Immunogenicity, Safety, and Determinants of Recombinant Zoster Vaccine Response in Idiopathic Inflammatory Myopathies: A Phase 4 Randomized Trial.

Abstract

To evaluate the immunogenicity and safety of the recombinant zoster vaccine (RZV) in immunosuppressed patients with idiopathic inflammatory myopathies (IIM), with particular focus on its impact on disease activity. This sub-analysis of a randomized, double-blind, placebo-controlled study included 70 immunocompromised adult IIM patients(2017 ACR/EULAR criteria) and 280 healthy controls (CG), who received two RZV doses. Seroconversion was defined as a ≥4-fold increase in anti-gE antibodies. Geometric mean titers(GMT) and factor increase (FI) were assessed and multivariable regression analyses were performed to identify factors associated with seroconversion. Patients were randomized 1:1 to receive RZV or placebo during the blinded phase, and disease activity was evaluated using validated instruments: analogue visual scale(VAS), Myositis Disease Activity Assessment Visual Analogue(MYOACT), Manual Muscle Test-8(MMT-8), Health Assessment Questionnaire(HAQ), and Modified Medical Research Council(mMRC) dyspnea scale and serum muscle enzymes). IIM patients were younger (53 vs. 55 years, p=0.005) and had a higher prevalence of previous herpes zoster (36.7% vs. 13.3%, p<0.001) than CG. Seroconversion rates were lower in IIM compared with CG (83.3% vs. 99.3%, p<0.001), with reduced post-vaccination GMT (6.4 vs. 11.8 mIU/mL, p=0.001) and FI-GMT (21.8 vs. 53.0, p=0.001). Mycophenolate mofetil use, higher baseline cutaneous activity, and higher baseline GMT were independently associated with reduced seroconversion (p<0.05). Adverse events, mostly mild, were reported by 35/70(50.0%) of IIM patients and by 204/280(72.8%) of CG (p<0.001). No differences in activity scores were observed between vaccine and placebo groups (p>0.05). RZV was safe and induced seroconversion in most immunosuppressed IIM patients, without evidence of vaccine-related disease activation. Attenuated antibody responses, particularly in patients receiving mycophenolate mofetil or with active cutaneous disease, support individualized vaccination strategies to optimize protection in this high-risk population(ClinicalTrials.gov NCT05879419).