A recent study exploring the safety of herpes zoster vaccine (HZ) in patients with rheumatoid arthritis (RA) showed vaccine safety in all patients, with the exception of one patient who did not have pre-existing varicella-zoster virus (VZV) immunity.1
The study, published in Arthritis & Rheumatology, examined the safety and immunogenicity of live zoster vaccination (LZV) in a group of patients with RA before tofacitinib therapy initiation.
The risk of herpes zoster is higher in patients with RA than in the general population, and vaccination is recommended in patients age ≥50 before starting biologics or tofacitinib, an oral Janus kinase (JAK) inhibitor for the treatment of RA.
For this phase 2, 14-week randomized double-blind placebo-controlled study (ClinicalTrials.gov identifier: NCT02147587), 112 patients with active RA on stable background methotrexate were randomly assigned to receive tofacitinib (n=55) or placebo (n=57).
Patients received LZV and started a tofacitinib regimen (5 mg twice daily) or placebo 2 to 3 weeks after vaccination. Researchers measured VZV-specific humoral- and cell-mediated responses (with immunoglobulin G [IgG] and T cell enumeration, respectively) at baseline and 2, 6, and 14 weeks post-vaccination.
Geometric mean fold rise (GMFR) in VZV-specific IgG levels was the study’s primary end point, and T cells (spot-forming cells/106 peripheral blood mononuclear cells) at 6 weeks post-vaccination was an additional end point.
Results showed that 6 weeks after getting vaccinated, VZV-specific IgG GMFR was 2.11 (1.87-2.37) for tofacitinib and 1.74 (1.55-1.95) for placebo. VZV-specific T-cell GMFR increased in a similar fashion for tofactinib (1.50; 80% CI, 1.31-1.70) and placebo (1.29; 80% CI, 1.14-1.46).
Adverse events occurred in 3 patients (5.5 %) in the tofacitinib group. One patient lacking VZV immunity developed cutaneous vaccine dissemination 2 days after starting tofacitinib (16 days post-vaccination). This situation resolved after stopping tofacitinib and receiving antiviral therapy.
The investigators concluded that starting tofacitnib does not hinder the immunogenicity of the live zoster vaccine, and that study patients were able to launch humoral and cell-mediated responses similar to those seen in other studies of healthy patients who did not have RA.
In terms of safety, there was one event of disseminated shingles vaccine (Oka) virus in a patient without prior immunity, which suggests that patients must be screened for prior immunity (by getting a history of chicken pox or testing with commercially available VZV-serology) before receiving this vaccine, or that there should be a longer gap — 4 weeks — between vaccination and beginning tofacitinib.
“Further research is necessary to understand the risk of this complication, as well as the long-term effectiveness of this vaccine to prevent HZ in this high-risk population,” the researchers noted.
Winthrop KL, Wouters A, Choy E, et al. The safety and immunogenicity of live zoster vaccination in rheumatoid arthritis [published online August 28, 2017]. Arthritis & Dermatology. doi:10. 1002/art.40187