In a patient who received pneumococcal vaccination one year before starting rituximab and is now due for a maintenance rituximab infusion, should I administer a pneumococcal booster now (at least two weeks before the infusion) and which other inactivated vaccines are indicated?

Pneumococcal Booster and Vaccination Strategy for Rituximab Maintenance

Yes, administer a pneumococcal booster now, timing it to coincide with when your next rituximab infusion is due, then delay the rituximab dose by at least 2 weeks after vaccination to optimize immune response. 1, 2

Optimal Vaccination Timing for Rituximab Patients

For non-influenza inactivated vaccines (including pneumococcal boosters), the American College of Rheumatology conditionally recommends deferring vaccination until the next rituximab administration is due, then delaying rituximab for at least 2 weeks after vaccination. 1 This strategy exploits the period of maximal B-cell recovery that occurs just before the next scheduled rituximab infusion, thereby improving vaccine immunogenicity. 2

Why This Timing Matters

• Rituximab causes profound B-cell depletion that markedly impairs vaccine-induced antibody responses for up to 6 months after each infusion. 2, 3, 4
• Studies demonstrate that only 19% of rituximab-treated patients achieve satisfactory pneumococcal antibody responses (defined as ≥2-fold increase in antibody concentrations in ≥6 serotypes) compared to 61% of controls. 1
• Research shows that 21% of rituximab-treated patients achieved fourfold increases in anti-pneumococcal antibodies at 6 months post-rituximab versus 67% in placebo groups. 3
• Prior vaccinations may not provide lasting protection, as rituximab can deplete existing antibody-producing plasma cells over time. 2

Pneumococcal Vaccination Recommendations

Since you received pneumococcal vaccination 1 year ago, you are now due for your PPSV23 booster if you initially received PCV13. 1

Standard Pneumococcal Series

• The recommended sequence is one dose of PCV13 followed by PPSV23 at least 8 weeks later. 1
• A second PPSV23 dose should be given 5 years after the first PPSV23 dose. 1
• If your initial vaccination 1 year ago was PCV13 alone, you need PPSV23 now. 1
• If you completed both vaccines 1 year ago, no booster is needed until 5 years after the first PPSV23. 1

Other Indicated Inactivated Vaccines

The following inactivated vaccines should be administered using the same timing strategy (just before next rituximab dose, then delay rituximab ≥2 weeks): 1, 2

Annual Influenza Vaccine

• Exception to the timing rule: administer annual inactivated influenza vaccine on schedule without delaying for rituximab timing, because its seasonal public-health importance outweighs reduced immunogenicity. 1, 2
• Only inactivated (intramuscular) formulation should be used; live attenuated intranasal influenza vaccine is contraindicated. 2, 5
• Consider high-dose quadrivalent vaccine for patients over 65 or all immunocompromised patients for improved response. 1

Tetanus-Diphtheria-Pertussis (Tdap)

• Ensure tetanus toxoid vaccination is up to date (every 10 years). 1, 6
• Recall responses to tetanus toxoid (T-cell dependent antigen) are relatively preserved even in rituximab-treated patients, with 39% achieving ≥4-fold rise compared to 42% in controls. 7

Hepatitis B Vaccine

• Recommended for all nonimmune adults at risk for HBV infection. 1
• Particularly important given that rituximab FDA labeling strongly recommends prophylactic antiviral therapy before initiating rituximab in patients who are hepatitis B core antibody positive. 5

COVID-19 Vaccines

• Administer as per general population guidelines, using the same timing strategy as other non-influenza inactivated vaccines. 1

Contraindicated Vaccines During Rituximab

Live attenuated vaccines must not be administered during rituximab therapy or within 6 months after the last rituximab dose because of severe immunosuppression. 2, 5 This includes:

• MMR (measles-mumps-rubella) 2, 6
• Varicella (chickenpox) 2, 6
• Zoster live vaccine (Zostavax) 2
• Live attenuated intranasal influenza vaccine 2, 5

Recombinant Zoster Vaccine Exception

• Recombinant zoster vaccine (Shingrix) is inactivated and can be given using the standard timing strategy for non-influenza vaccines. 1

Monitoring Vaccine Response

Measure specific antibody titers approximately 4 weeks after vaccination to verify adequate immune response. 2, 6

• For pneumococcal vaccine, measure serotype-specific antibodies. 2, 6
• If titers are insufficient, consider revaccination after rituximab discontinuation or during a prolonged treatment holiday, though evidence for this approach is limited. 2
• Studies show that 55% of rituximab-treated patients had total absence of influenza-specific IgG production when vaccinated 6 months post-rituximab. 4

Critical Pitfalls to Avoid

Do not vaccinate immediately after a rituximab infusion. 1, 2 The period immediately following rituximab administration represents the nadir of B-cell function, resulting in minimal to no vaccine response. 3, 4, 8

Do not skip the 2-week delay of rituximab after vaccination. 1, 2 This delay is essential to allow time for antibody development before the next cycle of B-cell depletion. 2

Do not assume prior vaccinations provide adequate protection. 2 Rituximab can deplete existing antibody-producing plasma cells, potentially reducing protection from vaccines given before rituximab initiation. 2

Glucocorticoid Considerations

If you are taking concurrent glucocorticoids, vaccine response may be further impaired:

• Low-dose glucocorticoids (prednisone ≤10 mg daily) do not significantly impact vaccine response when combined with rituximab. 1
• High-dose glucocorticoids (prednisone ≥20 mg daily) may adversely impact pneumococcal vaccine immunogenicity. 1
• For patients on prednisone ≥20 mg daily, deferring non-influenza vaccinations until glucocorticoids are tapered to <20 mg daily is conditionally recommended. 1