What tuberculosis (TB) test is recommended prior to initiating biologics?

TB Screening Before Initiating Biologics

Either a tuberculin skin test (TST) or interferon-gamma release assay (IGRA) should be performed in all patients prior to starting biologic therapy, regardless of TB risk factors, with IGRA preferred over TST in patients with prior BCG vaccination. 1

Initial Screening Approach

Universal Screening Requirement

• All patients being considered for biologic therapy must be screened for latent TB infection (LTBI), regardless of whether they have identifiable risk factors for TB exposure. 1
• Take a detailed history to identify CDC-defined TB risk factors including: close TB contacts, foreign birth from high-incidence areas (Africa, Asia, Eastern Europe, Latin America, Russia), frequent/prolonged travel to endemic areas, residence/employment in congregate settings (correctional facilities, long-term care, homeless shelters), healthcare workers serving high-risk populations, and medically underserved/low-income populations. 1

Test Selection Strategy

• Use either TST or IGRA as the initial screening test. 1
• In patients with prior BCG vaccination, IGRA is strongly preferred over TST due to high false-positive rates with TST in this population. 1
• IGRA has higher specificity than TST in BCG-vaccinated individuals because it measures interferon-gamma release to M. tuberculosis-specific antigens not found in BCG vaccines. 2, 3
• In endemic regions with high BCG vaccination rates, IGRA may improve both sensitivity and specificity. 1

Managing Test Results

Positive Initial Test

• Obtain a chest radiograph in all patients with positive TST or IGRA to evaluate for past TB exposure or active TB. 1
• If chest radiograph is positive, obtain sputum for acid-fast bacilli (AFB) smear and culture to rule out active TB. 1
• Consider referral to a TB specialist for further evaluation and treatment planning. 1

Negative Initial Test in High-Risk Scenarios

• A critical pitfall: Patients with rheumatologic diseases may have false-negative TST or IGRA results due to immunosuppression, so a negative test does not definitively exclude LTBI. 1
• In immunosuppressed patients with TB risk factors and negative initial screening, repeat TST or IGRA 1-3 weeks after the initial test. 1
• Even with negative repeat testing, maintain clinical suspicion in patients with significant risk factors. 1

Timing of Biologic Initiation

Latent TB Treatment Protocol

• Biologics can be initiated after completing at least 1 month of latent TB treatment with anti-tubercular medications. 1, 2
• For high-risk patients (close TB contacts, recent immigrants from high-incidence areas, endemic area residents), consider completing the full LTBI treatment course before starting TNF inhibitors. 4
• A 4-month rifampin course is recommended as it is as effective as 9-month isoniazid with superior completion rates and better safety profile. 1, 4

Active TB Management

• Complete the full treatment course for active TB with resolution of symptoms before initiating or resuming biologic therapy. 1
• Consider using non-TNF biologics (IL-17 or IL-12/23 inhibitors) in patients with active TB history, as these carry lower reactivation risk. 1, 4

Ongoing Surveillance

Annual Rescreening Indications

• Perform annual TB screening in patients on biologics who live, travel, or work in situations where TB exposure is likely. 1, 2
• Important caveat: Patients who test positive for TST or IGRA at baseline will typically remain positive even after successful TB treatment, so monitor these patients for clinical signs and symptoms of recurrent TB rather than repeating tests. 1, 2

Additional Screening Considerations

• Screen for hepatitis B virus before starting biologics, as biologics (particularly rituximab) carry risk of HBV reactivation. 2
• Consider screening for HIV and hepatitis C as well in appropriate clinical contexts. 2

Common Pitfalls to Avoid

• Do not skip TB screening in patients without obvious risk factors—universal screening is required regardless of risk profile. 1
• Do not rely solely on TST in BCG-vaccinated patients—this leads to false-positive results and unnecessary LTBI treatment. 1
• Do not assume a negative test excludes LTBI in immunosuppressed patients—consider repeat testing 1-3 weeks later if risk factors are present. 1
• Do not delay appropriate LTBI treatment—biologics should not be started until at least 1 month of anti-tubercular therapy is completed. 1, 2, 4