Disease Safety, Immunogenicity, and Efficacy of Recombinant Herpes Zoster Vaccine (RZV or Shingrix) in Autoimmune Rheumatic Diseases: Launching a Randomized Phase 4 Study.

Abstract

Background: Patients with autoimmune rheumatic diseases (ARDs) are at an increased risk for herpes zoster (HZ). Vaccination is recommended for this population.

Objective: The aim of this study was to evaluate the safety of vaccination with the recombinant zoster vaccine (Shingrix) in ARD patients, humoral immunogenicity (HI), cellular immunogenicity (CI), and the incidence of HZ.

Methods: This randomized, double-blind, placebo-controlled phase 4 study involves 1180 ARD patients and a control group (CG) of 393 balanced healthy individuals, aged ≥50 years. ARD patients will be randomly assigned in a blinded manner (1:1 ratio) to 2 groups: vaccine or placebo (on days 0 and 42), administered intramuscularly. Outcomes will be assessed at baseline, 6 weeks, and 12 weeks after vaccination, including disease activity (using specific disease activity scores), HI, and CI. Adverse events will be assessed using a standardized questionnaire after each vaccine dose. Incident HZ cases will be monitored throughout the study. One year following the second dose, the persistence of HI and CI will be evaluated in both ARD patients and CG. HI and CI will be assessed using serum concentrations of anti-gE antibodies and the frequencies of gE-specific CD4+ T cells, respectively. Comparisons of anti-gE titers between ARD patients and CG at different time points will be analyzed using 2-way repeated-measures analysis of variance. Multiple regression analysis will be conducted, with a positive immune response as the dependent variable, and variables with p < 0.2 from univariate analysis as independent variables.

Conclusions: This large trial addresses a critical gap by examining disease safety, efficacy, adverse effects, and immunogenicity, considering the impact of diverse therapies following recombinant zoster vaccine administration in ARD patients.