Do I need to check for anti-HBc (antibody to hepatitis B core antigen) total before starting tofacitinib (Janus kinase inhibitor)?

Hepatitis B Screening Before Starting Tofacitinib

Yes, testing for anti-HBc (antibody to hepatitis B core antigen) total is required before starting tofacitinib therapy to prevent potentially life-threatening hepatitis B virus reactivation.

Rationale for HBV Screening Before JAK Inhibitor Therapy

The American Gastroenterological Association (AGA) strongly recommends testing for hepatitis B in all individuals at risk of HBV reactivation prior to immunosuppressive therapy, including JAK inhibitors like tofacitinib 1. This recommendation is based on moderate certainty evidence and is classified as a strong recommendation.

Required Screening Tests:

• Hepatitis B surface antigen (HBsAg)
• Hepatitis B core antibody (anti-HBc) total
• Consider HBV DNA if either HBsAg or anti-HBc is positive

Risk Assessment for HBV Reactivation with Tofacitinib

Tofacitinib, as a JAK inhibitor, is classified as carrying a low risk (<1%) for HBV reactivation in patients with resolved HBV infection (HBsAg-negative, anti-HBc-positive) 1. However, the risk may be higher in:

• Patients with detectable HBV DNA
• Patients with negative anti-HBs (antibody to hepatitis B surface antigen)
• Patients receiving multiple immunosuppressive medications
• Patients with hematological diseases

Management Based on Screening Results

If HBsAg-positive OR HBV DNA detected:

• Prophylactic antiviral therapy should be initiated before starting tofacitinib 1
• Preferred antivirals: entecavir, tenofovir disoproxil fumarate, or tenofovir alafenamide (high barrier to resistance) 1
• Antiviral prophylaxis should continue for at least 6 months after discontinuation of tofacitinib 1

If HBsAg-negative but anti-HBc-positive:

• For JAK inhibitor therapy alone, monitoring is generally recommended over prophylaxis 1
• Monitor HBsAg, ALT, and HBV DNA every 1-3 months during therapy 1
• Start antiviral therapy immediately if HBV reactivation is detected 1

Special Considerations

1. Combination Therapy: If tofacitinib will be used with other immunosuppressants, the cumulative risk of HBV reactivation increases and may warrant prophylaxis even in anti-HBc-positive patients 1.

2. Monitoring Protocol: For patients under monitoring (rather than prophylaxis), testing should include:

   • ALT levels
   • HBsAg (to detect seroreversion)
   • HBV DNA (to detect viral replication)

3. Consultation: Consider hepatology consultation for patients with positive HBsAg or anti-HBc to determine optimal management strategy 1.

Clinical Pitfalls to Avoid

• Don't skip screening: Failure to screen can lead to undetected HBV reactivation with potentially fatal consequences 2.
• Don't rely only on HBsAg: Testing only for HBsAg will miss patients with resolved HBV infection who are still at risk for reactivation 3.
• Don't use lamivudine for prophylaxis: Lamivudine has a higher resistance rate; entecavir or tenofovir are preferred 1.
• Don't discontinue monitoring too early: Continue monitoring for at least 6 months after stopping tofacitinib 1.

By following these guidelines, you can effectively prevent the potentially serious complication of HBV reactivation in patients starting tofacitinib therapy.