From the Guidelines
Patients who are hepatitis B core antibody positive and also hepatitis B surface antibody positive should receive prophylactic antiviral therapy when initiating rituximab, as recommended by the most recent guidelines. This is based on the risk of hepatitis B reactivation due to core antibody and surface antigen status and the specific DMARD being initiated, as stated in the 2021 American College of Rheumatology guideline for the treatment of rheumatoid arthritis 1. The guideline strongly recommends prophylactic antiviral therapy over frequent monitoring of viral load and liver enzymes alone for patients initiating rituximab who are hepatitis B core antibody positive, regardless of hepatitis B surface antigen status.
Some key points to consider:
- The presence of surface antibodies provides some protection, but immunosuppression can overcome this immunity, making vigilant monitoring essential for early intervention if needed.
- Regular monitoring of liver function tests and HBV DNA levels every 1-3 months during and for 6-12 months after rituximab therapy is appropriate.
- If viral reactivation occurs (indicated by detectable HBV DNA or rising levels), antiviral prophylaxis with entecavir 0.5mg daily or tenofovir 300mg daily should be initiated promptly and continued for at least 6 months after rituximab discontinuation.
- The 2022 KASL clinical practice guidelines for management of chronic hepatitis B also recommend prophylactic antiviral therapy for patients who are HBsAg-negative, HBV DNA-undetectable, and anti-HBc-positive, and are receiving rituximab or other B-cell depleting agents 1.
- The 2020 ASCO provisional clinical opinion update also recommends anti-HBV prophylaxis for patients receiving anti-CD20 antibody therapy (eg, rituximab) or undergoing stem-cell transplantation, even if they are HBsAg-negative and anti-HBc-positive 1.
Overall, the most recent and highest quality evidence suggests that prophylactic antiviral therapy is necessary for patients who are hepatitis B core antibody positive and also hepatitis B surface antibody positive when receiving rituximab, in order to prevent hepatitis B reactivation and its associated morbidity and mortality.
From the FDA Drug Label
Screen all patients for HBV infection by measuring HBsAg and anti-HBc before initiating treatment with RITUXAN For patients who show evidence of prior hepatitis B infection (HBsAg positive [regardless of antibody status] or HBsAg negative but anti-HBc positive), consult with physicians with expertise in managing hepatitis B regarding monitoring and consideration for HBV antiviral therapy before and/or during RITUXAN treatment Reactivation also has occurred in patients who appear to have resolved hepatitis B infection (i.e., HBsAg negative, anti-HBc positive and hepatitis B surface antibody [anti-HBs] positive)
Hepatitis B core antibody positive patients who are also hepatitis B surface antibody positive may still be at risk for HBV reactivation when receiving rituximab.
- These patients should be monitored for clinical and laboratory signs of hepatitis or HBV reactivation during and for several months following RITUXAN therapy.
- Consultation with physicians with expertise in managing hepatitis B is recommended to consider HBV antiviral therapy before and/or during RITUXAN treatment 2.
From the Research
Hepatitis B Core Antibody Positive and Surface Antibody Positive Patients Receiving Rituximab
- The need for therapy in hepatitis B core antibody positive patients who are also hepatitis B surface antibody positive and are receiving rituximab is a complex issue.
- According to the study 3, patients who are hepatitis B surface antigen negative and anti-hepatitis B core antibody positive are at risk of HBV reactivation when receiving rituximab-containing combination chemotherapy without antiviral prophylaxis.
- However, the study 3 also found that the rate of HBV reactivation is low in patients who are HBsAg negative/anti-HBc positive receiving rituximab-based combination chemotherapy without concomitant antiviral prophylaxis, particularly in those with anti-HBs.
- The study 4 recommends that HBsAg-negative, anti-HBc positive carriers, i.e., those with resolved HBV infection, should receive universal prophylaxis with lamivudine for those with onco-hematological diseases.
- The study 5 found that the presence of HBsAb seems to protect from clinical HBV reactivation related to DAA therapy, and that the most pronounced prevention for reactivation may require titres greater than 30 iU/L.
- It is essential to note that the studies 3, 4, and 5 do not directly address the specific scenario of hepatitis B core antibody positive patients who are also hepatitis B surface antibody positive and are receiving rituximab.
- However, based on the available evidence, it can be inferred that the risk of HBV reactivation in hepatitis B core antibody positive patients who are also hepatitis B surface antibody positive and are receiving rituximab may be low, particularly if they have a high titre of HBsAb.
Risk Factors for HBV Reactivation
- Elderly patients, particularly those without anti-HBs, seem to be at a higher risk of HBV reactivation 3.
- The study 6 found that an age ≥65 years and an advanced disease stage were independent risk factors for poorer overall survival.
- The presence of HBsAb seems to protect from clinical HBV reactivation related to DAA therapy, and that the most pronounced prevention for reactivation may require titres greater than 30 iU/L 5.
Monitoring and Prophylaxis
- The study 4 recommends that prior to starting RTX treatment, all patients should be screened for HBV infection.
- The study 6 suggests that the duration of regular liver function monitoring for more than 1 year after immunosuppressive therapy or after withdrawal of prophylactic antiviral therapy should be prolonged.
- The study 5 found that the presence of HBsAb seems to protect from clinical HBV reactivation related to DAA therapy, and that the most pronounced prevention for reactivation may require titres greater than 30 iU/L.