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

OBJECTIVE: 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. METHODS: This subanalysis of a randomized, double-blind, placebo-controlled study included 70 immunocompromised adult patients with IIM (2017 ACR/EULAR criteria) and 280 healthy controls (control group [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 (visual analog scale, the Myositis Disease Activity Assessment Visual Analog Scale, Manual Muscle Test-8 (MMT-8), Health Assessment Questionnaire, and the modified Medical Research Council dyspnea scale and serum muscle enzymes. RESULTS: Patients with IIM 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 of 70 (50.0%) patients with IIM and by 204 of 280 (72.8%) CG (P < 0.001). No differences in activity scores were observed between vaccine and placebo groups (P > 0.05). CONCLUSION: RZV was safe and induced seroconversion in most immunosuppressed patients with IIM, 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).