Rheumatology Division, University of Sao Paulo Sao Paulo, São Paulo, Brazil
Disclosure(s): GlaxoSmithKlein(GSK): Grant/Research Support (Ongoing)
Background/Purpose: Patients with autoimmune rheumatic diseases (ARDs) are at increased risk for herpes zoster (HZ), especially those treated with B-cell depleting agents. Although the recombinant zoster vaccine (RZV) has demonstrated high efficacy in healthy individuals, its immunogenicity in rituximab (RTX)-treated ARD patients remains poorly defined. This study aims to assess humoral immunogenicity to the RZV in ARD patients treated with RTX (ARD-RTX group), compared to both healthy control group (CG) and immunosuppressed ARD patients not exposed to RTX (ARD-NO RTX). Secondarily, to evaluate the influence of demographic variables, disease, and concomitant immunosuppressive drugs on RZV immune response in RTX-treated ARD patients. Methods: This prospective controlled phase 4 study included adult ARD patients who had received at least one cycle of RTX 22–28 weeks prior to enrollment (ARD-RTX group). Two comparator groups were included: a CG of non-immunosuppressed individuals (1:3 ratio) and ARD-NO RTX group (1:3 ratio). All participants received two intramuscular doses of RZV six weeks apart. Anti-glycoprotein E (anti-gE) antibody levels were measured before the first dose and six weeks after the second dose. Anti-gE geometric mean titers (GMTs) were calculated and humoral response/seroconversion (SC) was defined as a 4-fold increase in titers. Adverse events were assessed. Results: 76 patients ARD-RTX and 228 CG subjects were enrolled. The ARD-RTX included rheumatoid arthritis (36%), systemic lupus erythematosus (26%), Sjögren disease (13%), systemic sclerosis (11%), systemic autoimmune myopathy (17%), and ANCA-associated vasculitis (4%). Seventy-two ARD-RTX patients were compared to 216 ARD-NO RTX group with similar mean age, sex distribution and diagnoses (p > 0.05). Glucocorticoids use was higher in ARD-RTX (50% vs. 29.2%, p=0.001), whereas ARD-NO RTX used more leflunomide, iTNF, tocilizumab and belimumab (p < 0.05). Baseline GMTs were comparable between the three groups (p=0.487). Following full vaccination, ARD-RTX group had lower GMT compared to ARD-NO RTX group and CG [2.77 (95%CI 1.87–4.1) vs. 6.1 (95%CI 5.0–7.44) vs. 12.96 (95%CI 11.87–14.15) mUI/mL, p < 0.001] (Figure 1). Similarly, factor increase in GMT was reduced in ARD-RTX compared to ARD-NO RTX and CG [12.3 (95%CI 7.6-19.8) vs. 31.4 (95%CI 24.6-40.0) vs. 64.6 (95%CI 54.3-76.8), p< 0.001]. ARD-RTX patients also demonstrated a lower SC compared to ARD-NO RTX and CG group (66% vs. 85.6% vs. 99%, p< 0.001). There was no association of SC in ARD-RTX with age, ARD diagnosis, glucocorticoid, or immunosuppressive therapies (p >0.05). Regarding safety, no severe adverse events were reported. Local reactions (60.5% vs. 84.6%, p< 0.0001) and systemic reactions (39.5% vs. 63.2%, p< 0.0001) following first vaccine dose were significantly lower in ARD-RTX group compared to CG. Conclusion: RTX significantly impairs humoral response to RZV in ARDs, independent of age, diagnosis, or concomitant immunosuppression. These findings highlight a possible vulnerability in vaccine protection and support the consideration of RZV before RTX use to optimize immune response (ClinicalTrials NCT05879419).
