Praxis Medical Insights

Est. 2024 • Clinical Guidelines Distilled

Made possible by volunteer editors from the University of Calgary & University of Alberta

Last Updated: 9/23/2025

Pre-Rituximab Screening and Management

Mandatory Pre-Treatment Laboratory Testing

  • The American College of Rheumatology strongly recommends hepatitis B virus (HBV) screening with HBsAg, anti-HBc, and anti-HBs before initiating rituximab, due to the high risk of HBV reactivation, which can result in fulminant hepatitis and death 2, 3
  • HBV screening is essential, as rituximab carries the highest risk of HBV reactivation among all immunosuppressive agents, and prophylactic antiviral therapy is strongly recommended for all rituximab patients who are anti-HBc positive, regardless of HBsAg status 2, 3
  • Transaminases (ALT/AST) should be checked at baseline to monitor potential HBV reactivation during therapy 5, 1
  • Serum creatinine and estimated GFR are recommended before starting rituximab, particularly in patients with ANCA-associated vasculitis or other kidney involvement 5, 6

Additional Testing Based on Clinical Context

  • Baseline IgG level should be measured, as low IgG (<3 g/L) predicts greater risk of secondary immunodeficiency with rituximab 6
  • TB screening (interferon-gamma release assay or tuberculin skin test) is recommended unless already performed before other immunosuppressive therapy without subsequent TB exposure 5
  • HIV testing is recommended for patients with HIV risk factors 5

Management Algorithm for HBV Test Results

  • If HBsAg positive, start potent antiviral therapy (entecavir, tenofovir, or tenofovir alafenamide) before rituximab, and continue antiviral for at least 18 months after stopping rituximab 1
  • If HBsAg negative but anti-HBc positive, obtain baseline HBV DNA to rule out occult active infection, and start prophylactic antiviral therapy (entecavir or tenofovir preferred) 1, 2, 3
  • If all HBV tests negative, proceed with rituximab without antiviral prophylaxis, but consider HBV vaccination if anti-HBs is also negative 1, 7

Critical Pitfalls to Avoid

  • The American College of Rheumatology strongly recommends prophylactic antiviral therapy over monitoring for all rituximab patients who are anti-HBc positive, because HBsAg seroreversion is consistently associated with hepatitis flare 2, 3
  • Do not use lamivudine for HBV prophylaxis, as it has high resistance rates; use entecavir, tenofovir, or tenofovir alafenamide instead 1
  • Screen for non-melanoma skin cancer in at-risk patients before starting therapy 5