Shingrix Vaccination in a 51-Year-Old Woman on Rinvoq and Leflunomide
Yes, you should give Shingrix (recombinant zoster vaccine) to this patient—it is the only appropriate shingles vaccine for someone on Rinvoq (upadacitinib) and leflunomide, and it is both safe and recommended for immunocompromised individuals. 1, 2, 3
Vaccine Selection: Shingrix Only
Shingrix is the only acceptable option for patients on JAK inhibitors like Rinvoq—the live-attenuated vaccine (Zostavax) is absolutely contraindicated due to the theoretical risk of disseminated vaccine-strain infection in immunocompromised patients 1, 2, 4.
Shingrix is a non-live recombinant vaccine containing only varicella-zoster virus glycoprotein E with AS01B adjuvant, making it safe for immunosuppressed individuals 2, 3.
The FDA explicitly states that Rinvoq's prescribing information recommends avoiding live vaccines but supports prophylactic herpes zoster vaccination prior to or during therapy 4.
Why This Patient Needs Vaccination
JAK inhibitors like Rinvoq significantly increase herpes zoster risk through JAK1/2 inhibition, which impairs interferon-γ signaling and cellular immunity 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 5, 1.
The combination of Rinvoq plus leflunomide (both immunosuppressive agents) places this patient at particularly high risk for VZV reactivation 5, 6.
Dosing Schedule and Timing
Administer the standard 2-dose series: first dose immediately, second dose 2-6 months later (minimum interval 4 weeks) 7, 1, 3.
For immunocompromised adults, a shortened schedule with the second dose at 1-2 months is acceptable if earlier protection is desired 7, 1.
Do not delay vaccination—while ideally both doses would be given before starting Rinvoq, this patient is already on therapy, so proceed without interruption of upadacitinib 1.
Do not hold Rinvoq around vaccination time—continue upadacitinib without modification 1.
Consider holding leflunomide for 2 weeks after each vaccine dose to optimize immune response, similar to recommendations for methotrexate in patients on JAK inhibitors 1.
Expected Immune Response
Immune responses will be reduced compared to healthy individuals, but vaccination still provides clinically meaningful protection 2, 8, 9.
Recent data shows that patients on upadacitinib (selective JAK1 inhibitor) achieve better immune responses than those on non-selective JAK inhibitors: 83% seroconversion rate, 39% CD4 T-cell response, and 39% CD8 T-cell response 8.
This is superior to non-selective JAK inhibitors like baricitinib (64% seroconversion, 0% CD4, 7% CD8) but still lower than anti-TNF/methotrexate-treated patients (91% seroconversion, 67% CD4, 41% CD8) 8.
Meta-analysis demonstrates that RZV reduces herpes zoster incidence by 81% in immunocompromised individuals overall (RR: 0.19,95% CI: 0.09-0.44) 9.
Safety Profile
Shingrix is safe in immunocompromised patients with no increased risk of serious adverse events compared to placebo 2, 9.
Common side effects include injection-site reactions (pain, redness, swelling) in 9.5% and systemic symptoms (fatigue, myalgia, headache) in 11.4%, typically resolving within 4 days 7, 2.
No vaccination-related serious adverse events or cases of vaccine-strain VZV infection have been reported in immunosuppressed populations 5, 2.
Studies specifically in patients with autoimmune inflammatory rheumatic diseases showed vaccine efficacy of 90.5% with similar rates of serious adverse events between RZV and placebo groups 5.
Important Caveats
Breakthrough herpes zoster can still occur despite vaccination—one case report documented shingles in a patient on tofacitinib (another JAK inhibitor) despite completing the full Shingrix series 10.
However, vaccinated individuals who develop breakthrough shingles generally experience less severe disease and lower rates of post-herpetic neuralgia 7.
Factors associated with reduced vaccine response include cumulative glucocorticoid dose, longer JAK inhibitor exposure, and history of ≥2 prior DMARDs 8.
If this patient previously received Zostavax, she should still receive the full 2-dose Shingrix series (at least 2 months after the last Zostavax dose) 5, 7, 1.
Clinical Algorithm
- Verify vaccine type: Confirm Shingrix (RZV), not Zostavax (ZVL) 1.
- Administer first dose immediately without holding Rinvoq 1.
- Consider holding leflunomide for 2 weeks after the first dose to optimize response 1.
- Schedule second dose at 2-6 months (or 1-2 months for earlier protection) 7, 1, 3.
- Repeat leflunomide hold for 2 weeks after the second dose 1.
- Continue Rinvoq throughout without interruption 1.
- Counsel patient about expected injection-site reactions and systemic symptoms, and the possibility of breakthrough infection despite vaccination 7, 10.