What vaccinations should be administered before initiating rituximab treatment for neuromyelitis optica?

Vaccinations Before Rituximab for NMO

All non-live vaccinations should be administered at least 2 weeks before initiating rituximab for neuromyelitis optica, with rituximab then delayed for at least 2 weeks after vaccination to allow adequate immune response development.

Core Vaccination Strategy

The 2022 American College of Rheumatology guidelines provide the clearest framework: whenever possible, vaccinations should be administered prior to rituximab initiation, and rituximab should be delayed for at least 2 weeks after any vaccination to allow time for immune response development 1. This principle applies universally to NMO patients, as rituximab profoundly blunts vaccine immunogenicity once B-cell depletion occurs.

Essential Vaccinations to Complete

High Priority Vaccines

• Pneumococcal vaccination: Use PCV13 (preferred over PPSV23 due to better response in immunosuppressed patients). Rituximab significantly blunts pneumococcal vaccine responses 1
• Influenza vaccine: Annual vaccination (though this can be given on schedule even after rituximab initiation if timing doesn't align)
• Hepatitis B series: Complete the full series, particularly important for patients who may require future immunosuppression
• Meningococcal vaccines: Critical given the risk if patients later transition to complement inhibitors (eculizumab, ravulizumab). One case report documented fatal meningococcal sepsis in an NMOSD patient who received ravulizumab post-rituximab despite prior vaccination 2
• COVID-19 vaccination: Complete primary series and boosters

Additional Recommended Vaccines

• Hepatitis A: Particularly for liver disease risk factors
• Tdap/Td: Ensure up-to-date tetanus/diphtheria/pertussis coverage
• Herpes zoster (Shingrix): The recombinant vaccine is non-live and safe; consider for patients ≥50 years or those with prior varicella infection

Critical Timing Considerations

The optimal window is to vaccinate at least 2-4 weeks before rituximab initiation. This allows:

• Adequate time for immune response development (minimum 2 weeks)
• Verification of response if needed
• No delay in urgent NMO treatment if disease activity is severe

When Disease Activity is High

If NMO disease activity is severe with risk of irreversible neurological deficits, do not delay rituximab initiation for vaccination completion 3. In this scenario:

• Initiate rituximab promptly to prevent disability
• Administer vaccines after rituximab with understanding of reduced efficacy
• Consider revaccination later when B-cells recover (though this may not occur with maintenance rituximab)

Contraindicated Vaccines

Live vaccines are absolutely contraindicated once rituximab is initiated and should be avoided within 4 weeks before starting treatment 4. These include:

• MMR (measles, mumps, rubella)
• Varicella (VAR)
• Zoster live vaccine (Zostavax - not Shingrix)
• Yellow fever
• Intranasal influenza

Concurrent Glucocorticoid Considerations

Many NMO patients receive high-dose steroids during acute attacks. If patients are on prednisone ≥20 mg daily:

• Influenza vaccine should still be given 1
• Other non-live vaccines should ideally be deferred until steroids are tapered to <20 mg daily if clinically feasible
• If vaccination cannot be delayed, administer anyway as some immunity is better than none

Infection Prophylaxis Post-Rituximab

Once rituximab is initiated, the FDA label recommends 5:

• PCP prophylaxis: Consider during treatment and for at least 6 months following the last rituximab infusion (based on GPA/MPA data)
• Herpes virus prophylaxis: Consider based on individual risk factors

Common Pitfalls to Avoid

1. Waiting to vaccinate until after rituximab: Once B-cells are depleted, vaccine responses are severely impaired
2. Assuming vaccines can be "caught up" later: Maintenance rituximab maintains B-cell depletion indefinitely
3. Forgetting meningococcal vaccination: Critical if future treatment escalation to complement inhibitors is possible
4. Delaying urgent rituximab for non-urgent vaccines: Preventing irreversible NMO disability takes precedence

Practical Algorithm

For newly diagnosed NMO patients:

1. Assess vaccination status immediately upon diagnosis
2. If disease is stable: Complete all indicated vaccines → wait 2 weeks → initiate rituximab
3. If disease is active with high relapse risk: Initiate rituximab promptly → vaccinate during treatment with reduced expectations
4. Document vaccination status and plan for monitoring/revaccination if B-cells recover