What vaccines should be administered to a patient prior to starting infliximab (chimeric monoclonal antibody against tumor necrosis factor-alpha)?

Vaccination Before Starting Infliximab

All indicated vaccines should be administered at least 2-4 weeks before initiating infliximab therapy, with live vaccines requiring a minimum 4-week interval, as infliximab severely impairs vaccine responses once treatment begins. 1

Essential Vaccines to Administer Pre-Infliximab

Pneumococcal Vaccination (Highest Priority)

• Administer PCV20 (20-valent pneumococcal conjugate vaccine) as a single dose for pneumococcal vaccine-naïve patients, which eliminates the need for additional PPSV23. 2
• Alternatively, give PCV15 followed by PPSV23 at least 8 weeks later if PCV20 is unavailable. 2
• For patients previously vaccinated with PPSV23, administer PCV20 (preferred) or PCV15. 2
• Dosing: 0.5 mL intramuscular injection. 2

Influenza Vaccination

• Administer inactivated or recombinant influenza vaccine annually, ideally 2-4 weeks before infliximab initiation. 2
• Use high-dose quadrivalent vaccine for patients ≥65 years or consider for all immunocompromised patients. 2
• Never use live attenuated influenza vaccine (LAIV). 2, 1
• Dosing: 0.5 mL intramuscular injection. 2

COVID-19 Vaccination

• Administer updated COVID-19 vaccine at least 2 weeks before initiation of immunosuppressive therapy. 2
• Moderately or severely immunocompromised patients require 2-3 doses of the same brand. 2

Recombinant Zoster Vaccine (RZV)

• Administer RZV (Shingrix) for patients ≥50 years or ≥18 years at increased risk for herpes zoster. 2
• Give 2 doses separated by 2-6 months (or 1-2 months for immunocompromised patients needing shorter schedule). 2
• This is the preferred herpes zoster vaccine as it is non-live and safe in immunosuppression. 2

Tetanus-Diphtheria-Pertussis (Tdap)

• Ensure Tdap is current; administer if not received within past 10 years. 2, 3
• Critical because infliximab impairs tetanus toxoid responses; patients with contaminated wounds during therapy require tetanus immunoglobulin. 3
• Dosing: 0.5 mL intramuscular injection. 2

Hepatitis B Vaccination

• Complete hepatitis B series if patient lacks documented immunity, ideally 8-12 weeks before infliximab to allow for multi-dose series. 3, 1
• Treatment with infliximab significantly reduces HBV vaccine efficacy; only 14% of patients vaccinated after starting infliximab develop protective antibodies compared to 88% vaccinated before therapy. 4
• Screen for hepatitis B infection before starting infliximab per FDA labeling. 1

Additional Vaccines Based on Risk Factors

Haemophilus Influenzae Type b (Hib)

• Consider for patients with planned splenectomy, ideally ≥2 weeks before procedure. 2

Hepatitis A

• Vaccinate patients at risk for HAV exposure (travel to endemic areas, receiving blood products). 2

Human Papillomavirus (HPV)

• Administer per general population guidelines, particularly for patients with systemic lupus erythematosus or other high-risk conditions. 2
• Can be given from age 9 up to age 45. 2

Meningococcal Vaccine

• Consider based on individual risk factors and epidemiologic exposure. 2

Critical Timing Algorithm

Optimal 8-12 Week Pre-Treatment Schedule:

• Week 0: Administer PCV20 (or PCV15), influenza, Tdap, hepatitis B dose 1, and any indicated live vaccines (MMR, varicella if needed). 3
• Week 4: Administer MMR or varicella if needed (must be ≥4 weeks before infliximab). 3
• Week 8: Administer PPSV23 (if using PCV15 strategy) and hepatitis B dose 2. 3
• Week 8-12: Initiate infliximab therapy. 3

Minimum Acceptable Schedule (if time-limited):

• 2-4 weeks before infliximab: Give PCV20, influenza, Tdap, and hepatitis B dose 1 simultaneously. 2, 3
• Plan remaining doses for subsequent infliximab cycles when possible. 3

Contraindicated Vaccines During Infliximab Therapy

Live vaccines are absolutely contraindicated once infliximab is started and should not be given with infliximab. 1

This includes:

• Live attenuated influenza vaccine (LAIV) 2, 1
• MMR (measles-mumps-rubella) 3, 1
• Varicella (chickenpox) 3, 1
• Live zoster vaccine (Zostavax) 2
• Yellow fever 2
• Oral typhoid 2
• BCG 2

Mechanistic Rationale

TNF-alpha inhibitors like infliximab impair both humoral and cell-mediated immune responses to vaccines, with the most profound effects on vaccines requiring T-cell dependent antibody responses. 2, 5

• Infliximab reduces vaccine immunogenicity, though the effect is less severe than with rituximab (B-cell depleting therapy). 2
• Concomitant immunosuppressants (methotrexate, azathioprine) further reduce vaccine responses. 2, 4
• Patients vaccinated before infliximab achieve significantly higher seroconversion rates than those vaccinated during therapy. 3, 4

Post-Vaccination Monitoring

Measure antibody titers 4-6 weeks after vaccination to confirm adequate response, particularly for:

• Pneumococcal serotype-specific antibodies 3
• Hepatitis B surface antibodies 3, 4
• Other vaccine-specific antibodies as clinically indicated 3

Common Pitfalls to Avoid

• Do not delay infliximab indefinitely for vaccination if disease is severe or active—prioritize disease control while administering as many vaccines as feasible. 2, 3
• Do not assume vaccine responses are adequate without checking titers, especially for hepatitis B where failure rates are high. 3, 4
• Do not administer live vaccines after infliximab has started—this creates infection risk with vaccine strains. 1
• Do not forget to update household members' vaccinations, particularly for influenza and other communicable diseases. 2
• Infants exposed to infliximab in utero should wait at least 6 months after birth before receiving live vaccines. 1

Special Considerations for Concomitant Immunosuppression

• Concomitant use of immunosuppressants (azathioprine, 6-mercaptopurine, methotrexate) with infliximab is common and further reduces vaccine efficacy. 2, 6, 4
• Despite reduced responses, vaccination is still recommended as partial protection is better than none. 2, 7
• Timing of vaccination relative to infliximab infusion (at time of infusion versus midway between infusions) does not significantly impact response rates for influenza vaccine. 7, 8