What to do with a patient with a positive TB (Tuberculosis) Quantiferon test and ankylosing spondylitis, planned to start Humira (Adalimumab), with no respiratory symptoms and a normal chest X-ray?

Management of Latent Tuberculosis Infection Before Starting Adalimumab in Ankylosing Spondylitis

The patient with positive TB QuantiFERON test and ankylosing spondylitis must receive treatment for latent tuberculosis infection (LTBI) for at least 1 month before starting adalimumab therapy.

Assessment of Latent TB Infection

The patient presents with:

• Positive TB QuantiFERON test
• Diagnosis of ankylosing spondylitis
• Plan to start adalimumab (Humira)
• No respiratory symptoms
• Normal chest X-ray

This clinical picture is consistent with latent tuberculosis infection (LTBI) rather than active TB disease. The absence of respiratory symptoms and normal chest X-ray help rule out active TB, but treatment for LTBI is still mandatory before starting adalimumab.

Rationale for LTBI Treatment

Adalimumab carries a significant risk for TB reactivation due to its TNF-α inhibitory effects:

• The FDA black box warning for Humira explicitly states: "Perform test for latent TB; if positive, start treatment for TB prior to starting HUMIRA" 1
• TNF-α plays a critical role in granuloma formation and maintenance, which contains dormant TB bacilli
• Patients with ankylosing spondylitis on TNF inhibitors have increased risk of TB reactivation

Treatment Protocol

1. Initiate LTBI treatment immediately:

   • First-line regimen: Isoniazid 300 mg daily for 9 months with pyridoxine (vitamin B6) supplementation 2
   • Alternative regimen: Rifampin 600 mg daily for 4 months (if isoniazid intolerance is a concern)

2. Timing of adalimumab initiation:

   • Delay adalimumab for at least 1 month after starting LTBI treatment 2
   • This allows time for the anti-TB medication to effectively reduce the bacterial load

3. Monitoring during treatment:

   • Monthly clinical assessment for:
     • Medication adherence
     • Signs of hepatotoxicity (nausea, vomiting, abdominal pain, jaundice)
     • Peripheral neuropathy (with isoniazid)
   • Baseline liver function tests (LFTs) before starting treatment
   • Regular LFT monitoring, especially in patients >35 years, with history of liver disease, or taking other hepatotoxic medications

Follow-up After Starting Adalimumab

• Continue to monitor for signs and symptoms of TB reactivation during adalimumab therapy
• Annual TB screening is recommended for patients on long-term adalimumab therapy
• Maintain clinical vigilance for TB symptoms for at least 6 months after discontinuation of adalimumab

Important Considerations

• Do not start adalimumab without LTBI treatment: The risk of TB reactivation is highest within the first 3 months of TNF inhibitor therapy 3
• Complete the full course of LTBI treatment: Even after starting adalimumab, the full LTBI treatment course must be completed
• Consultation: Collaboration between rheumatology and infectious disease/TB specialists is strongly recommended for optimal management

Potential Pitfalls

1. Delaying LTBI treatment: This increases the risk of TB reactivation once adalimumab is started
2. Starting adalimumab too soon: Beginning adalimumab before adequate TB treatment increases reactivation risk
3. Inadequate monitoring: Failing to monitor for hepatotoxicity during isoniazid treatment
4. Incomplete treatment: Not completing the full course of LTBI therapy

By following this protocol, you can safely manage the patient's ankylosing spondylitis with adalimumab while minimizing the risk of TB reactivation.