What is the recommended treatment for latent tuberculosis (TB) infection in a patient with a positive Montoux (Mantoux) test and TB Gold test prior to initiating tofacitinib (Xeljanz)?

Treatment of Latent Tuberculosis Before Starting Tofacitinib

Patients with positive Mantoux test and TB Gold test should complete at least one month of latent tuberculosis treatment prior to starting tofacitinib therapy to prevent TB reactivation.

Diagnosis Confirmation

• Positive Mantoux test and TB Gold test strongly indicate latent tuberculosis infection (LTBI)
• Before starting treatment, active TB must be excluded through:
  • Chest radiography to rule out pulmonary TB
  • Clinical evaluation for symptoms of active TB (cough, fever, night sweats, weight loss)
  • If any suspicion of active TB, obtain respiratory samples (sputum) for acid-fast bacilli smear and culture 1

Treatment Regimens for LTBI

The recommended treatment options for latent TB before starting tofacitinib include:

1. First-line option: Isoniazid for 6 months (6H)

   • Dosage: 5 mg/kg daily (maximum 300 mg daily)
   • Lower risk of hepatotoxicity compared to other regimens
   • Completion rate may be lower due to longer duration 1

2. Alternative option: Rifampin plus isoniazid for 3 months (3RH)

   • Shorter duration may improve adherence
   • Lower risk of developing drug resistance if active TB is present
   • Higher risk of hepatotoxicity compared to isoniazid alone 1

3. Not recommended: Rifampin and pyrazinamide for 2 months (2RZ)

   • Associated with high rates of hepatitis and fatalities
   • Should be avoided 1

Timing of Tofacitinib Initiation

According to the FDA label for tofacitinib (Xeljanz):

• Treatment for latent TB infection should be initiated prior to tofacitinib use 2
• The 2015 American College of Rheumatology guidelines recommend completing at least one month of LTBI treatment before starting tofacitinib 1
• If the inflammatory condition requires urgent treatment, consultation with TB specialists is recommended to balance risks 3

Monitoring During Treatment

• Regular clinical monitoring for:
  • Signs of hepatotoxicity (nausea, vomiting, abdominal pain, jaundice)
  • Symptoms of peripheral neuropathy with isoniazid (consider pyridoxine supplementation)
  • Drug interactions (particularly with rifampin-containing regimens)
• Liver function tests should be monitored periodically, especially in patients with risk factors for hepatotoxicity 3

Special Considerations

• Tofacitinib increases the risk of TB reactivation similar to TNF inhibitors 2, 4
• In a clinical trial of tofacitinib, 263 patients with LTBI were treated with isoniazid concurrently with tofacitinib, and none developed TB, demonstrating the effectiveness of prophylaxis 4
• The incidence of TB in tofacitinib-treated patients varies by regional background TB rates, with higher rates in endemic regions 4

Follow-up After Starting Tofacitinib

• Patients should be monitored for signs and symptoms of TB during and after treatment with tofacitinib
• Periodic evaluation (at intervals <6 months) is recommended to detect symptoms of active TB 3
• Patients who remain at risk for TB exposure should be screened annually 1

Common Pitfalls to Avoid

1. Failing to exclude active TB before starting LTBI treatment
2. Not completing adequate LTBI treatment before initiating tofacitinib
3. Overlooking drug interactions between LTBI treatment and other medications
4. Inadequate monitoring for hepatotoxicity, particularly with isoniazid regimens
5. Assuming that a negative tuberculin test excludes LTBI in immunosuppressed patients

Following these guidelines will help minimize the risk of TB reactivation in patients starting tofacitinib therapy who have evidence of latent tuberculosis infection.