Effectiveness and Safety of Recombinant Zoster Vaccine in Rheumatic Diseases: Real-World Evidence from a Single-Centre Italian Cohort

Abstract

Background: Patients with rheumatic diseases (RMDs) are at increased risk of herpes zoster (HZ), particularly when receiving immunosuppressive treatment. While recombinant zoster vaccine (RZV) has shown high effectiveness in the general population, evidence in rheumatologic patients remain limited due to their exclusion from pivotal trials.

Objectives: To evaluate the effectiveness of RZV and to collect additional safety data in a heterogeneous cohort of rheumatologic patients, compared with a control cohort from the general population.

Methods: We conducted a retrospective study including 179 adults who received two intramuscular doses of RZV between January 2021 and June 2025. The cohort included 114 patients with RMDs and 65 individuals from the general population. Effectiveness was defined as the ability to prevent HZ reactivation while safety concerns were recorded as any adverse event temporally associated with the vaccination.

Results: We observed a statistically significant reduction in terms of VZV relapses following vaccination (p < 0.001). Among patients diagnosed with RMDs, only one case of HZ recurrence was observed 14 weeks after vaccination, with no significant difference compared to general care patients. One patient experienced a disease flare requiring glucocorticosteroids. RZV demonstrated a favourable safety profile, with minor adverse events (fever, injection-site reactions, headache and myalgia) reported in 17.5% of patients after the first dose and 21.5% after the second. No significant association was observed between adverse events and advanced immunosuppressive therapy.

Conclusions: RZV displayed an effective and reassuring safety profile in a heterogeneous cohort of patients affected by RMDs, irrespective of the diagnosis and the ongoing therapy. This supports the broader use of RZV as a safe and valuable preventive strategy in patients with RMDs.

Keywords: RZV; Shingrix; herpes zoster; immunosuppressive therapy; systemic autoimmune diseases; vaccines.

Figure 1

Diagnosis distribution in the rheumatologic subgroup. List of abbreviations: ASyS Antisynthetase syndrome, BD Behçet disease, DM Dermatomyositis, GCA Giant cell arteritis, GPA Granulomatosis with polyangiitis, MCTD Mixed connective tissue disease, MPA Microscopic polyangiitis, PM Polymyositis, PsA Psoriatic arthritis, RA Rheumatoid arthritis, SpA Spondyloarthritis, SS Sjögren syndrome, SSc Systemic sclerosis, SLE Systemic Lupus Erythematosus, TAK Takayasu arteritis.