Immunogenicity and safety of recombinant zoster vaccine in Japanese patients with RA receiving upadacitinib: the end Zoster-J study

Patients with rheumatoid arthritis (RA) treated with Janus kinase (JAK) inhibitors are at increased risk of herpes zoster (HZ). Although the adjuvanted recombinant zoster vaccine (RZV) is recommended, its immunogenicity and safety under JAK inhibitor therapy remain incompletely characterized. We evaluated humoral and cellular immune responses and safety of RZV in Japanese patients with RA receiving methotrexate (MTX), upadacitinib (UPA), or their combination. This single-center, prospective, open-label, observational study enrolled 69 patients with RA aged ≥ 50 years (23 per group) receiving stable MTX (6–12 mg/week; Group 1), UPA (15 mg/day; Group 2), or combination therapy (Group 3). All participants received two doses of RZV 8 weeks apart. The primary endpoint was the proportion of patients achieving a ≥ 4-fold increase in anti-glycoprotein E (gE) antibody levels at week 12. Secondary endpoints included gE-specific CD4 + T-cell responses, varicella-zoster virus (VZV)–specific antibodies, RA disease activity, and adverse events. After the first RZV dose, anti-gE antibody responses were numerically lower in patients receiving UPA ( P = 0.083). However, response rates increased after completion of the two-dose regimen in all three groups, and the differences observed after the first dose became less apparent (81.8, 71.4, and 68.2%, respectively; P = 0.562). Similar catch-up patterns were observed for gE-specific CD4 + T-cell and VZV-specific antibody responses. In an exploratory analysis, patients with a prior history of HZ (23.2%) exhibited higher humoral responses after vaccination, whereas no clear differences in cellular responses were observed. RA disease activity remained stable in all treatment groups throughout the study. RA flares occurred in 26.1% of patients in the MTX group and 8.7% in the UPA and the MTX + UPA group. Adverse events occurred in 52.2% of patients, with no major safety signals. RZV elicited robust humoral and cellular immune responses in patients with RA receiving UPA, MTX, or their combination, without clinically meaningful worsening of disease activity. These findings support current recommendations for RZV vaccination in patients with RA. Trial registration: This study was registered with the Japan Registry of Clinical Trials (jRCTs051220105) on 14 October 2022.