Recombinant Herpes Zoster Vaccine in Patients With Autoimmune Rheumatic Diseases

Summary

Introduction: Patients with autoimmune rheumatic diseases (ARDs), rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), psoriatic arthritis (PAs), ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), primary Sjögren's syndrome (pSS) , systemic sclerosis (SSc), idiopathic inflammatory myopathies (IIM) and primary vasculitides, have a high risk of herpes zoster (HZ) infection. This increased susceptibility is caused by a deficient cell-mediated immune response due to the underlying disease and glucocorticoid and immunosuppressive treatments that impair the T-cell response, including conventional and unconventional synthetic disease-modifying anti-rheumatic drugs (DMARDs) and biological agents. In this context, the recent availability of a recombinant vaccine against HZ (RZV or Shingrix®), composed of recombinant VZV glycoprotein E (gE) and the AS01B adjuvant system (HZ/su), is a major progress regarding safety for immunosuppressed patients. Its effectiveness, however, has been clearly demonstrated for non-immunosuppressed patients and in selected populations of immunocompromised individuals. There are no prospective controlled studies evaluating the immunogenicity of RZV and its impact on the activity of the underlying disease, as well as its safety in patients with ARDs at high-risk for HZ. Hypothesis: RZV has a good safety profile, including with respect to underlying rheumatic disease activity, in patients with ARDs at high risk of HZ. Objectives: Primary: To assess the short-term safety profile in relation to underlying disease activity in patients with ARDs at high risk of HZ immunized with RZV compared to unvaccinated patients. Secondary: To evaluate the general safety of the vaccine in patients with ARDs at high risk of HZ immunized with RZV and non-immunosuppressed control subjects (CG); the humoral and cellular immunogenicity of RZV in patients with ARDs at high risk of HZ compared to CG; the influence of disease treatment on vaccine response; the 12-month persistence of humoral immunogenicity and incident cases of HZ. Specific studies will also be carried out to evaluate the effect of drug withdrawal (methotrexate-MTX and mycophenolate mofetil-MMF) after vaccination in increasing the immune response in patients with ARDs with controlled underlying disease. On November 19, 2025, the institutional Ethics Committee approved an amendment to extend the project's timeframe to evaluate the following hypothesis: \- Immunosuppression may hamper 5-year long-term sustainability of humoral and cellular immune responses to RZV in ARD patients. No new patients will be recruited, nor will any new intervations be performed. ARD patients previously included in the study and non-immunosuppressed control subjects who received both vaccine doses and collected samples for immunogenicity 6 weeks and one year after the second dose will be part of the proposed extension. A total of 1,025 ARD patients enrolled and 365 healthy controls will be included in the long-term follow-up phase. Considering a conservative 10% dropout, the final patient sample will be approximately 1,000. Ethical statement: The extension protocol was approved by the institutional Ethics Committee (report 7.988.896), and written consent will be obtained from all participants prior to inclusion. Humoral immunogenicity will be evaluated by analyzing the serum concentrations of anti-gE antibodies (ELISA) of blood samples collected from participants at 5-year after complete VZR vaccination, as previously described (Cunningham et al., 2018). Cellular immunogenicity will be evaluated in a convenience sample (20% of the total research participants) of patients with ARDs and healthy controls at 5-year after complete VZR vaccination. Vaccine efficacy will be evaluated by incident cases of HZ in the period of 5 years after RZV vaccination. Participants will be followed for 5 years after the second RZV dose through monthly contacts and routine clinical visits every 3-6 months.

Timeline

Start

2023-05-23

Primary completion

2025-12-01

Completion

2032-06-30

Publications

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• Pasoto SG, Gorayeb THB, Luppino-Assad AP, Aikawa NE, Medeiros-Ribeiro AC, Kupa LVK, Borges BS, Shinjo SK, de Souza FHC, Miossi R, Bonfa E, Silva CA. Immunogenicity, Safety, and Determinants of Recombinant Zoster Vaccine Response in Idiopathic Inflammatory Myopathies: A Phase 4 Randomized Trial. Arthritis Care Res (Hoboken). 2026 Jun 15. doi: 10.1002/acr.80103. Online ahead of print.
• Luppino-Assad AP, Mello RP, Medeiros-Ribeiro AC, Aikawa NE, Pasoto SG, Praxedes AC, Kupa LV, Miossi R, Sampaio-Barros PD, Borba EF, Bonfa E, Silva CA. Prospective evaluation of recombinant Herpes zoster vaccine in SSc: immunogenicity, safety and disease outcomes. Rheumatology (Oxford). 2026 Jun 3;65(6):keag294. doi: 10.1093/rheumatology/keag294.
• Pasoto SG, Ribeiro TO, Aikawa NE, Medeiros-Ribeiro AC, Borges BDS, Franco AS, Silveira CGT, da Silva HC, Bonfa E, da Silva CAA. Lower magnitude of humoral response to recombinant herpes zoster vaccine in immunocompromised Sjogren's disease patients: evidence from a randomized double-blinded placebo-controlled trial. Semin Arthritis Rheum. 2026 Jun;78:152974. doi: 10.1016/j.semarthrit.2026.152974. Epub 2026 Mar 24.
• Aikawa NE, Medeiros-Ribeiro AC, Pasoto SG, Kupa LVK, Seguro LPC, Luppino-Assad AP, Borba EF, Saad CGS, Yuki EFN, Andrade DCO, Shimabuco AY, Bonfiglioli KR, Domiciano DS, Moares JCB, Shinjo SK, Sampaio-Barros PD, Giardini HAM, de Oliveira JCS, Antonelli IPB, Mello RLP, Gorayeb TB, Farias LGN, Negrini AA, Chaer FGG, Praxedes ACSL, Lopes MH, Silva CA, Bonfa E. Recombinant herpes zoster vaccine in patients with autoimmune rheumatic diseases in Brazil: a double-blind, randomised, placebo-controlled, phase 4, non-inferiority study. Lancet Rheumatol. 2026 May;8(5):e363-e376. doi: 10.1016/S2665-9913(25)00313-3. Epub 2026 Feb 9.

Drugs

Indications