Can live vaccines be given to patients on biologics?

No. Commonly used live vaccines include measles (MMR, Proquad), varicella (Varivax), oral rotavirus, Zostavax, and Flumist.

Yellow fever, BCG, oral typhoid, and adenovirus (military personnel) are live vaccines given only to high-risk groups, whereas small pox and oral polio are rarely given today.

Live vaccines are generally contraindicated in patients receiving biologic therapies, but the safety profile and specific recommendations vary depending on the type of biologic agent, degree of immunosuppression, and timing considerations. Current evidence suggests that while serious adverse events are rare, the theoretical risk of vaccine-strain infections necessitates careful evaluation.

General Contraindication Status

Live attenuated vaccines are contraindicated during treatment with biologic agents. This includes:^[1][2][3]

• TNF-alpha inhibitors (infliximab, adalimumab, etanercept, certolizumab, golimumab)
• IL-12/23 inhibitors (ustekinumab)
• IL-17 inhibitors (secukinumab, ixekizumab)
• IL-23 inhibitors (guselkumab, risankizumab)
• B-cell depleting agents (rituximab)
• T-cell co-stimulation modulators (abatacept)
• IL-6 receptor antagonists (tocilizumab)
• JAK inhibitors (tofacitinib, baricitinib, upadacitinib)

Scientific Rationale for Contraindication

The contraindication is based on several factors:^[4][2]

Theoretical Risk of Disseminated Infection:

• Live vaccines contain attenuated but viable pathogens that could cause severe disease in immunocompromised individuals
• Risk of vaccine-strain infections including disseminated varicella, measles encephalitis, or BCG-associated complications

Impaired Immune Response:

• Biologics may reduce vaccine efficacy by suppressing the immune response needed for protective immunity
• Cellular immunity, particularly important for live vaccine responses, may be compromised

Limited Safety Data:

• Most clinical trials of biologics excluded patients receiving live vaccines
• Long-term safety data in this population remains limited

Current Evidence on Safety

Despite theoretical concerns, emerging evidence suggests that serious adverse events may be less common than previously thought:

Large Observational Studies:

• A comprehensive review of 2,091 vaccinations in patients on immunosuppressants found only 23 patients (1.1%) developed vaccine-strain infections, primarily varicella^[4]
• No life-threatening complications were reported in this large cohort^[4]

Real-World Experience:

• A study of 197 patients who received live vaccines while on immunosuppressive therapy found no serious adverse events or vaccine-strain infections^[5]
• Another study of 35 IBD patients who inadvertently received live vaccines while on biologics reported no infections within three months^[6]

TNF Inhibitor-Specific Data:

• Studies of patients on TNF inhibitors who received live vaccines showed generally safe outcomes
• A Medicare study identified 663 patients vaccinated while on biologics with no cases of herpes zoster or varicella disease in the 6 weeks post-vaccination^[7]

Timing Considerations and Washout Periods

Pre-Treatment Vaccination:
Live vaccines should ideally be administered before starting biologic therapy:^[2][8]

• 4 weeks before initiation of biologics for live vaccines^[8]
• 2 weeks before for non-live vaccines^[8]

Post-Treatment Washout Periods:
After discontinuing biologics, the recommended waiting periods before live vaccine administration vary:^[2]

TNF Inhibitors:

• Etanercept: 4 weeks
• Infliximab, adalimumab: 3 months
• General recommendation: 3-5 half-lives of the medication

Other Biologics:

• Rituximab: 6-12 months (until B-cell recovery)
• Abatacept: 3 months
• Tocilizumab: 3 months

Special Populations and Exceptions

Pediatric Considerations

Infants with In-Utero Biologic Exposure:
Recent guidelines provide specific recommendations for rotavirus vaccination in infants exposed to biologics during pregnancy:^[9][10][11]

• TNF inhibitor exposure: Rotavirus vaccine can be given within the first 6 months of life
• Rituximab exposure: Delay rotavirus vaccine until after 6 months of age
• MMR and varicella vaccines: Can be safely administered at 12-15 months when maternal drug levels are negligible^[12]

Low-Dose Immunosuppression

Some guidelines allow for live vaccine administration in patients on low-dose immunosuppressive therapy:^[2]

• Low-dose corticosteroids (<20 mg/day prednisone equivalent)
• Low-dose methotrexate (<0.4 mg/kg/week or <20 mg/week)
• Sulfasalazine or hydroxychloroquine monotherapy

Current Research and Future Directions

Immunological Criteria for Safety:
Japanese research has identified potential immunological parameters for safe live vaccine administration:^[4]

• CD4 cell count ≥500/mm³
• Lymphocyte stimulation index ≥101.6
• Serum IgG ≥300 mg/dL

Vaccine-Specific Considerations:

• Herpes zoster vaccine: Some experts suggest it may be considered in select patients on mild immunosuppression^[7][12]
• MMR and varicella: Generally safer profiles compared to other live vaccines^[4]

Practical Clinical Recommendations

Before Starting Biologics:

1. Update all vaccinations including live vaccines at least 4 weeks before therapy initiation
2. Screen for vaccine-preventable diseases and provide catch-up immunizations
3. Consider additional vaccines not routinely recommended for immunocompetent individuals

During Biologic Therapy:

1. Avoid all live vaccines as standard practice
2. Use inactivated vaccines when available (e.g., inactivated influenza instead of live attenuated)
3. Consult specialists if live vaccine administration is being considered for compelling reasons

Risk-Benefit Assessment:
In exceptional circumstances where live vaccines might be considered:

1. Evaluate degree of immunosuppression
2. Consider disease activity and overall immune status
3. Assess epidemiological risk of vaccine-preventable disease
4. Involve infectious disease specialists in decision-making

Conclusion

While live vaccines remain contraindicated in patients receiving biologic therapies due to theoretical safety concerns, emerging evidence suggests that serious adverse events may be less frequent than previously anticipated. However, the current standard of care maintains this contraindication given the availability of alternative preventive strategies and the potential for serious complications in immunocompromised individuals.

The optimal approach involves comprehensive pre-treatment vaccination, use of inactivated alternatives when available, and individualized risk assessment for exceptional circumstances. As more safety data becomes available, future guidelines may provide more nuanced recommendations for specific patient populations and biologic agents.

Healthcare providers should stay current with evolving recommendations from professional societies and regulatory agencies, as this remains an active area of clinical research and guideline development.

Patients should be given a live vaccine at least 4 weeks before starting a biologic therapy.

Timing of Live Vaccination Before Initiation of Biologic Therapy

Key Recommendation:
Live, attenuated vaccines should be administered at least 4 weeks before initiating biologic or other immunosuppressive therapies to allow development of a robust immune response and to minimize the risk of vaccine-related complications.

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Rationale and Guideline Consensus

Biologic agents and other immunosuppressive treatments impair the body’s ability to mount protective responses to live vaccines and may increase the risk of disseminated infection from vaccine strains. Clinical guidelines therefore recommend:

• General Immunosuppression: Administer live vaccines ≥4 weeks before starting immunosuppressive therapy, including biologic DMARDs and high-dose corticosteroids (≥20 mg/day prednisone or equivalent for >2 weeks).
• Biologic-Specific Considerations:
  • For most biologic DMARDs (e.g., TNF inhibitors, IL-17/23 inhibitors), vaccinate ≥4 weeks prior or wait one full dosing interval before vaccination if therapy must begin sooner.
  • For B-cell–depleting agents (e.g., rituximab), ideally vaccinate ≥5 half-lives before therapy or ≥6 months prior to the next infusion, if possible, to ensure adequate humoral response and B-cell recovery.

Underlying Immunology

• Humoral Response Development:
  • Primary live-attenuated vaccines induce low-affinity IgM by ~1 week, with high-affinity IgG peaking at 4–6 weeks.
  • Interrupting therapy or delaying its start for ≥4 weeks post-vaccination optimizes antibody maturation and T-cell memory formation.

Special Scenarios

• Urgent Biologic Initiation: If delaying therapy poses unacceptable risk, consult a specialist to weigh the benefits of early biologic therapy against potential vaccine failure or adverse effects.
• Household Contacts: Ensure close contacts receive all age-appropriate vaccinations (except smallpox) to create a “cocoon” of indirect protection around immunosuppressed patients.

Ensuring a minimum 4-week interval between live vaccination and biologic therapy maximizes vaccine efficacy and safety, aligning with CDC, EULAR, and rheumatology society recommendations.

If already on a biologic agent, the patients are recommended to stop the biologic at least 3 months before receiving the live vaccine.

Others recommend that a live vaccine can be given if a patient has stopped the biologic for at least three to five times its half-life (9–15 days after ETN; 4–6 weeks after INF and ADA; 6–10 weeks after golimumab, certolizumab, tocilizumab, or abatacept; 9–15 weeks after RTX).

Vaccinations for patients with autoimmune diseases — specifically patients being treated with biologics — bring with them a variety of issues, including disease-specific, medication-related, and vaccine-associated factors, researchers suggested.

Patients with diseases such as rheumatoid arthritis and systemic lupus erythematosus are at increased risk for infections because of aberrations in their immune system and long-term treatments with conventional immunosuppressive therapies.

The concern has become even more acute with the widespread adoption of biologic therapies, as these agents can further increase patients’ susceptibility to serious infections.

And while published recommendations exist for vaccinations in patients on conventional treatments, no guidelines exist for those on biologics.

The administration of live vaccines to patients receiving biologic medications is a complex issue that requires careful consideration of individual medical conditions, the specific biologic being used, and the type of live vaccine involved. Biologic medications, often used to treat conditions like autoimmune disorders, inflammatory diseases, and cancer, can suppress the immune system to varying degrees.

Live vaccines contain weakened but live forms of viruses and bacteria, and there is a concern that these vaccines could potentially cause infections in individuals with compromised immune systems.

Summary

Here are some general points to consider while considering live vaccines be given to patients on biologics:

1. Immune Suppression: Biologic medications can suppress the immune system, which may reduce the effectiveness of live vaccines and increase the risk of infections.
2. Timing: The timing of vaccine administration relative to biologic treatment matters. In some cases, live vaccines may need to be given before starting biologic therapy or during a temporary pause in treatment.
3. Individualized Approach: Decisions about vaccinations should be made on an individual basis. The patient’s specific condition, the biologic being used, and the risk of exposure to the diseases targeted by the vaccines should all be taken into account.
4. Vaccine Types: Some live vaccines, like the measles, mumps, and rubella (MMR) vaccine, the varicella (chickenpox) vaccine, and the yellow fever vaccine, are more concerning due to the potential for causing infections in immunocompromised individuals.
5. Alternative Vaccines: In cases where live vaccines are not recommended, patients might be offered alternative vaccines that contain inactivated (killed) viruses or bacteria.
6. Consultation with Healthcare Provider: Patients on biologic medications should discuss their vaccination status and needs with their healthcare provider. The provider can guide them on when to receive vaccines, which vaccines are safe, and any necessary precautions.
7. Weighing Risks and Benefits: The decision to administer live vaccines to individuals on biologics involves weighing the potential benefits of vaccination against the risks of infections or reduced vaccine efficacy.

Ultimately, decisions about administering live vaccines to patients on biologics should be made by a healthcare provider who has a comprehensive understanding of the patient’s medical history, the specific biologic treatment, and the vaccines in question. The provider can offer personalized recommendations and guidance to ensure the best possible outcome for the patient’s health.

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