What is the management for a patient with a positive Quantiferon (Interferon-Gamma Release Assay) test result who is on adalimumab (adalimumab, a tumor necrosis factor-alpha inhibitor)?

Management of Positive QuantiFERON Test in a Patient on Adalimumab

A patient with a positive QuantiFERON test who is on adalimumab requires immediate initiation of latent tuberculosis infection (LTBI) treatment to prevent tuberculosis reactivation, which is a serious complication of TNF-α inhibitor therapy.

Diagnostic Evaluation

When a patient on adalimumab has a positive QuantiFERON test, the following steps should be taken:

1. Rule out active TB infection:

   • Perform chest radiograph to look for infiltrates, nodules, or cavitary lesions 1, 2
   • Obtain clinical history focusing on TB symptoms (cough >2 weeks, night sweats, weight loss, fever)
   • Physical examination
   • If chest radiograph is abnormal or symptoms are present:
     • Collect 3 sputum specimens (at least 8 hours apart, including one early morning specimen) for:
       • Acid-fast bacilli smear
       • Mycobacterial culture
       • Nucleic acid amplification testing 1

2. Risk assessment:

   • Evaluate prior TB exposure history
   • Assess for additional risk factors (immunosuppression, diabetes, chronic renal failure)
   • Consider country of origin and travel to TB-endemic regions 2

Treatment Protocol

For Positive QuantiFERON without Active TB:

1. Initiate LTBI prophylaxis:

   • Begin isoniazid prophylaxis at least 1 month before starting adalimumab if newly diagnosed 2
   • For patients already on adalimumab:
     • Start isoniazid immediately
     • Consider temporary discontinuation of adalimumab until completion of at least 1 month of LTBI treatment 1, 2

2. LTBI treatment regimens (options):

   • First-line: Isoniazid for 9 months
   • Alternative regimens:
     • Rifampin for 4 months
     • Isoniazid plus rifapentine weekly for 3 months (directly observed therapy) 2

3. Monitoring during LTBI treatment:

   • Monthly clinical assessment for:
     • Adherence to therapy
     • Signs of hepatotoxicity (nausea, vomiting, abdominal pain, jaundice)
     • Peripheral neuropathy (numbness, tingling)
   • Regular liver function tests, especially in patients >35 years, with history of liver disease, or alcohol use 2

For Patients with Active TB:

• Discontinue adalimumab immediately
• Refer to infectious disease specialist
• Initiate full multi-drug TB treatment regimen
• Adalimumab may be restarted after completion of TB treatment or with significant clinical improvement and negative cultures 1

Ongoing Monitoring

1. Annual TB screening:

   • Yearly QuantiFERON-TB Gold testing for patients at high risk (e.g., contact with individuals with active TB, travel to endemic areas) 1, 2
   • Note: QuantiFERON test may remain positive after successful LTBI treatment 1

2. Clinical vigilance:

   • Monitor for TB symptoms at each visit
   • Consider annual chest radiograph at treating physician's discretion 1
   • Remain vigilant for extrapulmonary TB manifestations, including intestinal TB 3

Important Considerations

• TNF-α inhibitors like adalimumab increase TB risk 5-fold, primarily through reactivation of latent TB 4
• TB in patients on adalimumab often presents as disseminated disease rather than typical pulmonary TB 4
• No LTBI prophylaxis regimen is 100% protective; cases of TB reactivation despite LTBI treatment have been reported 3
• Extrapulmonary TB, including intestinal involvement, can occur in patients on adalimumab despite LTBI treatment 3
• Temporary discontinuation of adalimumab may be necessary during febrile illness or active infection, with resumption after resolution 1

By following this structured approach, the risk of TB reactivation in patients on adalimumab with positive QuantiFERON tests can be significantly reduced, improving morbidity and mortality outcomes.