Gut reaction

Tb Testing in IBD Patients - QuantiFeron vs. PPD

Jason Swoger, MD, Gastroenterology, 08:21PM Jun 1, 2010

The reactivation of infections due to encapsulated organisms, such as tuberculosis, has long been recognized as a potential risk of anti-TNF therapy.  Pre-treatment testing for Tb has long been recommended,  but studies are beginning to evaluate the best methods of testing.

A 2008 study published in the AJG by Schoepfer et al. reported a trial of the interferon-gamma release assay (Quantiferon) vs. Tuberculin skin test (TST) for screening patients with IBD.  The sensitivity of the TST was thought to be low in patients on immunosuppressive therapy, leading to false negative tests.  In addition, false positive tests, secondary to a history of BCG vaccination, or infection with non-tuberculous mycobacterium, could potentially decrease the specificity of the TST.  The Quantiferon test uses an enzyme-linked immunosorbent assay to measure antigen-specific production of interferon-gamma by T cells in blood exposed to M. Tuberculous antigens.  This was thought to increase both the specificity and sensitivity of the test, in comparison to the TST.  The genes encoding the antigens used in the assay are not present in the BCG vaccine or in non-tuberculous mycobacterium.  Cost and laboratory equipment are disadvantages of this assay, while an advantage is that it can be completed in one patient visit.

This study reported on 168 IBD patients and 44 controls (health-care workers, at higher risk of Tb exposure).  81% of IBD patients were on concomitant immunosuppressive therapy.  A positive quantiferon was found in 8.3% of IBD patients, compared to a positive TST in 18% of IBD patients.  The values among controls were 9% and 43%, respectively.  71% of study participants had received the BCG vaccine, which did not influence positive quantiferon results.  There was a negative correlation between the quantiferon assay and the TST in IBD patients, with a kappa value of -0.0297 (when BCG status not considered).  Kappa values were better in the non-IBD group (0.1302), and the agreement between the tests was significantly higher in controls vs. IBD patients (p=0.044).

Among immunosuppressed IBD patients, there were significantly lower rates of positive TST compared to non-immunosuppressed IBD patients, while quantiferon results were not influenced by the use of immunosuppressant medications.  In summary, there was less concordance between tests in the IBD patients compared to controls, quantiferon results seemed to be influenced less by prior BCG vaccination, and the quantiferon assay may be less affected by immunosuppression.

At the recent DDW, 2 abstracts added to the data regarding Tb testing in IBD patients.  Guidi et al. reported their experience with 101 Italian IBD patients.  55.4% were on immunosuppressive therapy.  4 patients had positive findings on both tests, 2 patients had positive quantiferon with negative TST (one on budesonide and one on AZA), and 1 previously vaccinated patient had a positive TST and a negative quantiferon.  They found a significant overall concordance between tests (p<0.0001), though this was a population at low risk for Tb, and with a low rate of BCG vaccination (only 1 patient).  The authors suggest combining the testing methods, especially in immunosuppressed patients, but there seemed to be general agreement overall.

However, Belard et al. evaluated the effect of corticosteroids in 265 patients with autoimmune diseases.  Patients underwent CXR, TST, and quantiferon.  There was a lower quantiferon response in patients on corticosteroids, or on other treatments.  Again, there was poor concordance between the 3 testing methods.  Kappa values for TST/quantiferon were 0.05, for TST/CXR were 0.145, and for quantiferon/CXR were -0.04.  The authors cautioned against the risk of false negative testing in patients on corticosteroids.

The quantiferon assay is not universally available, and a comprehensive cost/benefit analysis has not been carried out in the IBD population.  The data reviewed above does seem to show less false positive tests, due to BCG vaccination, with the quantiferon assay.  Data on testing results on immunosuppressive therapy are mixed, though the quantiferon assay may be superior to TST.  The level of Tb risk - due to prior vaccination, work exposure, or coming from a high-risk country - may play a role in individualizing our evaluation of Tb risk prior to anti-TNF use.  At our institution, we are beginning to test for Tb early on in the disease course, or immediately upon hospitalization, in order to attempt to diminish the influence of immunosuppressive therapy on the results.  Hopefully, as the Quantiferon test becomes more widely available, we may be able to better tailor testing recommendations based on individual patient risk factors, in order to optimize our cost/benefit ratios.

If others are using one or the other of these tests, or have experience to share in IBD patients, either receiving or not receiving immunosuppressants, we would like to hear your experience with these tesing methods.

--------

Jason Swoger
Jason Swoger, MD, MPH, is Assistant professor of Gastroenterology at University of Pittsburgh Medical Center (UPMC). Dr. Swoger completed his internal medicine residency at the Cleveland Clinic, and then went on to complete a fellowship in gastroenterology at Mayo Clinic, in Rochester, Minnesota. As a fellow, Dr. Swoger began to focus on inflammatory bowel disease and completed several clinical research projects aimed at the treatment of both ulcerative colitis and Crohn's disease. Dr. Swoger joined the faculty at UPMC in August 2009 and is seeing patients and conducting clinical research and clinical trials as part of the UPMC Inflammatory Bowel Disease Center.

Link