
enrolled. Rifaximin (400 mg bid) was started on day -10 and continued through day +30.
Plasma samples were collected at baseline, day 0 (pre-transplant) and day 15 to measure
levels of markers of inflammation (soluble TNF receptor 1 [sTNFR1] and interleukin 6
[IL-6]), and donor T cell activation (soluble IL-2 receptor [sIL-2R]). A historical control
group (n=24) was formed from subjects enrolled on a previously conducted study. The
median percentage of rifaximin doses successfully administered was 95%. There were
no serious adverse events attributed to rifaximin. Mean IL-6 concentration decreased by
64% in the treatment group relative to the control group by day 0 (p=0.002). sTNFR1
and sIL-2R did not change in the treatment group relative to the control group. In
multivariate analysis, the odds ratio for developing serious bacterial infection for
rifaximin was 0.44 (95% CI 0.1, 1.9). This pilot study demonstrates that administering
rifaximin to prevent AGVHD is safe and feasible. Rifaximin may limit inflammation as
suggested by its effect on IL-6 levels, but its anti-inflammatory effect may be insufficient
to prevent downstream activation of donor T cells. The role of rifaximin for infection
prophylaxis needs to be investigated in a large scale randomized trial.

Rifaximin for Preventing Acute Graft Versus Host Disease: Impact on Plasma Markers of
Inflammation and T Cell Activation
By
Muna Qayed
MBBS, University of Jordan, 2002
Advisor: Roberd Bostick, MD, MPH
John Horan, MD, MPH
A thesis submitted to the Faculty of the
James T. Laney School of Graduate Studies of Emory University
in partial fulfillment of the requirements for the degree of
Master of Science
in Clinical Research
2010

Table of Contents

Table of Contents


1. Introduction...1

2. Background...3

3. Methods...9

4. Results...17

5. Discussion...21

6. References...25

7. Figures/Tables...28


List of Tables

Table 1...28
Baseline characteristics of study participants and historical controls

Table 2...29
Feasibility of and adherence to rifaximin administration

Table 3...30
Cumulative incidence of clinical GVHD in the treatment and control groups

Table 4...31
Univariate analysis for effects of rifaximin on biomarkers of

inflammation and T cell activation

Table 5...32
Multivariate analysis for effects of rifaximin on biomarkers

of inflammation and T cell activation

Table 6...33
Frequency of types of infections in the treatment and control groups

Table 7...34
Multivariate analysis for bacteremia and serious bacterial infection

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