What precautions are needed for patients with Hepatitis B (HBV) before starting Tofacitinib (Xeljanz) therapy?

Hepatitis B Screening and Management Before Starting Tofacitinib Therapy

All patients should be screened for hepatitis B virus (HBV) infection before starting tofacitinib, and appropriate antiviral prophylaxis must be initiated for HBsAg-positive patients to prevent potentially fatal HBV reactivation. 1

Screening Requirements

Before initiating tofacitinib therapy, comprehensive HBV screening should include:

• Hepatitis B surface antigen (HBsAg)
• Hepatitis B core antibody (anti-HBc total or IgG)
• Hepatitis B surface antibody (anti-HBs)

This complete screening panel is essential to identify both active and past HBV infection, as both scenarios carry risks of reactivation during immunosuppressive therapy 1, 2.

Risk Assessment and Management Algorithm

For HBsAg-positive patients (chronic HBV infection):

1. Mandatory antiviral prophylaxis with high barrier to resistance agents:

   • Entecavir (0.5 mg daily)
   • Tenofovir disoproxil fumarate (300 mg daily)
   • Tenofovir alafenamide (25 mg daily) 1, 3

2. Timing of prophylaxis:

   • Start antiviral therapy before or at the latest simultaneously with tofacitinib
   • Continue for at least 6 months after discontinuation of tofacitinib 1

3. Monitoring during treatment:

   • HBV DNA levels every 3 months
   • Liver function tests (ALT/AST) monthly until normalized, then every 3 months 3
   • Coordinate care with a hepatologist 1

For HBsAg-negative/anti-HBc-positive patients (past HBV infection):

1. Monitoring approach:

   • Regular monitoring of HBsAg, ALT, and HBV DNA every 3 months during therapy and up to 6 months after 1
   • Initiate antiviral therapy immediately if HBV reactivation occurs (HBsAg reappearance or HBV DNA detection) 1

2. Consider prophylaxis in high-risk scenarios:

   • Concomitant use of other immunosuppressants (especially corticosteroids)
   • History of elevated HBV DNA levels
   • Evidence of liver cirrhosis 1

Evidence for HBV Reactivation Risk with Tofacitinib

Tofacitinib poses a significant risk for HBV reactivation. A study of RA patients receiving tofacitinib found:

• 33.3% reactivation rate in HBsAg-positive patients without antiviral prophylaxis
• 3.1% reactivation rate in HBsAg-negative/anti-HBc-positive patients
• Incidence rate of 250 per 1000 person-years in HBsAg-positive patients without prophylaxis 4

This demonstrates that tofacitinib carries a moderate risk of HBV reactivation, particularly in HBsAg-positive patients, but antiviral prophylaxis is highly effective in preventing reactivation 4.

Common Pitfalls to Avoid

1. Incomplete screening: Only 24-29% of patients receive complete HBV screening before starting tofacitinib, leaving many at risk 2. Always perform the full 3-test panel.

2. Using lamivudine for prophylaxis: Avoid lamivudine due to high resistance rates. Use high-barrier agents (entecavir, tenofovir) instead 1.

3. Premature discontinuation of prophylaxis: Continue antiviral therapy for at least 6 months after stopping tofacitinib to prevent delayed reactivation 1.

4. Failure to monitor: Regular monitoring of HBV DNA and liver enzymes is essential, even with prophylaxis 3.

5. Overlooking HBsAg-negative/anti-HBc-positive patients: While lower risk than HBsAg-positive patients, they still require monitoring as reactivation can occur 4.

By following these guidelines, clinicians can effectively minimize the risk of HBV reactivation and its potentially severe consequences in patients receiving tofacitinib therapy.