From the Guidelines
Medications with a high risk of hepatitis B reactivation include B-cell depleting agents, such as rituximab, and other immune-related therapies, including high-dose corticosteroids, anthracycline derivatives, and potent TNFα inhibitors, as outlined in the 2022 clinical practice guidelines for management of chronic hepatitis B 1. These medications can cause reactivation rates of ≥10% in HBsAg-positive patients, and include:
- B-cell depleting agents (rituximab, ofatumumab, natalizumab, alemtuzumab, ibritumomab, and obinutuzumab)
- Human immunoglobulin G1 monoclonal antibody targeting CD38-expressing cells (daratumumab)
- High-dose corticosteroids (prednisone ≥20 mg/day, ≥4-week)
- Anthracycline derivatives (doxorubicin, daunorubicin, and epirubicin)
- Potent TNFα inhibitors (infliximab, adalimumab, certolizumab, and golimumab)
- Local therapy for HCC (TACE)
- Chimeric antigen receptor (CAR) T cell therapy Patients requiring these medications should undergo HBV screening before starting therapy, and those with evidence of current or past infection should receive prophylactic antiviral therapy, as recommended by the guidelines 1. Key points to consider:
- HBV reactivation can lead to fulminant hepatitis and death if not prevented or treated promptly
- Prophylaxis should continue during immunosuppressive therapy and for 6-12 months after completion, with longer durations needed for rituximab due to its prolonged immunosuppressive effects
- Moderate-risk medications, such as lower-dose corticosteroids, methotrexate, azathioprine, and other immunosuppressants, also require careful consideration and monitoring for HBV reactivation 1
From the FDA Drug Label
- 3 Hepatitis B Virus (HBV) Reactivation Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure and death, can occur in patients treated with drugs classified as CD20-directed cytolytic antibodies, including RITUXAN Cases have been reported in patients who are hepatitis B surface antigen (HBsAg) positive and also in patients who are HBsAg negative but are hepatitis B core antibody (anti-HBc) positive. 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).
Rituximab (IV) has a high risk of Hepatitis B reactivation.
- Patients who are HBsAg positive or HBsAg negative but anti-HBc positive are at risk of HBV reactivation.
- HBV reactivation can occur up to 24 months following completion of RITUXAN therapy 2.
- Patients who develop HBV reactivation should have RITUXAN immediately discontinued and receive appropriate treatment.
From the Research
Medications with High Risk of Hepatitis B Reactivation
- Rituximab has been associated with an increased risk of hepatitis B virus (HBV) reactivation in patients who are hepatitis B surface antigen (HBsAg) negative and antihepatitis B core antibody (anti-HBc) positive 3, 4, 5
- The risk of HBV reactivation is higher in patients receiving rituximab-based combination chemotherapy without concomitant antiviral prophylaxis 3, 4
- Elderly patients, particularly those without anti-HBs, are at a higher risk of HBV reactivation 3
- Patients with hematologic diseases, such as B-cell lymphoma, are at a higher risk of HBV reactivation when receiving rituximab-containing combination chemotherapy 4, 5
- The cumulative rituximab dose may also play a role in HBV reactivation, with higher doses tend to be associated with a higher risk of reactivation 5
Chemotherapy Regimens with High Risk of Hepatitis B Reactivation
- R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy regimen has been associated with a high risk of HBV reactivation 3, 6
- Other chemotherapy regimens, such as rituximab with cyclophosphamide, vincristine, and prednisone, may also carry a risk of HBV reactivation 3
Prevention of Hepatitis B Reactivation
- Antiviral prophylaxis, such as entecavir, can potentially prevent rituximab-associated HBV reactivation in patients with lymphoma and resolved hepatitis B 6, 7
- Entecavir has been shown to be more effective than lamivudine in preventing HBV reactivation in patients with diffuse large B-cell lymphoma undergoing R-CHOP chemotherapy 6