Zoster Vaccine Shows Strong Effectiveness in Patients With Multiple Sclerosis

A retrospective cohort study published in Multiple Sclerosis Journal found that the recombinant zoster vaccine (RZV) was 64% to 81% effective at preventing herpes zoster (HZ), or shingles, in adults with multiple sclerosis (MS), using data from more than 71,000 patients across Medicare and commercial insurance claims. The findings come from a planned interim analysis of an ongoing study registered with the European Medicines Agency (EU PAS number EUPAS107073).^1,2

Why HZ risk matters in MS

HZ results from reactivation of the varicella zoster virus and affects roughly one-third of people at some point in their lives; while the rash is self-limited, 10% to 18% of cases develop persistent pain, and rarer complications include vision loss, encephalitis, and nerve palsies.³ Risk rises substantially after age 50 but is also elevated in younger, immunosuppressed adults, including those with MS: one study found HZ rates roughly 1.3 to 2.8 times higher in people using MS therapy compared with the general population, and an FDA adverse event database analysis found higher odds of HZ reports among users of MS disease-modifying therapies relative to users of other medications.^4,5

The FDA first approved RZV for adults 50 and older in October 2017, then expanded approval in July 2021 to adults 18 and older at increased HZ risk due to immunodeficiency or immunosuppression; the Advisory Committee on Immunization Practices recommended RZV for all immunocompromised adults 19 and older in October 2021.⁶

The American Academy of Neurology's practice guidelines emphasize vaccination against preventable infections in people with MS, and a joint ECTRIMS/EAN consensus statement specifically recommends RZV for patients with MS on immunosuppressive therapy.^7,8 Despite this guidance, only about 7% of people with MS in the US have received a dose of RZV, and real-world effectiveness data in this population have been limited.^1,9

Findings

The Medicare cohort included 8705 vaccinated and 34,407 unvaccinated patients with MS, while the commercially insured cohort included 6025 vaccinated and 22,685 unvaccinated patients; most patients in both cohorts were 50 or older.¹ Crude HZ incidence among unvaccinated patients was 13.7 and 12.7 per 1,000 person-years in the Medicare and commercial cohorts, respectively, compared with 4.6 and 2.4 per 1,000 person-years among vaccinated patients.¹

After weighting, RZV was 64% effective (95% CI, 51%-74%) in the Medicare cohort and 81% effective (95% CI, 70%-88%) in the commercially insured cohort.

"Our study of patients with MS demonstrates robust protection of RZV against HZ," the study authors, led by Sheryl A. Kluberg, PhD, a Research Scientist in the Department of Population Medicine at Harvard Medical School, wrote, noting the results are particularly notable given that patients with MS were excluded from RZV's original phase 3 randomized trials.¹

Study design

Using US administrative claims formatted to the FDA's Sentinel Common Data Model, researchers identified adults 18 and older with pre-existing MS (defined by a validated claims-based algorithm) who received 2 RZV doses at least 28 days apart between January 2018 and either December 2021 (Medicare) or September 2023 (commercial insurers).

Each vaccinated patient was matched to up to 4 unvaccinated comparators by insurer, sex, age, and calendar date, and researchers used inverse probability of treatment weighting to balance the groups across a wide range of demographic and clinical covariates, including MS disease severity, comorbidities, and prior vaccination history. Follow-up began 31 days after the second dose to allow time for immune response.

Context from other populations

The effectiveness seen in this study falls within the range reported in the general population 50 and older without immunosuppression, where RZV showed greater than 90% efficacy in clinical trials and 70% to 88% effectiveness in real-world studies. It's also broadly consistent with effectiveness estimates in other autoimmune and immunosuppressed populations: prior real-world studies have reported RZV effectiveness of 63% or higher in inflammatory bowel disease, 60.7% to 62.8% in rheumatoid arthritis, 54% to 70% in systemic lupus erythematosus, 77.2% in psoriasis, and 65.6% in psoriatic arthritis, while clinical trials in stem cell transplant recipients and patients with hematologic malignancies showed 68% and 87% efficacy, respectively.¹

Only one prior study had reported RZV effectiveness specifically in an MS subgroup, finding a lower estimate of 48.1% (95% CI, 12.7%-69.1%) among commercially insured patients 50 and older, though with a considerably wider confidence interval than the current study. The authors noted that the higher effectiveness observed in their commercially insured cohort compared with their Medicare cohort could reflect chance, given overlapping confidence intervals, or true differences in age, comorbidities, or disease severity between the 2 populations.¹

Limitations

The authors cautioned that claims data are subject to misclassification, that prescribed therapies may not always have been taken as directed, and that sample size limitations prevented analysis of how specific immunosuppressive therapies, such as B-cell-depleting drugs, might affect vaccine effectiveness; those subgroup analyses are planned for the final study. The authors also noted that vaccinated patients had fewer comorbidities and lower baseline hospitalization rates before weighting, raising the possibility that an unmeasured "healthy user" effect could have inflated the effectiveness estimates despite adjustment.¹

REFERENCES
1. Kluberg SA, Mayer SE, Spence O, et al. Effectiveness of the recombinant zoster vaccine in adult patients with multiple sclerosis: A claims-based retrospective cohort study in the United States. Mult Scler. 2026. doi:10.1177/13524585261468620
2. RWD Catalogues. Safety and effectiveness of RZV in adults ≥18 years of age with systemic lupus erythematosus (SLE) or multiple sclerosis (MS) (EPI-ZOSTER-041 VS US DB 215104). European Medicines Agency. Accessed August 13, 2026. https://catalogues.ema.europa.eu/node/3879/administrative-details
3. Centers for Disease Control and Prevention. Clinical Overview of Herpes Zoster (Shingles). Updated 2024. Accessed August 13, 2026. https://www.cdc.gov/shingles/hcp/clinical-overview/index.html
4. Manouchehrinia A, Tanasescu R, Kareem H, et al. Prevalence of a history of prior varicella/herpes zoster infection in multiple sclerosis. J Neurovirol. 2017;23(6):839-844. doi:10.1007/s13365-017-0575-y
5. Langer-Gould AM, Smith JB, Gonzales EG, et al. Multiple sclerosis, disease-modifying therapies, and infections. Neurol Neuroimmunol Neuroinflamm. 2023;10(6):e200164. doi:10.1212/NXI.0000000000200164
6. Anderson TC, Masters NB, Guo A, et al. Use of recombinant zoster vaccine in immunocompromised adults aged ≥19 years: Recommendations of the Advisory Committee on Immunization Practices — United States, 2022. MMWR Morb Mortal Wkly Rep. 2022;71(3):80-84. doi:10.15585/mmwr.mm7103a2
7. Farez MF, Correale J, Armstrong MJ, et al. Practice guideline update summary: Vaccine-preventable infections and immunization in multiple sclerosis. Neurology. 2019;93(13):584-594. doi:10.1212/WNL.0000000000008157
8. Otero-Romero S, Lebrun-Frénay C, Reyes S, et al. ECTRIMS/EAN consensus on vaccination in people with multiple sclerosis. Mult Scler. 2023;29(8):904-925. doi:10.1177/13524585231168043
9. Gatwood J, McGuiness CB, Yasuda M, et al. P-29. Recombinant zoster vaccine uptake among immunocompromised US adults. Open Forum Infect Dis. 2025;12(suppl 1):ofae631.236. doi:10.1093/ofid/ofae631.236