What is the recommended management for a patient on Adalimumab (adalimumab) with a positive Quantiferon (Quantiferon-Gold) test?

Management of Patients on Adalimumab with Positive Quantiferon Test

Patients on adalimumab with a positive Quantiferon-Gold test should receive prophylactic treatment for latent tuberculosis infection (LTBI) with isoniazid, ideally initiated at least one month before starting adalimumab or immediately upon detection if already on therapy.

Background and Risk Assessment

Adalimumab, as a TNF-α inhibitor, significantly increases the risk of tuberculosis reactivation. This occurs because TNF-α plays a crucial role in granuloma formation and maintenance, which contains latent TB infection. When this cytokine is blocked, previously contained TB can reactivate, often presenting as disseminated disease rather than typical pulmonary TB.

Diagnostic Considerations

• A positive Quantiferon-Gold test in a patient on adalimumab indicates latent TB infection that requires immediate attention
• False-negative results can occur in immunosuppressed patients, particularly those on concurrent immunosuppressive medications 1
• The sensitivity of Quantiferon-Gold may be affected by anti-TNF therapy itself, potentially causing false-negative results 1

Management Algorithm

For Patients Starting Adalimumab:

1. Pre-treatment screening:

   • Quantiferon-Gold or T-Spot TB test (preferred over tuberculin skin test in immunosuppressed patients) 1
   • Chest radiograph to rule out active TB 1
   • Risk factor assessment for TB exposure

2. If Quantiferon is positive:

   • Rule out active TB with chest radiograph and symptom assessment
   • Initiate LTBI prophylaxis (typically isoniazid) at least 1 month before starting adalimumab 1
   • Complete the full course of LTBI treatment

3. If Quantiferon is negative:

   • Proceed with adalimumab therapy
   • Annual TB screening for high-risk patients 1

For Patients Already on Adalimumab with Newly Positive Quantiferon:

1. Rule out active TB:

   • Chest radiograph
   • Symptom assessment (fever, night sweats, weight loss, cough)
   • Consider additional testing if symptoms present

2. Initiate LTBI treatment immediately:

   • Isoniazid prophylaxis is the standard approach
   • Consider consultation with infectious disease specialist 1

3. Decision regarding adalimumab:

   • If no signs of active TB: adalimumab can generally be continued while on LTBI treatment
   • If active TB is suspected: temporarily discontinue adalimumab until TB treatment is established and infection is controlled

LTBI Treatment Regimens

• First-line: Isoniazid for 9 months
• Alternative regimens:
  • Rifampin for 4 months
  • Isoniazid plus rifapentine weekly for 3 months (directly observed therapy)

Monitoring During Treatment

• Monitor for hepatotoxicity with liver function tests
• Assess for peripheral neuropathy in patients on isoniazid
• Continue annual TB screening while on adalimumab 1

Special Considerations

• Patients with prior TB treatment still require LTBI treatment if exposed to active TB 1
• Patients from TB-endemic regions may require more intensive screening and monitoring
• Quantiferon-Gold may remain positive after successful treatment of LTBI; clinical judgment is needed for interpretation of subsequent positive tests 1

Pitfalls to Avoid

1. Delaying LTBI treatment: Reactivation risk is highest in the first months of anti-TNF therapy 2
2. Inadequate screening: Relying solely on tuberculin skin test in immunosuppressed patients may miss LTBI due to anergy 3
3. Failure to complete LTBI treatment: Incomplete treatment may not prevent TB reactivation
4. Overlooking atypical presentations: TB in patients on adalimumab often presents as extrapulmonary or disseminated disease 2
5. Neglecting annual screening: Continued monitoring is essential as new TB exposure can occur at any time 1

The combination of both Quantiferon-Gold and tuberculin skin test may provide higher sensitivity for LTBI detection in patients receiving adalimumab 4, especially in regions with high TB prevalence.