What are the considerations for using Ocrevus (ocrelizumab) in patients with a history of Hepatitis B?

Management of Hepatitis B in Patients Receiving Ocrevus (Ocrelizumab)

Key Recommendation

All patients with a history of hepatitis B (HBsAg-positive or HBsAg-negative/anti-HBc-positive) must receive antiviral prophylaxis before starting Ocrevus therapy, as ocrelizumab is contraindicated in patients with active HBV infection. 1

Screening Requirements

• Hepatitis B screening is mandatory before initiating Ocrevus therapy 1
• Required screening tests:
  • Hepatitis B surface antigen (HBsAg)
  • Hepatitis B core antibody (anti-HBc)
  • HBV DNA (if either HBsAg or anti-HBc is positive) 2

Risk Assessment

Ocrelizumab is classified as a high-risk agent for HBV reactivation:

• B cell-depleting agents like ocrelizumab pose >10% risk of HBV reactivation in HBsAg-positive patients 2
• B cell-depleting agents also pose >10% risk of reactivation in HBsAg-negative/anti-HBc-positive patients 2
• Recent evidence shows 28.6% reactivation rate in patients with resolved HBV who did not receive prophylaxis 3

Management Algorithm Based on HBV Status

1. HBsAg-Positive Patients

• Action: Contraindicated for Ocrevus treatment unless treated 1
• Must receive antiviral prophylaxis with high barrier to resistance agents (entecavir or tenofovir) 2
• Start antiviral therapy at least 1-4 weeks before first Ocrevus dose 2
• Continue antiviral therapy for at least 12 months after discontinuation of Ocrevus 2

2. HBsAg-Negative/Anti-HBc-Positive Patients (Resolved or Occult HBV)

• Action: Antiviral prophylaxis strongly recommended 2
• Use high genetic barrier antivirals (entecavir or tenofovir) 2
• Start prophylaxis before Ocrevus initiation (recommended ~4 weeks prior) 4
• Continue prophylaxis for at least 12 months after discontinuation of Ocrevus 2
• Pay special attention to patients with low anti-HBs titers (<100 mIU/mL) who are at higher risk of reactivation 3

3. HBsAg-Negative/Anti-HBc-Negative Patients

• Action: May proceed with Ocrevus therapy
• Consider HBV vaccination if not previously vaccinated

Choice of Antiviral Agents

• Preferred agents: High genetic barrier antivirals 2

  • Entecavir
  • Tenofovir disoproxil fumarate (TDF)
  • Tenofovir alafenamide (TAF)

• Not recommended: Lamivudine (due to high resistance rates with prolonged use) 2

Monitoring During Treatment

For patients on antiviral prophylaxis:

• Monitor liver function tests every 3 months
• Check HBV DNA levels every 3-6 months 2

For patients not on prophylaxis (not recommended):

• Monthly monitoring of ALT and HBV DNA required 2
• Immediate initiation of antiviral therapy if reactivation detected

Special Considerations

• Patients with cirrhosis require indefinite antiviral therapy regardless of Ocrevus treatment 2
• Patients with low anti-HBs titers (<100 mIU/mL) have higher reactivation risk and should definitely receive prophylaxis 3
• Consider hepatology consultation for complex cases (cirrhosis, prior treatment failure)

Potential Pitfalls and Caveats

1. Failure to screen: Ocrevus is absolutely contraindicated in active HBV infection; failure to screen could lead to fatal hepatitis 1

2. Inadequate duration of prophylaxis: Reactivation can occur even after Ocrevus discontinuation due to prolonged B-cell depletion; prophylaxis must continue for at least 12 months after last dose 2

3. Using lamivudine for long-term prophylaxis: High resistance rates make it unsuitable; always use high genetic barrier antivirals 2

4. Overlooking patients with resolved infection: HBsAg-negative/anti-HBc-positive patients still require prophylaxis due to high reactivation risk with B-cell depleting therapies 2, 3

5. Stopping monitoring too early: B-cell recovery may take years after discontinuing Ocrevus; extended monitoring is necessary 2