What is the incidence of false negative tuberculosis (TB) results in patients taking Rinvoq (upadacitinib)?

Incidence of False Negative TB Results When Using Rinvoq (Upadacitinib)

Patients taking Rinvoq (upadacitinib) have an increased risk of false negative tuberculosis test results due to JAK inhibitor-induced immunosuppression, which can affect both tuberculin skin tests (TST) and interferon-gamma release assays (IGRAs). While the exact incidence of false negative results specifically with Rinvoq is not precisely quantified in current literature, understanding this risk is critical for proper TB screening in these patients.

Mechanism of False Negative TB Results with Rinvoq

JAK inhibitors like upadacitinib can cause immunosuppression that affects TB testing in several ways:

• Interferes with T-cell function required for proper immune response in TB testing
• Reduces interferon-gamma production needed for positive IGRA results
• Diminishes delayed-type hypersensitivity response required for TST reactivity

TB Testing Considerations with Rinvoq

Pre-Treatment Screening

• TB screening should be performed before starting Rinvoq therapy 1
• Ideally, screening should occur before any immunosuppression to minimize false negative results 1
• Combination of clinical risk assessment, chest X-ray, and either TST or IGRA (or both) is recommended 1

Testing Accuracy

• Both TST and IGRA results are negatively affected by immunosuppressive therapy 1
• The PPD skin test has a reported false-negative rate of 25% during initial evaluation of persons with active tuberculosis, which may be higher in immunosuppressed patients 1
• Immunosuppression can cause either specific (early in disease) or nonspecific (due to medications like JAK inhibitors) false negative results 1

Risk of TB Reactivation with Rinvoq

• JAK inhibitors like upadacitinib increase the risk of TB reactivation 1
• A study of tofacitinib (another JAK inhibitor) found TB to be the most common opportunistic infection, with more severe and extrapulmonary forms than in the general population 1

Recommendations for TB Testing in Rinvoq Patients

1. Initial Testing Strategy:

   • Use combination of risk stratification, chest X-ray, and preferably IGRA testing before starting Rinvoq 1
   • Consider using both TST and IGRA in high-risk patients to maximize sensitivity 1

2. During Treatment:

   • Consider re-screening during JAK inhibitor therapy, especially for patients with higher TB risk (living in or traveling to high TB incidence areas) 1
   • Annual re-screening may be appropriate for patients on long-term therapy 1

3. Test Interpretation:

   • A positive result on either test should be considered evidence of TB infection in immunosuppressed patients 2
   • Indeterminate results may occur in up to 12% of IGRAs in immunosuppressed patients 2
   • For patients with negative initial tests but high clinical suspicion, consider repeat testing after 8-10 weeks 3

Pitfalls and Caveats

• False negative TB test results are more common in patients taking immunosuppressive medications like Rinvoq 1
• Relying solely on negative TB test results in immunosuppressed patients may lead to missed LTBI diagnoses
• The Centers for Disease Control and Prevention notes that because of the low sensitivity of TB tests in immunosuppressed patients, they cannot be used to eliminate the possibility of active tuberculosis 1
• Patients with consistently high interferon-gamma levels on initial positive IGRA may not need serial testing due to high consistency in results 4

In conclusion, while specific data on false negative rates with Rinvoq is limited, clinicians should assume an increased risk of false negative TB test results in these patients and implement comprehensive screening strategies before initiating therapy and consider periodic re-screening during treatment.