What is the evidence to repeat a negative QuantiFERON (Quantiferon-Gold) test when switching a patient from one biological agent to another?

From the Guidelines

There is limited evidence to support repeating a negative QuantiFERON-Gold test when switching a patient from one biological agent to another, and it is generally not recommended unless new risk factors for tuberculosis exposure have developed. The primary concern with biological agents, particularly TNF inhibitors like adalimumab, infliximab, and etanercept, is the risk of reactivating latent tuberculosis infection (LTBI) 1. Once a patient has been screened and found negative for LTBI before their first biologic, the risk profile doesn't significantly change when switching to another biologic, assuming no new TB exposures. However, if the patient has traveled to TB-endemic regions, had known TB exposure, or developed new risk factors since the initial test, repeating the QuantiFERON-Gold would be prudent.

Key Considerations

• The risk of reactivating LTBI is established before initiating any biologic therapy rather than being specific to switching between agents 1.
• Patients who test positive for TST or IGRA at baseline often remain positive for these tests even after successful treatment of TB, and repeating tests will not help in diagnosis of recurrent TB 1.
• Yearly testing for latent TB should be done in patients at high risk, and screening should be done at the discretion of the dermatologist for patients who are not at high risk 1.

Clinical Judgment

Some clinicians may opt to repeat testing as a precautionary measure if the switch to a new biologic occurs several years after the initial screening, though this is based more on clinical judgment than strong evidence. The rationale is that biological agents, particularly those targeting immune pathways, can potentially increase susceptibility to TB infection or reactivation.

Recommendations

• Repeating a negative QuantiFERON-Gold test is not routinely recommended when switching a patient from one biological agent to another, unless new risk factors for tuberculosis exposure have developed 1.
• Clinicians should consider the patient's individual risk factors and medical history when deciding whether to repeat testing.
• Annual testing for latent TB should be considered for patients at high risk, and screening should be done at the discretion of the dermatologist for patients who are not at high risk.

From the Research

Evidence for Repeating a Negative QuantiFERON Test

When switching a patient from one biological agent to another, the decision to repeat a negative QuantiFERON test is based on several factors, including the risk of tuberculosis reactivation and the potential for false-negative results. The following points summarize the evidence:

• Test Reproducibility: Studies have shown that the QuantiFERON test has substantial concordance when repeated, with a kappa value of 0.72 2. However, the test results can be affected by various factors, including immunosuppressive therapy and biological agents.
• Risk of Tuberculosis Reactivation: The risk of tuberculosis reactivation in patients with negative QuantiFERON test results is low, with one study reporting a rate of 0.3% 2.
• Indeterminate Results: Indeterminate results can occur, especially in elderly and immunocompromised patients, and are often due to positive control failure 3.
• Weakly Positive Results: Weakly positive results can be confusing, and repeated testing may yield negative results in up to 69% of cases 4.
• Cumulative False-Positive Results: Cumulative false-positive results can occur when the QuantiFERON test is repeated annually, with up to 27.4% of individuals having a positive result after 7 years 5.
• Reversion of QuantiFERON Test: Reversion from positive to negative results can occur, especially in healthcare workers with lower baseline QuantiFERON test results 6.

Factors to Consider

When deciding whether to repeat a negative QuantiFERON test, the following factors should be considered:

• Patient Risk Factors: Patients with risk factors for tuberculosis, such as immunosuppressive therapy or biological agents, may require more frequent testing.
• Test Results: Weakly positive or indeterminate results may require repeated testing to confirm the diagnosis.
• Clinical Judgment: Clinical judgment should be used to determine the need for repeated testing, taking into account the patient's individual risk factors and medical history.

Summary of Evidence

The evidence suggests that repeating a negative QuantiFERON test may not be necessary in all cases, especially if the patient has no risk factors for tuberculosis and the initial test result was negative. However, clinical judgment should be used to determine the need for repeated testing, and factors such as test reproducibility, risk of tuberculosis reactivation, and patient risk factors should be considered. 2, 3, 4, 5, 6