Which immunosuppressive drugs can contribute to the reactivation of HBV?
Certain biologic disease-modifying antirheumatic drugs (bDMARDs) have been associated with HBV reactivation. Rituximab appears to pose the highest risk among available immunosuppressive agents. Overall the risk for reactivation of HBV with rituximab is thought to be lower in doses used to treat rheumatic conditions than chemotherapy regimens (e.g., lymphoma). Before prescribing bDMARDs, it is prudent to screen for HBV infection by testing for HBsAb, HBcAb, and HBsAg. Non-bDMARDs and low-dose prednisone are considered low risk for reactivation, but screening patients on these medications to risk stratify is reasonable as well. Expert recommendations suggest that certain patient populations may benefit from prophylactic antiviral therapy.
- Past (resolved) infection (HBsAg–, HBcAb+, HBsAb+/–)
- • Anti-tumor necrosis factor (TNF) therapy (and other bDMARDs use) is associated with a low risk of reactivation; periodic monitoring of liver enzymes and viral load is recommended.
- • Rituximab is associated with a higher risk of reactivation in this setting. In dosing associated with malignancy, prophylactic antiviral therapy is recommended (risk of reactivation 15% untreated). In dosing regimens associated with rheumatic disease, the risk is lower (~1%); monitoring with serial liver enzymes and viral load is recommended (some experts consider prophylactic antiviral therapy in this setting as well).
- Chronic HBV/inactive carrier (HBsAg+, HBcAb +, HBsAb–; normal liver function tests [LFTs], undetectable viral load)
- • Anti-TNF therapy is associated with a moderate risk of reactivation (estimated at 1%–10%); prophylactic antiviral therapy recommended
- • Rituximab is associated with a high risk of reactivation (estimated at >10%); prophylactic antiviral therapy recommended
- • Risk with other bDMARDs uncertain based on limited studies; reactivation has been reported with abatacept and ustekinumab in this setting; therefore, experts recommend treating these agents similar to those on anti-TNF therapy
- Chronic active HBV (HBsAg+, HBcAb +, HBsAb–; elevated LFTs and viral load)
- • Require antiviral therapy for active HBV regardless of the type of immunosuppressive agent
