TOPLINE:

A recombinant vaccine against herpes zoster (Shingrix) did not increase short‑term disease flares and had an acceptable short-term safety profile in patients with autoimmune rheumatic diseases. Patients had a robust immune response overall but lower antibody titers than healthy individuals.

METHODOLOGY:

• Researchers conducted a double-blind, randomized, phase 4 noninferiority trial to assess whether the recombinant herpes zoster vaccine affected disease activity in patients with autoimmune rheumatic diseases and to evaluate vaccine safety and immune responses.
• They included adult patients with autoimmune rheumatic diseases on stable immunosuppressive therapy at a tertiary center in Brazil between May 2023 and November 2024.
• Patients were randomly assigned to receive either two vaccine doses (n = 590) or two placebo doses (n = 602), and 380 healthy control individuals received two vaccine doses; all injections were spaced 6 weeks apart, and placebo recipients later participated in a crossover into the open-label vaccine phase. The median age of all recipients was 50-56 years, and 77%-80% were women.
• The primary outcome was number of patients with worsening (flare) of disease activity up to day 84 after the first dose. The vaccine was considered noninferior if the upper bound of the one-sided 95% CI for the difference in flare rates between groups was below 5%.
• Secondary outcomes included local and systemic adverse events and immunogenicity, assessed using anti-glycoprotein E antibody levels and CD4⁺ T-cell responses, 6 weeks after the second dose.

TAKEAWAY:

• By day 84, 14% of vaccine recipients and 15% of placebo recipients had a disease flare; the between-group difference was -1.2%, meeting the noninferiority criterion (P for noninferiority = .0018).
• Most patients reported mild local or systemic reactions (77% after the first dose and 72% after the second dose), which were fewer than in healthy control individuals (90% and 81%, respectively). Serious adverse events occurred in 1%-2% of patients, with similar rates observed in both groups.
• A humoral response was mounted in 90% of patients vs 99% of healthy individuals (P < .0001) and postvaccination geometric mean antibody titers were lower in patients (P < .0001). Counts of glycoprotein E‑specific CD4+ T cells increased similarly in both groups 6 weeks after the second dose.
• Factors independently associated with lower postvaccine antibody responses were treatment with rituximab or mycophenolate mofetil, a diagnosis of systemic autoimmune myopathies, and higher baseline anti‑glycoprotein E antibody levels.

IN PRACTICE:

“These results reinforce the role of recombinant zoster vaccine as an effective preventive strategy for patients with autoimmune rheumatic diseases who are at high risk of herpes zoster infection,” the authors of the study wrote.

“As vaccine hesitancy varies across autoimmune rheumatic diseases with different predilection for severe organ manifestations, this trial cannot totally allay the concerns regarding disease flares and their potential consequences in certain autoimmune rheumatic diseases such as SLE, systemic vasculitides, and the inflammatory myopathies,” experts wrote in a comment.

SOURCE:

The study was led by Nadia E. Aikawa, MD, PhD, and Ana C. Medeiros-Ribeiro, MD, PhD, Universidade de Sao Paulo, Sao Paulo, Brazil. It was published online on February 9, 2026, in The Lancet Rheumatology.

LIMITATIONS:

Definitions of disease worsening varied across conditions, which may have limited the assessment of flares. The trial was not adequately powered to detect subgroup differences or to measure an effect on actual shingles cases. Researchers did not stop disease‑modifying drugs, which likely reduced antibody responses and limited conclusions about optimal vaccination timing.

DISCLOSURES:

The study received funding from GSK, which supplied the vaccine and reagents for immunogenicity testing. Additional support came from the Fundação de Amparo à Pesquisa do Estado de São Paulo and the Conselho Nacional de Desenvolvimento Científico e Tecnológico. The authors declared having no competing interests.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.