Effectiveness of the Adjuvanted Recombinant Zoster Vaccine in Patients ≥50 Years with End-Stage Renal Disease in the United States

Patients with end-stage renal disease (ESRD) represent a population with significant immune dysfunction, placing them at increased risk of herpes zoster (HZ). HZ and its complications, including postherpetic neuralgia (PHN), can negatively diminish quality of life. Furthermore, antiviral therapy in ESRD requires dose adjustment and monitoring due to drug accumulation and potential renal toxicity, making prevention a critical strategy. Although the recombinant zoster vaccine (RZV) has demonstrated high efficacy in the general population, ESRD patients were excluded from pivotal clinical trials. Evaluation of RZV effectiveness in ESRD patients is therefore essential. 

This study was conducted at Kaiser Permanente Southern California (KPSC) and included members aged ≥50 years identified from the KPSC ESRD registry. The exposed cohort included those who received 2 doses of RZV, administered ≥4 weeks apart during 04/01/2018 to 12/31/2020. Vaccinated individuals were matched up to 1:4 to unvaccinated individuals on age, sex, race/ethnicity, and time since initiation of dialysis. The index date was the date of receipt of the second dose and was assigned to the matched set. Individuals who were either on dialysis or had already received transplantation on the index date were included. Follow-up ended on the earliest date of membership termination, death, HZ occurrence, receipt of a zoster vaccine, or end of follow-up (12/31/2024). Outcomes were the occurrence of HZ and PHN. HZ was defined by International Classification of Diseases, 10th Revision codes (B02.xx) and PHN was defined as HZ-related pain persisting >3 months after HZ diagnosis identified by targeted chart review from encounter records during >3–6 months after HZ. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) comparing HZ or PHN incidence rates between cohorts were estimated by stratified Cox proportional hazards regression models adjusting for potential confounders. Adjusted vaccine effectiveness (aVE) (%) was calculated as (1−aHR) × 100.  

The study included 493 2-dose RZV vaccinated and 1964 matched unvaccinated individuals (mean age 68.45 years, 38.4% female; Table 1). There were 17 HZ cases in the vaccinated cohort (10.0/1000 person-years; 95% CI: 6.2, 16.1) compared to 115 HZ cases in the unvaccinated group (20.1/1000 person-years; 95% CI: 16.7, 24.1). The aVE against HZ was 56.8% (95% CI: 23.6%, 75.5%). Although not significant, the aVE point estimate appeared higher in individuals ≥70 years (65.6% vs 52.6% in <70 years) and in females (71.6% vs 38.6% in males). Among patients who were on dialysis on the index date, aVE was 73.4% (95% CI: 5.2%, 92.6%) among those on dialysis <2 years versus 50.3% (95% CI: -37.6%, 84.6%) for dialysis ≥2 years. aVE was 59.5% (95% CI: 20.8%, 79.3%) in patients on dialysis on the index date versus 30.6% (95% CI: -36.1%, 69.2%) if patients had already received transplantation (Figure 1). Finally, there were 14 PHN cases (12.2% among HZ cases) in the unvaccinated group compared to zero cases in the vaccinated group. 

Among ESRD patients aged ≥50 years, receipt of 2-dose RZV vaccine was effective against HZ and PHN. In addition, the results suggest HZ vaccination soon after the initiation of dialysis may provide a better protection than delaying vaccination.