When should Shingrix (recombinant zoster vaccine) be administered in relation to starting tofacitinib (Xeljanz) therapy?

Timing of Shingrix Administration Before Starting Tofacitinib

Shingrix should ideally be administered and completed (both doses) before initiating tofacitinib, but if this is not feasible, give at least the first dose before starting therapy. 1

Optimal Vaccination Strategy

Pre-Treatment Vaccination (Preferred Approach)

• Complete the full 2-dose Shingrix series before starting tofacitinib whenever possible. 1
• The two doses should be separated by 2-6 months under standard circumstances. 2
• This approach maximizes immune response while the patient is not yet immunosuppressed. 1

Minimum Acceptable Timing

• If urgent tofacitinib initiation is required, administer at least the first Shingrix dose before starting therapy. 1
• The second dose can be completed after tofacitinib has been started, though immune response may be somewhat reduced. 1
• For immunocompromised patients already on therapy, a shortened interval of 1-2 months between doses is acceptable. 1

Clinical Rationale

Risk of Herpes Zoster with Tofacitinib

• Tofacitinib significantly increases herpes zoster risk through JAK1/2 inhibition, which impairs interferon-γ signaling and cellular cytotoxicity against viral pathogens. 1
• Patients with autoimmune inflammatory rheumatic diseases already have elevated baseline herpes zoster risk, which is further amplified by JAK inhibitor therapy. 1
• Real-world data shows herpes zoster rates <3% in patients on JAK inhibitors, but this risk is higher than with other immunosuppressive therapies. 1

Vaccine Efficacy Considerations

• Shingrix is a non-live recombinant vaccine, making it safe to administer even after tofacitinib has been started, unlike the older live-attenuated Zostavax. 1, 2
• Real-world effectiveness demonstrates 70.1% protection with 2 doses and 56.9% with 1 dose, emphasizing the importance of completing both doses. 3
• The vaccine maintains efficacy for at least 8 years with minimal waning (>83.3% efficacy). 2

Evidence from Tofacitinib-Specific Studies

Safety Data

• A phase II trial demonstrated that patients who received live zoster vaccine 2-3 weeks before starting tofacitinib had adequate immune responses, though one patient without pre-existing VZV immunity developed vaccine dissemination. 4
• This study supports the safety of vaccination shortly before tofacitinib initiation, though Shingrix (non-live) is now preferred over live vaccine. 1, 4

Clinical Experience

• Case reports document severe herpes zoster complications (including meningitis) in patients on tofacitinib who were not vaccinated, with Shingrix administered 2 years post-event for secondary prevention. 5
• Breakthrough herpes zoster can occur even after Shingrix vaccination, though this is uncommon and typically less severe. 6

Practical Implementation Algorithm

Scenario 1: Elective Tofacitinib Start

1. Administer first Shingrix dose immediately
2. Wait 2-6 months and give second dose
3. Start tofacitinib after completing vaccination series
4. This approach is supported by EULAR and AAD/NPF guidelines. 1

Scenario 2: Urgent Tofacitinib Needed

1. Administer first Shingrix dose
2. Start tofacitinib 2-3 weeks after first vaccine dose (allows initial immune response)
3. Complete second Shingrix dose 1-2 months later (shortened interval acceptable for immunocompromised)
4. This balances disease control with infection prevention. 1, 4

Scenario 3: Patient Already on Tofacitinib

1. Administer Shingrix immediately—do not delay vaccination
2. Give second dose 1-2 months after first dose (shortened interval for immunocompromised patients)
3. Expect potentially reduced but still clinically meaningful immune response
4. Non-live vaccine makes this safe even during active immunosuppression. 1

Important Caveats and Pitfalls

Contraindications to Avoid

• Never use live-attenuated Zostavax in patients on or about to start tofacitinib—only Shingrix is appropriate. 1, 7
• Live vaccines should be avoided in patients already taking tofacitinib. 1

Monitoring Considerations

• Baseline screening should include assessment of prior varicella exposure/immunity, though this does not preclude Shingrix administration. 1
• Patients should be counseled that breakthrough herpes zoster remains possible despite vaccination, though risk is substantially reduced. 3, 6

Special Populations

• For patients with cardiovascular risk factors, elderly patients, or those with prior thrombotic events, the decision to use tofacitinib requires careful risk-benefit assessment, but this does not change Shingrix timing recommendations. 7
• Vaccination is recommended for all patients ≥18 years starting tofacitinib, not just those ≥50 years (the general population recommendation). 1

Baseline Screening Requirements

Before initiating tofacitinib, complete the following in addition to Shingrix vaccination: 7

• Tuberculosis screening (interferon-gamma release assay or tuberculin skin test)
• Hepatitis B and C serologies
• Complete blood count with differential
• Liver and renal function tests
• Lipid panel