Background/Purpose: Systemic sclerosis (SSc) patients are at higher risk of herpes zoster (HZ) due to underlying immune dysregulation and immunosuppressive therapies. Vaccination is a key strategy for preventing HZ. Although the recombinant zoster vaccine (RZV/Shingrix®) is approved for immunocompromised individuals, its immunogenicity, safety, and impact on disease activity (DA) have not been specifically evaluated in SSc patients. This study aimed to evaluate the humoral immune response to RZV in immunosuppressed SSc patients compared to healthy controls, to identify factors influencing vaccine response, and to assess RZV safety profile and impact on patient-reported outcome measure (PROM) using validated scores.

Methods: In this randomized, double-blind, placebo-controlled trial, 76 immunosuppressed SSc patients (≥18 years) and 304 healthy individuals (≥50 years) in control group (CG) received two RZV doses. SSc patients were randomized to vaccine (P1) or placebo (P2) at D0 and D42, with unblinding at D84, after which P2 also received RZV (D84, D126). Anti-glycoprotein E antibody (Anti-gE) levels were measured at baseline and 6-week visit after vaccination using an in-house GlaxoSmithKline (GSK)’s enzyme-linked immunosorbent assay (ELISA). A humoral response was defined as ≥4-fold the pre-vaccination concentration. Geometric mean titers (GMTs) and factor increase (FI) were calculated. PROM and DA was assessed by EULAR Systemic Sclerosis Impact of Disease (ScleroID), Modified Medical Research Council (mMRC) Dyspnea Scale, Clinical Disease Activity Index (CDAI), and patient/provider’s global assessments

Results: Female sex was similar between groups (p >0.05). SSc patients were younger [53.0 (46.0-61.0) vs 55.0 (52.0-61.0), p=0.002] years, more often Black (44.1 vs 19.4%, p< 0.001), had lower body mass index (p=0.005), and more chronic kidney disease (p=0.001). At 6-week visit after the 2nd dose, humoral response was observed in 92.6% of SSc and 99.7% of CG (p=0.001). SSc had a significantly lower GMT [5.8 (95% CI 4.4-7.7) vs 12.6 (95% CI 11.6-13.6), p< 0.001], and FI at D84 [31.0 (95% CI 20.6-46.6) vs 59.4 (95% CI 51.4-68.8), p< 0.001] compared to CG (table 1). No demographic or immunosuppressive therapy predicted impaired vaccine response. Local adverse events were less frequent in SSc patients (73.7 vs 86.5%, p=0.024) with significantly low rates of pain, erythema and edema at injection sites (p< 0.05). Systemic reactions were comparable overall (59.2 vs 61.5%, p=0.712), although dyspnea (p< 0.001), tremor (p=0.018) and vomiting (p=0.032) were more common among SSc patients. DA parameters and PROM (ScleroID, mMRC, CDAI, and patient/provider's global assessments) showed no significant differences between vaccinated (P1) and placebo (P2) groups at baseline, D42, D84 (p >0.05). Rates of worsening across validated DA measures were similar between groups at all time points (p >0.05) (Table 2).

Conclusion: RZV is safe and highly immunogenic in immunosuppressed SSc patients, without affecting DA as measured by validated scores. However, lower antibody titers raise concerns about long-term protection, underscoring the need for ongoing monitoring in this population (ClinicalTrials NCT05879419).

SSc – systemic sclerosis; CG – control group; GMTs – Geometric mean titers (AU/mL); Frequencies of humoral response are presented as number (%) and they were compared using two-sided chi-square test between SSc and CG at D84 (12-week after first vaccine dose). Ig-gE IgG titers and factor increase in GMT are expressed as geometric means with 95% confidence interval (95%CI). Data regarding anti-gE titers were analyzed using ANOVA with repeated measures and 2 factors [2 groups (SSc vs. CG), at 2 time points (D0 and D84)], followed by Bonferroni’s multiple comparisons at neperian logarithm (ln)-transformed data. GMT and factor increase in GMT were compared using Mann-Whitney test for intergroup comparisons in ln-transformed data at pre-specified time points (D0 and D84). All analyses were two-side

PtGA – Patient’s Global Assessment; PrGA – Provider’s Global Assessment; ScleroID – EULAR Systemic Sclerosis Impact of Disease questionnaire; CDAI – Clinical Disease Activity Index; mRSS – Modified Rodnan Score; mMRC – Modified Medical Research Council Dyspnea Scale. Deterioration in established validated assessment tools were defined: increase in ScleroID of ≥ 0.48; CDAI > 6.5; mRSS ≥ 5; mMRC ≥ 1. Mann-Whitney test was used for intergroup comparison.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/first-prospective-evaluation-of-recombinant-herpes-zoster-vaccine-in-systemic-sclerosis-immunogenicity-safety-and-disease-activity-outcomes/