What vaccinations should be given to Rheumatoid Arthritis (RA) patients before starting Rituximab (rituximab) therapy in the Indian setting, and what are their dosing recommendations?

Pre-Rituximab Vaccination Protocol for Rheumatoid Arthritis Patients in India

Before starting rituximab therapy in RA patients, administer pneumococcal and influenza vaccines at least 2 weeks prior to the first rituximab infusion to maximize immune response, as rituximab severely impairs vaccine responses for up to 6 months after treatment. 1

Essential Vaccinations Before Rituximab Initiation

Pneumococcal Vaccination (Highest Priority)

• Administer 13-valent pneumococcal conjugate vaccine (PCV13) first, followed by 23-valent pneumococcal polysaccharide vaccine (PPV23) 8 weeks later 2
• PCV13 dosing: Single 0.5 mL intramuscular injection 2
• PPV23 dosing: Single 0.5 mL intramuscular or subcutaneous injection 1
• Rituximab reduces pneumococcal vaccine response dramatically—only 10.3% of patients on rituximab monotherapy achieve adequate response to both serotypes compared to 50% on other biologics 3
• Complete both pneumococcal vaccines before rituximab whenever possible 1, 4

Influenza Vaccination

• Administer seasonal inactivated influenza vaccine annually 1
• Dosing: Single 0.5 mL intramuscular injection of quadrivalent inactivated vaccine 1
• If rituximab cannot be delayed, give influenza vaccine on schedule rather than deferring, as seasonal timing is critical 1
• Rituximab causes 55% of patients to have complete absence of influenza-specific IgG production 5
• Never use live attenuated influenza vaccine (nasal spray) in patients planned for rituximab 6

Tetanus-Diphtheria-Pertussis (Tdap/Td)

• Ensure tetanus toxoid vaccination is up to date 1
• Dosing: Single 0.5 mL intramuscular injection of Tdap if not received in past 10 years 1
• Tetanus responses are preserved at 6 months post-rituximab but reduced in the first month 1, 4
• Important caveat: If patient develops contaminated wound within 6 months of rituximab, administer tetanus immunoglobulin (250-500 units IM) in addition to vaccine 1

Hepatitis B Vaccination (If Not Previously Vaccinated)

• Screen for hepatitis B surface antigen, surface antibody, and core antibody before rituximab 7
• If hepatitis B core antibody positive, strongly recommend prophylactic antiviral therapy before rituximab 7
• If non-immune, administer hepatitis B vaccine series: 0,1, and 6 months schedule with 1.0 mL (20 mcg) intramuscular injections 1
• Complete series before rituximab initiation as responses are significantly reduced on rituximab 1

Additional Vaccinations to Consider in Indian Context

Varicella Zoster Virus (VZV) Vaccination

• Assess VZV infection and vaccination history 1
• If negative history for chickenpox or vaccination, administer 2 doses of varicella vaccine (0.5 mL subcutaneous) 4-8 weeks apart BEFORE rituximab 1
• Critical timing: Complete at least 4 weeks before rituximab initiation, as this is a live vaccine contraindicated once rituximab starts 6

Measles-Mumps-Rubella (MMR)

• If patient lacks documented immunity, administer MMR booster (0.5 mL subcutaneous) at least 4 weeks before rituximab 1
• Absolutely contraindicated once rituximab is started 6

Typhoid Vaccination (India-Specific)

• Use inactivated typhoid vaccine (Vi polysaccharide), NOT live oral vaccine 1
• Dosing: Single 0.5 mL intramuscular injection, repeat every 3 years 1

Critical Timing Algorithm

Optimal Scenario (8-12 weeks before rituximab):

1. Week 0: PCV13 + Influenza + Tdap + Hepatitis B (dose 1) + Typhoid
2. Week 4: Live vaccines if needed (VZV, MMR) - only if patient not yet on high-dose immunosuppression
3. Week 8: PPV23 + Hepatitis B (dose 2)
4. Week 10-12: Initiate rituximab (at least 2 weeks after last vaccine) 1

Suboptimal but Acceptable (2-4 weeks before rituximab):

1. Give PCV13 + Influenza + Tdap simultaneously
2. Wait minimum 2 weeks before rituximab 1
3. Plan PPV23 for next rituximab cycle (give just before next dose is due) 1

If Rituximab Cannot Be Delayed:

• Give influenza vaccine on schedule even if rituximab already started 1
• Defer other non-live vaccines until next rituximab dose is due, then give 2 weeks before next infusion 1

Contraindicated Vaccines on Rituximab

Never administer these live vaccines once rituximab is started or within 6 months after last dose: 6

• MMR vaccine
• Varicella (chickenpox) vaccine
• Herpes zoster live vaccine (Zostavax)
• Yellow fever vaccine
• Oral polio vaccine
• BCG vaccine
• Live attenuated influenza vaccine (nasal)
• Oral typhoid vaccine

Post-Vaccination Antibody Monitoring

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

• Pneumococcal serotype-specific antibodies (especially if patient already on methotrexate) 1
• Consider checking tetanus, hepatitis B antibodies if high-risk patient 1
• If inadequate response before rituximab, consider revaccination or alternative strategies 1

Common Pitfalls to Avoid

• Do not assume patients on methotrexate will respond normally to vaccines—methotrexate reduces pneumococcal vaccine response, so check titers 1
• Do not give live vaccines to patients already on prednisone ≥20 mg/day or high-dose DMARDs—they are already too immunosuppressed 1
• Do not start rituximab immediately after vaccination—wait minimum 2 weeks to allow immune response development 1
• Do not forget to counsel patients about avoiding live vaccines for 6 months after rituximab 6
• Do not use PPV23 alone—prime with PCV13 first for better response in immunosuppressed patients 2