0619: Interim Analysis of the Impact of a Recombinant Herpes Zoster Vaccine on Systemic Lupus Erythematosus: A Randomized Controlled Study on Immunogenicity, Safety and Immunosuppressor Effects

Background/Purpose: SLE patients are at increased risk of infections, including herpes zoster (HZ). Prior studies evaluating the recombinant herpes zoster vaccine (RZV) in SLE have been limited by small sample sizes and the absence of control groups. To address these gaps, we conducted a prospective, randomized controlled trial to evaluate the humoral immunogenicity, safety and impact of immunosuppressive therapies on RZV response in a large SLE cohort compared to healthy controls.

Methods: This prospective, randomized, placebo-controlled study enrolled SLE patients randomized 1:1 to receive the RZV (P1 group) or placebo (P2 group) on Day 0 (D0) and Day 42 (D42). Healthy control group (CG) received the RZV at D0 and D42. At D84, the blinding was lifted, and the placebo group (P2) received the RZV at D84 and D126. Anti-gE antibody concentrations (ELISA) were assessed before the 1st vaccine dose and 6 weeks after the 2nd dose. Disease activity was defined as new exacerbation or worsening based on SLE activity criteria: Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), Physician Global Assessment (PGA) and Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI). SLE patients (P1 and P2) were blindly analyzed for disease activity, laboratory and treatment data at D0, D42 and D84. Participants were also followed through scheduled visits and telephone contact for the first 3 months to assess adverse events.

Results: A total of 301 SLE patients and 137 controls balanced for age and sex were enrolled with 266 SLE patients completing the 3-month follow-up for this interim analysis. At D84, seroconversion was significantly lower in SLE vs. CG (89.5% vs. 99.3%, p< 0.001). SLE patients also exhibited a lower geometric mean titer (GMT) of anti-gE [7.35 (95%CI 6.35 – 8.51) vs. 11.92 (95%CI 10.66 – 13.34) mUI/mL, p=0.001] and a reduced factor increase in GMT [25.13 (95%CI 20.87 – 30.27) vs. 59.15 (95%CI 47.20 – 74.12), p< 0.001] compared to CG. The overall systemic adverse events were lower in SLE compared to CG: fever (12% vs. 21%, p=0.015) and headache (26% vs. 38, p=0.010) after the 1st dose; fever (12% vs. 22%, p=0.009) and chills (12% vs. 31%, p< 0.001) after the 2nd dose. No serious adverse events were reported. Further analysis of disease activity parameters showed no significant difference in disease flare between SLE patients receiving RZV (P1) and placebo (P2) (1.9% vs. 7.0%, p=0.104), as well as similar median of SLEDAI-2K, PGA and CLASI in both groups. Among SLE patients, male sex, lower prednisone dose, previous HZ and belimumab use were associated with higher anti-gE titers after the 2nd dose (p< 0.05). Patients receiving MMF had a reduced antibody response compared to non-users, as evaluated by GMT [6.18(95%CI 4.89 – 7.70) vs. 8.51 (95%CI 7.08 – 10.23) mUI/mL, p=0.048].

Conclusion: This large, randomized study confirms RZV safety and immunogenicity in SLE, despite a reduced response versus controls. Importantly, MMF impaired vaccine response and may require strategies to enhance protection. Conversely, we provide evidence that lower glucocorticoid doses and belimumab improves vaccination antibody titers. (ClinicalTrials NCT05879419).