What is the recommended timing for administering vaccines before starting Rituximab (rituximab) therapy?

Vaccines Before Rituximab

Administer all indicated vaccines at least 2-4 weeks before initiating rituximab therapy, with optimal timing being 4-6 weeks prior to the first infusion to maximize immune response. 1, 2

Essential Vaccines to Administer Pre-Rituximab

Pneumococcal Vaccination (Highest Priority)

• Administer PCV13 (13-valent pneumococcal conjugate vaccine) first, followed by PPV23 (23-valent pneumococcal polysaccharide vaccine) 8 weeks later 1
• If time is limited, give PCV13 at minimum 2-4 weeks before rituximab and plan PPV23 for the next rituximab cycle 1
• Both vaccines should ideally be completed before rituximab whenever possible 2, 1
• Dosing: 0.5 mL intramuscular or subcutaneous injection for both vaccines 1

Influenza Vaccination

• Administer seasonal inactivated influenza vaccine (quadrivalent) annually 1
• Use only inactivated (non-live) influenza vaccine, never live attenuated influenza vaccine (LAIV) 3, 4
• Dosing: 0.5 mL intramuscular injection 1
• Timing: At least 2-4 weeks before rituximab initiation 1

Tetanus Toxoid

• Ensure Tdap (tetanus, diphtheria, acellular pertussis) is up to date 1
• Administer if not received within past 10 years 1
• Dosing: 0.5 mL intramuscular injection 1
• Critical caveat: Rituximab severely impairs tetanus toxoid responses for at least 6 months; patients with contaminated wounds during this period require tetanus immunoglobulin in addition to vaccine 3, 5

Hepatitis B Vaccination

• Complete series if patient lacks documented immunity 1
• Optimal timing: Begin 8-12 weeks before rituximab to allow for multi-dose series 1

Additional Vaccines to Consider Based on Risk

Live Vaccines (Must Be Given BEFORE Rituximab)

• MMR (measles, mumps, rubella): Administer at least 4 weeks before rituximab if patient lacks documented immunity 1, 3
• Varicella vaccine: Give at least 4 weeks before rituximab if seronegative 3
• Live vaccines are absolutely contraindicated once rituximab is started and for 6 months after the last dose 3, 4

Other Non-Live Vaccines

• Hepatitis A: If indicated by risk factors 1
• Meningococcal vaccine: If indicated by risk factors 1
• Inactivated typhoid vaccine (Vi polysaccharide): 0.5 mL intramuscular, repeat every 3 years if indicated 1

Optimal Timing Algorithm

Best-Case Scenario (8-12 Weeks Available)

1. Week 0: Administer PCV13, influenza, Tdap, hepatitis B dose 1, and any indicated live vaccines 1
2. Week 4: Administer MMR or varicella if needed (must be at least 4 weeks before rituximab) 1, 3
3. Week 8: Administer PPV23 and hepatitis B dose 2 1
4. Week 8-12: Initiate rituximab 1

Acceptable Scenario (2-4 Weeks Available)

1. Week 0: Administer PCV13, influenza, and Tdap simultaneously 1
2. Week 2-4: Initiate rituximab 1
3. Plan PPV23 for next rituximab cycle (administer just before next scheduled dose, then delay rituximab by at least 2 weeks) 1, 6

Suboptimal But Necessary (Less Than 2 Weeks)

• If active disease requires urgent rituximab initiation, prioritize disease control over vaccination 2
• Administer whatever vaccines possible, recognizing responses will be suboptimal 2
• Plan comprehensive vaccination at least 6 months after last rituximab dose when B-cell recovery occurs 2

Post-Vaccination Monitoring

Measure antibody titers 4 weeks after vaccination to confirm adequate response 1:

• Pneumococcal serotype-specific antibodies
• Tetanus antibodies
• Hepatitis B surface antibodies
• Other vaccine-specific antibodies as indicated

This monitoring is critical because rituximab profoundly impairs vaccine responses for up to 6 months after treatment 2, 4, 5.

Critical Mechanistic Understanding

Rituximab causes B-cell depletion that typically lasts 6-9 months, with full B-cell recovery usually occurring 9-12 months after therapy 7, 8. During this period:

• Humoral (antibody) responses to vaccines are severely impaired 2, 4, 5
• Cellular immune responses are also reduced in parallel with depleted B-cell pools 5
• Patients vaccinated before rituximab initiation achieve significantly higher seroconversion rates (87-91%) compared to those vaccinated after rituximab (61-65%) 8

Common Pitfalls to Avoid

1. Never administer live vaccines after rituximab has been started - the immunosuppressive effect lasts at least 6 months after the last dose 3, 4
2. Do not assume vaccine responses are adequate without checking titers - up to 79% of rituximab-treated patients fail to mount adequate antibody responses to pneumococcal vaccine 1, 5
3. Do not delay rituximab indefinitely for vaccination if disease is active - active underlying disease takes priority over vaccination 2
4. Remember that vaccine impairment is reversible - adequate vaccination 9 months or more after rituximab cessation can restore responses comparable to healthy controls 8

Special Considerations for COVID-19 Vaccination

• Patients receiving COVID-19 vaccines more than 6 months after rituximab have significantly better serological responses and reduced hospitalization risk (adjusted OR 0.22) 9
• mRNA COVID-19 vaccines are preferred over adenoviral vector vaccines in rituximab-treated patients 9
• Booster vaccinations independently reduce COVID-19 hospitalization risk (adjusted OR 0.31) 9