What pre‑biologic workup and baseline screening should be performed before initiating rituximab therapy?

Pre-Biologic Workup for Rituximab

Before initiating rituximab, you must screen for hepatitis B virus infection (HBsAg and anti-HBc), hepatitis C virus infection, latent tuberculosis, obtain a complete blood count with differential, and measure baseline immunoglobulin levels (IgG, IgA, IgM). 1, 2

Mandatory Infectious Disease Screening

Hepatitis B Virus (Critical Priority)

• Screen all patients with both HBsAg and anti-HBc before initiating rituximab 2
• Rituximab carries a high risk of hepatitis B reactivation, classified as a high-risk immunosuppressive agent 1
• For patients who are HBsAg-positive OR anti-HBc positive (regardless of HBsAg status): initiate prophylactic antiviral therapy (entecavir or tenofovir) rather than monitoring alone 1, 3
• Start antiviral prophylaxis 2-4 weeks before rituximab initiation 1
• Continue antiviral prophylaxis for 12 months after the last rituximab dose (not just 6 months as with other immunosuppressants), as HBV reactivation can occur up to 1-2 years after rituximab discontinuation 1

Hepatitis C Virus

• Screen for hepatitis C antibodies before initiating therapy 1, 3

Latent Tuberculosis

• Perform latent TB screening before rituximab initiation 1, 3

Baseline Laboratory Testing

Complete Blood Count

• Obtain CBC with differential and platelet count prior to the first dose 2
• This establishes baseline values for monitoring cytopenias, which are a known toxicity of rituximab 1

Immunoglobulin Levels

• Measure baseline serum IgG, IgA, and IgM levels before starting rituximab 3, 4, 5
• Pre-existing hypogammaglobulinemia (IgG <6 g/L) predicts increased risk of developing severe hypogammaglobulinemia and serious infections after rituximab 3, 4
• Baseline IgG levels correlate with post-rituximab hypogammaglobulinemia risk 3
• This is particularly important as hypogammaglobulinemia can persist long-term and may require immunoglobulin replacement therapy 4, 6

Vaccination Strategy

Timing Considerations

• Administer all indicated vaccines BEFORE starting rituximab whenever possible 1
• Vaccine responses are severely impaired for 1-6 months after rituximab, with humoral responses to influenza and pneumococcal vaccines particularly affected 1
• If patients are already on rituximab, vaccines should be given at least 6 months after the start but 4 weeks before the next course 1

Priority Vaccinations to Check/Administer

• Pneumococcal vaccine (PCV followed by PPSV23) 1
• Influenza vaccine (annual) 1
• Hepatitis B vaccine (if non-immune) 1
• Tetanus toxoid 1
• Haemophilus influenzae b 1
• Hepatitis A 1
• Neisseria meningitides 1
• Rubella (for women of childbearing age) 1

Live Vaccines

• Herpes zoster vaccination may be considered, but only in less severely immunosuppressed patients and only if varicella zoster antibody positive 1
• Live vaccines should generally be withheld once rituximab is started 1

Additional Screening Considerations

Cardiovascular Assessment

• Patients with clinically significant cardiovascular disease require special consideration for infusion protocols 2

Pregnancy Status

• Screen for pregnancy before initiating rituximab 5

Hypersensitivity History

• Screen for hypersensitivity to murine proteins 5

Congestive Heart Failure

• Assess for presence of congestive heart failure 5

Common Pitfalls to Avoid

• Do not rely on HBsAg alone for hepatitis B screening—you must also check anti-HBc, as patients with resolved HBV infection (HBsAg-negative/anti-HBc positive) remain at risk for reactivation with rituximab 1
• Do not delay vaccination until after rituximab is started—vaccine responses will be severely impaired for months after B-cell depletion 1
• Do not skip baseline immunoglobulin measurements—pre-existing hypogammaglobulinemia significantly increases infection risk and may require closer monitoring or immunoglobulin replacement 3, 4
• Do not use standard 6-month antiviral prophylaxis duration—rituximab requires 12 months (potentially up to 24 months) of prophylaxis due to prolonged B-cell depletion 1