RECOMBINANT HERPES ZOSTER VACCINE (RZV) IN A LARGE COHORT OF AUTOIMMUNE RHEUMATIC DISEASES PATIENTS: A PROSPECTIVE DOUBLE-BLIND RANDOMIZED PLACEBO-CONTROLLED PHASE 4 STUDY

PT005 / #801 Topic: AS17 - Miscellaneous POSTER TOUR 01: CLINICAL OUTCOMES IN SLE 22-05-2025 10:00 AM - 10:40 AM Background/Purpose Patients with autoimmune rheumatic diseases (ARDs) are at high risk of herpes zoster (HZ) and the new recombinant vaccine against HZ (RZV) offers safety improvements. This study evaluates disease safety, overall safety and humoral immunogenicity of RZV in ARD patients compared to nonvaccinated ARDs and nonimmunosuppressed control group (CG). Methods This prospective double-blind randomized placebo-controlled phase 4 study evaluated ARD patients at high risk of HZ. Participants aged >18 years were randomized into 2 groups: P1 (vaccine) and P2 (placebo), with nonimmunosuppressed individuals serving as CG. Both P1 and CG received 2 intramuscular doses of RZV administered 6 weeks apart (D0 - V1 and D42 - V2), while P2 received placebo. Disease activity was evaluated using specific scores and adverse events (AEs) were assessed through a standardized questionnaire. Blood samples were collected prior to the 1st dose (V1) and 6 weeks following the 2nd dose (V3) with humoral immunogenicity measured via anti-gE antibody serum concentrations (ELISA). Results A total 1,012 ARD patients (P1:529 and P2:483) and 393 CG completed the study. ARDs included 9 different chronic conditions, mainly rheumatoid arthritis (n = 290) and systemic lupus erythematosus (n = 302). At baseline, treatments included prednisone (39%), hydroxychloroquine (31%), sulfasalazine (6%), immunosuppressive drugs (79%) [mycophenolate mofetil (24%), methotrexate (23%), leflunomide (20%), azathioprine (18%) and cyclosporine (2%), tacrolimus (2%) and cyclophosphamide (3%)], biologic therapy (44%) [TNFi (17%), tocilizumab (8%), rituximab (7%), belimumab (6%), secukinumab (5%) and anifrolumab (1%)] and JAK inhibitors (4%). P1(vaccine) and P2 (placebo) groups were balanced for age [50 (IQR 39.8 - 61) vs 51 (IQR 40 - 61.8) years, p = 0.543], female sex (77% vs 80%, p = 0.314), ARD diagnoses and therapies (p > 0.05), except for lower frequency of mycophenolate mofetil (MMF) in P1 (p = 0.047). The primary endpoint showed comparable flare frequencies in P1 and P2 at V2 (4.1% vs 6.2%, p = 0.142) and V3 (10.2% vs 11.6%, p = 0.506). Secondary endpoints revealed no moderate/severe AEs, but AEs were less frequent in P1 (78% vs 90%, p < 0.0001), including both local (72% vs 85% p < 0.0001) and systemic reactions (50% vs 62%, p = 0.001), mainly headache (24% vs 33%, p=0.005), fatigue (16% vs 24%, p = 0.008), drowsiness (16% vs 23%, p = 0.015), myalgia (16% vs 21%, p = 0.034), chills (15% vs 21%, p = 0.012) and fever (11% vs 19%, p=0.002) after 1st RZV dose. Although humoral response was adequate, it was lower in P1 compared to CG (92% vs 99%, p < 0.0001). Baseline GMT was similar (p = 0.674), but the GMT increase after 2 doses was lower in P1 than in CG [35.09 (95%CI 30.49-40.4) vs 64.52 (95%CI 55.97-74.38); p < 0.001]. Multivariate analysis identified rituximab [OR 0.152 (95%CI 0.059-0.393), p < 0.0001] and MMF [OR 0.0460 (95%CI 0.224-0.946), p = 0.035] as major deleterious factors for reduced vaccine response. No HZ case were confirmed by RT-PCR up to week 12. Conclusions RVZ demonstrated a strong disease safety profile and adequate short-term immunogenicity in highly immunosuppressed ARD patients, including those with active diseases, with no severe adverse events and no significant impact on disease activity. Our findings highlight MMF and rituximab as key factors impairing vaccine immunogenicity, suggesting that a booster dose may be beneficial for patients on these therapies.