What are the recommendations for administering the shingles vaccine to patients taking Rituximab (rituximab)?

Shingles Vaccine and Rituximab

Direct Recommendation

Administer the recombinant zoster vaccine (Shingrix) at least 2-4 weeks before initiating rituximab therapy, as rituximab profoundly impairs vaccine responses for 6-9 months after treatment. 1, 2, 3 If the patient is already on rituximab, wait at least 6 months after the last dose (ideally 9-12 months when B-cell recovery is complete) before vaccinating, then delay the next rituximab dose by at least 4 weeks post-vaccination. 1, 4

Vaccine Selection: Recombinant vs Live

• Use only the recombinant zoster vaccine (RZV/Shingrix), never the live zoster vaccine (ZVL/Zostavax) in patients who will receive or are receiving rituximab. 1
• The live vaccine is absolutely contraindicated in immunocompromised patients, including those on rituximab, due to risk of vaccine-strain varicella dissemination. 1
• The recombinant vaccine has demonstrated significant T-cell responses even in patients with hematologic malignancies on anti-CD20 therapies, making it the safer and more effective choice. 1

Optimal Timing Algorithm

Scenario 1: Patient Not Yet Started on Rituximab (Optimal)

• Week 0: Administer first dose of recombinant zoster vaccine (RZV) along with other indicated vaccines (PCV13, influenza, Tdap). 2, 3
• Week 4-8: Administer second dose of RZV (required 2-6 months after first dose per manufacturer guidelines). 2, 3
• Week 8-12: Initiate rituximab therapy. 2, 3
• This timing maximizes seroconversion rates (87-91%) compared to post-rituximab vaccination (61-65%). 4

Scenario 2: Patient Already on Rituximab (Suboptimal but Necessary)

• Wait at least 6 months after last rituximab dose, ideally 9-12 months when B-cell recovery is complete. 1, 4
• Administer both doses of RZV during this window. 1
• Delay next rituximab dose by at least 4 weeks after completing the vaccine series. 1
• Patients receiving vaccines ≥9 months after rituximab cessation achieve responses comparable to healthy controls. 4

Scenario 3: Urgent Rituximab Needed (Minimum Acceptable)

• If disease activity requires urgent rituximab initiation, administer at least the first dose of RZV 2 weeks before rituximab. 2, 3
• Plan the second RZV dose for the next rituximab cycle (at least 6 months after last rituximab dose). 1

Mechanistic Rationale

• Rituximab causes profound B-cell depletion lasting 6-9 months, with full recovery typically occurring 9-12 months after therapy. 3, 4
• Humoral antibody responses to vaccines are severely hampered during this period. 1, 3
• Tetanus toxoid vaccination showed adequate responses only when given 24 weeks after rituximab, while influenza and pneumococcal vaccines given 1-7 months post-rituximab had severely reduced responses. 1
• The impairment is reversible: adequate vaccination ≥9 months after rituximab cessation restores responses comparable to healthy controls. 4

Clinical Context and Risk

• Patients with autoimmune inflammatory rheumatic diseases have significantly increased risk of herpes zoster compared to the general population. 1
• This risk is further amplified by rituximab treatment itself. 1, 5
• Case reports document VZV reactivation following rituximab treatment in AAV patients, reinforcing the need for pre-treatment vaccination. 5
• The recombinant zoster vaccine should be recommended before starting rituximab induction therapy. 5

Post-Vaccination Monitoring

• Measure VZV-specific antibody titers 4 weeks after completing the vaccine series to confirm adequate response. 2, 3
• Cell-mediated VZV-specific T-cell responses correlate more strongly with protection than humoral responses, though this testing is not routinely available. 1
• If titers are inadequate and rituximab has been discontinued for ≥9 months, consider revaccination. 4

Critical Pitfalls to Avoid

• Never administer live zoster vaccine (Zostavax) to patients on or planning rituximab therapy. 1
• Do not assume vaccine responses are adequate without checking titers, especially if vaccination occurred close to rituximab administration. 3
• Do not delay rituximab indefinitely for vaccination if disease is highly active—use the minimum acceptable timing (2 weeks pre-rituximab for first dose). 3
• Do not forget that vaccine impairment is reversible; patients can be successfully vaccinated after adequate B-cell recovery. 4

Safety Considerations

• The recombinant zoster vaccine is non-live and safe to administer to immunocompromised patients. 1
• Infusion-related reactions to rituximab occur in the majority of patients but are usually mild; severe reactions occur in ~10% and are reversible with supportive care. 6
• Prophylactic antiviral therapy for herpes zoster may be considered in high-risk patients during rituximab treatment, though this is not a substitute for vaccination. 1