2527: Safety Profile and Impaired Humoral Response to the Recombinant Herpes Zoster Vaccine in Behçet’s Syndrome Patients under Immunosuppression: a Prospective, Randomized, Placebo-Controlled Trial

Background/Purpose: Although rare, new-onset Behçet’s syndrome (BS) and disease flares have been reported following vaccination. In this context, the recommendation of the Recombinant Herpes Zoster Vaccine (RVZ) for immunosuppressed patients raises important questions regarding its safety and immunogenicity in BS under immunosuppressive (IS) therapy.

Methods: This prospective, randomized, placebo-controlled, single-center trial included 46 BS patients under IS, randomized 1:1 into: P1 (RZV) and P2 (placebo) groups. A healthy control group (CG) of 138 subjects was included at a 3:1 ratio and age-paired to BS patients (±3 years for patients ≥50 years; 50–55 years for BS patients < 50 years). P1 and CG received two intramuscular RZV doses on D0 and D42, while P2 received placebo. At D84, blinding was opened and P2 received RZV following the same schedule. Blood samples were collected at baseline and 6-weeks after the second dose. Humoral immunogenicity was assessed by ELISA for anti-gE antibodies, with a positive response defined as a ≥4-fold increase above the baseline level. Geometric mean titers (GMTs) and factor increase (FI) were calculated. Local and systemic side-effects were recorded in a diary after RZV for both groups. BS patients recorded new oral/genital ulcers and disease activity was assessed at each visit with the Behçet's Disease Current Activity Form (BDCAF).

Results: BS patients were younger than controls [41(18–62) vs. 52(50–63)years, p=0.001], with 82.6% aged< 50 years vs. 100% of controls aged≥50 years (p=0.001).Percentage of female gender was lower in BS (39.1% vs. 65%;p=0.002).BS patients were using: azathioprine (54%), prednisone (37%), tumor necrosis factor inhibitors (30%), mycophenolate mofetil (22%), colchicine (13%), methotrexate (11%), tocilizumab (4%), cyclosporine (4%). Seroconversion was achieved by all BS patients (100%) and 99.3% of CG (p >0.999). A significant increase of GMT from baseline was observed in BS [0.12(0.08-0.18) vs. 7.96(5.76-11.0), p< 0.001) and in CG [0.25(0.20-0.30) vs. 13.32(11.98-14.82), p< 0.001]. The increase in GMT of BS was lower than CG (7.96 vs. 13.32, p=0.02). FI in GMT was similar in BS and CG [66.3(41.0-107.2) vs. 53.8(43.3-66.8), p=0.316]. Demographics and current therapy (including biologics and IS) did not influence antibody titers (p >0.05). Higher local (92% vs. 80.4%, p=0.028) and systemic (78% vs. 60.8%, p=0.0147) reactions were observed in CG compared to BS. Regarding disease safety, no significant differences in the percentage of new oral (p=0.622) and genital (p=0.608) ulcers, or in BDCAF scores (p=0.787) were observed.

Conclusion: Our study is the first to demonstrate that RVZ appears safe in immunosuppressed BS patients, without evidence of flares using standardized measures. Despite the universal vaccine response in younger BS, antibody titers were lower than in older healthy controls, who would normally predict a weaker response. Further studies are necessary to determine whether the lower antibody levels will compromise long-term protection. (ClinicalTrials NCT05879419).