Effectiveness of Adjuvanted Recombinant Zoster Vaccine (RZV) against Postherpetic Neuralgia (PHN) and against Cardiovascular Disease (CVD) Events after Herpes Zoster (HZ) in United States Adults in Medicare Fee-for-Service (FFS) + Inovalon’s MORE2 Registry

≥50 years, RZV 2-dose 2-6 months cohort An older adult cohort of all individuals in the Medicare FFS and MORE2 databases who received RZV vaccination in the study period based on age (≥50 years) and as recommended i.e., 2 doses 2-6 months apart, 1:1 matched to an RZV unvaccinated comparator. Adults ≥65 YOA from Medicare FFS are a subpopulation of Cohort #1. To be eligible for inclusion in cohort #1, a participant must meet all the following criteria:

• Receipt of 2 doses of RZV, 2-6 months apart for the RZV exposed group and at least one preventive care visit with no prior RZV for the RZV unvaccinated comparator. o The index date will be set to the second claim for RZV exposed or the preventive care visit for the RZV unvaccinated comparator.
• Age ≥50 years on the index date.
• Continuously enrolled with medical and pharmacy benefits for at least 365 days preceding the index date. o Medicare FFS databases: enrolled in Medicare Part A (hospitalization), B (office-based care) and Part D (prescription drug coverage). Continuous enrollment is determined by enrollment in the month of the index date and enrollment in at least 11 of the 12 preceding months, i.e., allowing a maximum of one calendar month gap in enrollment. o MORE2: Commercial insurance, Medicare Advantage, or Medicaid. Continuous enrollment is determined by no more than 30-day administrative gaps in coverage.
• Continuously enrolled with medical and pharmacy benefits for at least 30 days following the index date. Note that a participant initially included in the RZV unvaccinated comparator group may later be classified in the RZV exposed group after their qualifying preventive care visit, if they receive RZV vaccination per the definition of the RZV exposed group and meet inclusion criteria. Cohort #2 – ≥18 years IC/AID, RZV 2-dose 1-6 months cohort An adult cohort of individuals in the Medicare FFS and MORE2 databases ≥18 years who have an IC/AID and received RZV vaccination in the study period and as recommended i.e., 2 doses 1-6 months apart, 1:1 matched to an RZV unvaccinated comparator. IC/AID will include IC (hematologic malignancies, HIV/AIDS, solid organ transplant, solid tumors, and bone marrow transplant) and AID (inflammatory bowel disease, multiple sclerosis, psoriasis, psoriatic arthritis, rheumatoid arthritis, and systemic lupus erythematosus). To be eligible for inclusion in cohort #2, a participant must meet all the following criteria:
• Receipt of 2 doses of RZV, 1-6 months apart for the RZV exposed group and at least one preventive care visit with no prior RZV for the RZV unvaccinated comparator. o The index date will be set to the second claim for RZV for RZV exposed or the preventive care visit for the RZV unvaccinated comparator.
• Age ≥18 years on the index date; Age 18-49 years on index date will only be included starting from 20 October 2021.
• Continuously enrolled with medical and pharmacy benefits for at least 365 days preceding the index date. o Medicare FFS databases: enrolled in Medicare Part A (hospitalization), B (office-based care) and Part D (prescription drug coverage). Continuous enrollment is determined by enrollment in the month of the index date and enrollment in at least 11 of the 12 preceding months, i.e., allowing a maximum of one calendar month gap in enrollment. o MORE2: Commercial insurance, Medicare Advantage, or Medicaid. Continuous enrollment is determined by no more than 30-day administrative gaps in coverage.
• Evidence of IC/AID during the 12-month baseline period preceding the index date: o IC includes hematologic malignancy, HIV/AIDS, solid organ transplant, solid tumor, and bone marrow transplant. AID includes inflammatory bowel disease, multiple sclerosis, psoriasis, psoriatic arthritis, rheumatoid arthritis, and systemic lupus erythematosus.
• Continuously enrolled with medical and pharmacy benefits for at least 30 days following the index date. Note that a participant initially included in the RZV unvaccinated comparator group may later be classified in the RZV exposed group after their qualifying preventive care visit, if they receive RZV vaccination per the definition of the RZV exposed group and meet inclusion criteria.

The following exclusion criteria apply to all cohorts. An individual who meets any of the following criteria will be excluded from this study:

• History of ZVL any time prior to the index date (not limited to 1 year prior to the index date).
• HZ diagnosis in inpatient, emergency department (ED), or outpatient setting in the 1 year (365 days) prior to the index date or in the 30 days after index date.
• In a skilled nursing facility or on hospice in the 1 year (365 days) prior to or on the index date.
• Medicare FFS database: Original reason for entitlement to Medicare is based on disability insurance benefit, end-stage renal disease, or disability benefit and end-stage renal disease. Note that for each analysis, individuals presenting evidence of the outcome of interest in the 1 year (365 days) prior to the index date or in the 30 days after index date will be excluded from that analysis.