What is the treatment for latent tuberculosis infection in a patient with a positive TB Quantiferon (Tuberculin Blood Test) test on adalimumab (Humira)?

Treatment of Latent Tuberculosis Infection in a Patient on Adalimumab with Positive TB Quantiferon Test

Patients with a positive TB Quantiferon test on adalimumab should receive treatment for latent tuberculosis infection (LTBI) with either isoniazid for 9 months or rifampin plus isoniazid for 3-4 months before continuing adalimumab therapy. 1, 2

Background and Risk Assessment

Adalimumab (Humira) is a TNF-alpha inhibitor that significantly increases the risk of tuberculosis reactivation. The FDA label for adalimumab explicitly states that patients must be tested for latent TB, and if positive, TB treatment must be started prior to initiating or continuing adalimumab 1. Patients on TNF inhibitors have a 5-fold increased risk of developing TB, which often presents as disseminated disease 3.

Diagnostic Confirmation

Before initiating LTBI treatment:

• Confirm that active TB has been ruled out through:
  • Clinical evaluation for TB symptoms (cough, fever, night sweats, weight loss)
  • Chest radiography to exclude pulmonary TB
  • When indicated, sputum studies or other appropriate specimens for acid-fast bacilli

Treatment Regimens for LTBI

Preferred Regimens:

1. Isoniazid for 9 months 2

   • Dosage: 300 mg daily or 900 mg twice weekly (with directly observed therapy)
   • This is the preferred regimen for patients with HIV infection or radiographic evidence of prior TB

2. Rifampin plus Isoniazid for 3-4 months 2

   • This shorter regimen may improve treatment completion rates
   • Dosage: Rifampin 600 mg + Isoniazid 300 mg daily

3. Rifampin alone for 4 months 2

   • Alternative for patients who cannot tolerate isoniazid or pyrazinamide
   • Dosage: 600 mg daily

Monitoring During Treatment

• Monthly clinical evaluations for all regimens to assess:

  • Medication adherence
  • Signs/symptoms of hepatotoxicity (nausea, vomiting, abdominal pain, jaundice)
  • Other adverse effects

• Baseline laboratory testing indicated for:

  • Patients with HIV infection
  • Pregnant women or those in immediate postpartum period
  • History of chronic liver disease
  • Regular alcohol use
  • Patients on other potentially hepatotoxic medications (like methotrexate) 2

• Monthly liver function tests (LFTs) monitoring recommended when:

  • Abnormal baseline LFTs
  • Chronic liver disease
  • Regular alcohol use
  • Taking other hepatotoxic medications (especially with isoniazid and methotrexate combination) 2

Timing of Adalimumab Therapy

• For patients newly starting adalimumab: Begin LTBI treatment at least 1 month before initiating adalimumab 4
• For patients already on adalimumab: Temporarily discontinue adalimumab until LTBI treatment has been initiated and patient is clinically stable

Special Considerations

• Drug interactions between LTBI treatments and medications commonly used for autoimmune inflammatory rheumatic diseases should be carefully evaluated 2
• Interferon-gamma release assays (IGRAs) like Quantiferon are preferred over tuberculin skin tests (TST) for diagnosing LTBI in patients on immunosuppressive therapy, as they are less affected by glucocorticoids and DMARDs 2
• Regular monitoring for TB symptoms should continue throughout adalimumab therapy, even after completing LTBI treatment, as breakthrough TB can still occur 4

Pitfalls to Avoid

• Do not delay LTBI treatment in patients on adalimumab, as disseminated TB can develop rapidly 3
• Do not rely solely on TST for screening in patients on immunosuppressive therapy, as false negatives are common due to anergy 4
• Do not discontinue LTBI treatment prematurely, as incomplete treatment may not prevent TB reactivation
• Do not ignore indeterminate IGRA results; these warrant careful assessment but should not necessarily preclude TNF inhibitor therapy 5

By following these guidelines, the risk of TB reactivation in patients on adalimumab can be significantly reduced, improving patient outcomes and reducing morbidity and mortality associated with TB disease.