A patient with no history of varicella infection or varicella vaccination is about to start the JAK inhibitor tofacitinib; which vaccine(s) should be given: only the recombinant zoster vaccine (Shingrix), only the live varicella vaccine (Varivax), or both?

Vaccination Strategy for Varicella-Naïve Patient Starting Tofacitinib

A patient with no history of varicella infection or vaccination who is about to start tofacitinib should receive only Varivax (live varicella vaccine) before initiating therapy—not Shingrix. Shingrix is contraindicated in this scenario because it prevents herpes zoster reactivation in patients who already have latent varicella-zoster virus (VZV), but this patient has never been infected with VZV and therefore has no latent virus to reactivate. 1

Clinical Rationale and Algorithm

Step 1: Confirm VZV Seronegativity

• Obtain a history of chickenpox or varicella vaccination; if uncertain or the patient was raised in a tropical/subtropical region, confirm VZV IgG seronegativity through laboratory testing. 1
• This patient's lack of both natural infection and vaccination history makes them susceptible to primary varicella infection, not herpes zoster reactivation. 1

Step 2: Administer Varivax Before Tofacitinib

• Give the 2-dose Varivax series (doses 4 weeks apart) and wait at least 4 weeks after the second dose before starting tofacitinib. 1
• Live varicella vaccination must be completed before immunosuppressive therapy because live vaccines are absolutely contraindicated once JAK inhibitor therapy begins. 1, 2
• The UK Department of Health recommends a 4-week window between live vaccination and starting immunosuppressive therapy to allow establishment of an immune response. 1

Step 3: Critical Safety Consideration

• Never administer live varicella vaccine (Varivax) after tofacitinib has been started. The FDA label for tofacitinib reports a case of disseminated vaccine-strain varicella zoster virus occurring 16 days after live-attenuated Zostavax vaccination and 2 days after starting tofacitinib 5 mg twice daily in a varicella-naïve patient. 2
• This case underscores the absolute contraindication of live vaccines in patients already receiving JAK inhibitors. 2

Step 4: Future Shingrix Administration

• Only after the patient has received Varivax and established VZV seropositivity should Shingrix be considered—but this would occur years later (age ≥50 years for standard indications, or age ≥18 years if still on JAK inhibitor therapy). 1, 3
• Shingrix prevents herpes zoster reactivation; it does not protect against primary varicella infection. 4, 5

Why Shingrix Alone Is Incorrect

• Shingrix contains only the VZV glycoprotein E antigen, not the complete virus, and is designed to boost cell-mediated immunity against reactivation of latent VZV in individuals who have already had chickenpox or vaccination. 4, 5
• A varicella-naïve patient has no latent VZV in dorsal root ganglia; therefore, Shingrix provides no protection against primary varicella infection. 4
• Guidelines explicitly state that if a patient is documented VZV-seronegative, the recommended approach is a 2-dose varicella vaccine series spaced 4 weeks apart, rather than a zoster vaccine. 3

Why Both Vaccines Together Is Incorrect

• Administering both vaccines simultaneously or sequentially before tofacitinib initiation is unnecessary and potentially harmful because:
  • Varivax alone will establish VZV immunity and prevent primary varicella infection. 1
  • Shingrix is only indicated for herpes zoster prevention in adults ≥50 years (or ≥18 years on JAK inhibitors), not for primary varicella prevention. 1, 3
  • Giving Shingrix to a varicella-naïve patient wastes resources and exposes the patient to unnecessary injection-site reactions and systemic symptoms. 3

Practical Implementation

If Urgent Tofacitinib Initiation Is Required

• If a suitable window of time cannot be identified for the full 2-dose Varivax series (e.g., severe disease requiring immediate JAK inhibitor therapy), do not vaccinate with live vaccine after starting tofacitinib. 1, 2
• Instead, advise the patient to avoid contact with people with active chickenpox or herpes zoster and to seek guidance on post-exposure prophylaxis (aciclovir for 7 days starting 7 days after exposure) if exposed. 1

If Elective Tofacitinib Start

• Administer the first Varivax dose immediately, wait 4 weeks, give the second Varivax dose, wait an additional 4 weeks, then start tofacitinib. 1
• Immunomodulators should be withheld for 4 weeks after live vaccine administration. 1

Common Pitfalls to Avoid

• Do not confuse varicella (chickenpox) vaccination with herpes zoster (shingles) vaccination—they address different clinical scenarios. 3
• Do not assume that lack of recalled chickenpox history means the patient is seronegative—88–91% of adults have VZV exposure despite lacking a recalled episode—but this patient's explicit lack of both infection and vaccination history warrants serologic confirmation or presumptive vaccination. 3
• Do not delay tofacitinib indefinitely if vaccination cannot be completed; in such cases, prioritize disease control and implement post-exposure prophylaxis strategies. 1
• Do not use Zostavax (live zoster vaccine) in any patient about to start or already on tofacitinib—only Shingrix is appropriate for zoster prevention in immunosuppressed patients, and only after VZV immunity is established. 1, 2