0206: Prospective Controlled Study of Humoral Response to Recombinant Zoster Vaccine in Cyclophosphamide-Treated Autoimmune Rheumatic Disease Patients: No Additional Impairment Compared to Other Immunosuppressive Therapies

Background/Purpose: Recombinant zoster vaccine (RZV), represents a major advancement in the prevention of herpes zoster in autoimmune rheumatic diseases (ARD) patients. However, RVZ efficacy depends on strong cellular and humoral immune response. Intravenous cyclophosphamide (IVCYC) is a potent immunosuppressive agent known to impair both arms of the immune system. Therefore, it is important to evaluate the impact of IVCYC on RVZ humoral immunogenicity in ARD patients, and to explore factors that may influence vaccine response.

Methods: This was a subgroup analysis of ARD patients (≥18 years) currently receiving IVCYC (ARD-IVCYC) enrolled in a phase 4 randomized placebo-controlled prospective study. Healthy immunocompetent adults ≥50 years (CG) and patients not treated with IVCYC (ARD-No IVCYC) were included as comparison groups (1:4 ratio). ARD-IVCYC patients were randomized in two groups: P1 (vaccine) and P2 (placebo). CG and P1 received RZV (D0 and D42); P2 initially received placebo, followed by RZV (D84 and D126). Humoral response to RZV was defined as anti-gE concentration (ELISA) ≥4-fold the pre-vaccination level and evaluated at baseline and 6 weeks after second dose. GMT was also calculated. Disease activity was assessed using ARD-specific activity indices. Adverse events (AEs) were recorded.

Results: 42 ARD-IVCYC, 168 CG and 168 ARD-no IVCYC individuals were included. Among ARD-IVCYC, 34% were treated according to the EuroLupus protocol, 54% National Institutes of Health (NIH) regimen, and 10% followed the CYCLOPS protocol for vasculitis. The median cumulative dose of IVCYC was 3 g (3-4.5). Groups were comparable for sex (p< 0.05), although ARD-IVCYC and ARD-No IVCYC were younger than CG (40 vs. 40 vs. 52 years, p< 0.001). ARD diagnoses were similar between ARD-IVCYC and ARD-No IVCYC groups (p >0.05), except for a higher frequency of vasculitis in the former (10.8% vs. 0%, p< 0.001). Regarding immunogenicity, ARD-IVCYC and ARD-No IVCYC had comparable humoral response but lower than CG (91.9% vs. 91.1% vs. 99.4%, p < 0.002). Post-immunization GMT were alike in ARD-IVCYC and ARD-No IVCYC groups but both significantly lower than CG [7.53 (95% CI 5.09–11.15) vs. 6.64 (95% CI 5.58-7.91) vs. 13.2 (95% CI 12.0–14.58) mUI/mL, p < 0.001]. Among ARD-IVCYC patients, those with post-RZV anti-gE titers < 7.53 mUI/mL more frequently used mycophenolate mofetil (33% vs 5.3%, p=0.042), with no differences in age, diagnosis, glucocorticoid, or other therapies compared to those with titer ≥7.53 mUI/mL (p >0.05). Flare rates were similar between vaccine (P1) and placebo (P2) groups (25% vs. 22.7%, p=0.592). Local and systemic AEs were less frequently reported by ARD-IVCYC compared to CG after both RZV doses (p< 0.05). No severe AEs were reported.

Conclusion: Our findings demonstrate that IVCYC is safe and, unexpectedly, does not exert a more detrimental effect on the humoral response to RZV than other immunosuppressive agents used in ARD, particularly MMF. Although the response rate was high, the lower immunogenicity compared to controls, despite the younger age, reinforces the need for close surveillance for HZ risk. (ClinicalTrials NCT05879419).