Utility of Quantiferon Gold Assay as a Screening Tool for Latent TB During Active Inflammatory Bowel Disease

Introduction: Tumor necrosis factor alpha (TNFα) is a key cytokine in pathogenesis of Inflammatory Bowel Disease (IBD) and host defense against Tuberculosis (TB). Consequently, TNFα inhibitors result in increased risk of Latent TB (LTB) reactivation. Therefore, screening for LTB is standard protocol prior to initiating anti-TNF therapy.Evidence indicates patients with IBD may display anergy to tuberculin skin testing inthe setting of inflammation resulting in false negative results.The utility of novel LTB screening by Quantiferon Gold assay (QGA) has not been examined in a setting of active IBD. We hypothesize that the QGA may be affected by active inflammation from active Crohn's disease (CD) resulting in equivocal TB screening results. Methods: Patients with CDwho were tested by QGA in the last 5 years were identified. Data extracted for analysis included demographics, CD phenotype, duration of disease, measures of disease activity, imaging and endoscopic data. Statistical analysis was performed using student t-test and chi-square test. Results: We identified 76 patients with CD with QGA testing results. Sixty patients had negative results, 1 was positive and 15 had indeterminate results (Figure 1a). Indeterminate results were more common in younger patients and those previously hospitalized for CD. There was no significant difference between gender, montreal classification, perianal disease, small bowel involvement, smoking status, family history, or extra-intestinal manifestations of IBD (Table 1). In a subset analysis of patients tested during an acute flare (n=29), 13 patients (45%) had an indeterminate test result (Figure 1b). Further analysis showed no correlation between an indeterminate QGA during an acute flare and average ESR or CRP levels (Table 2). However, there was a strong correlation between an indeterminate QGA and active Crohn's flare with ongoing corticosteroid use. Furthermore, indeterminate result was due to inadequate response to positive control in the test (Q-mito-Nil) (table 2).Figure 1Conclusion: Screening for LTB remains standard protocol before initiating anti-TNF therapy. While the QGA is a useful test in this setting, our data suggests that patients with active flare and on steroids at the time of testing may have indeterminate results, which may delay initiation of therapy with anti-TNF agents. An algorithm in patients with indeterminate test result and low risk for TB infection may help minimize delays in initiation of anti-TNF agents.Figure 2Figure 3

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