Background: The 2019 EULAR recommendations on vaccination for adult patients with rheumatic immune-mediated inflammatory diseases (IMIDs) concluded that these patients are at increased risk of herpes zoster (HZ) compared to the general population [1]. However, the current EULAR guideline lacks clarity and specificity, and is very cautiously phrased. This might cause physicians to underestimate the importance of HZ vaccination for IMID patients, which could result in suboptimal protection against HZ. Since the formulation of the 2019 EULAR guidelines, new data on HZ in IMID patients has been published. Additionally, a recombinant HZ vaccine (RZV) has become available, which can be given to IMID patients in a more accessible manner compared to the original live-attenuated HZ vaccine. Hence, current EULAR vaccination guidelines for HZ may therefore be outdated as HZ vaccination might warrant more attention in clinical practice.

Objectives: To evaluate existing evidence on risk factors for HZ and the safety and efficacy of the recombinant vaccine in patients with rheumatic IMIDs, and to discuss the necessity of HZ vaccination for these patients.

Methods: Studies on HZ infection included for the systematic literature review supporting the 2019 EULAR guidelines for vaccination of adult patients were evaluated. In addition, two literature searches were performed using PubMed to include studies published between 2018 and September 2023. Outcome variables were the incidence of HZ in adult patients with rheumatic IMIDs (search 1) and the safety and efficacy of RZV in patients with rheumatic IMIDs (search 2).

Results: Pooled analyses of the systematic literature review (SLR) supporting the 2019 EULAR guidelines showed that the incidence of HZ ranged from 6.7 to 21.3 and 6.4 to 37.7 per 1000 patient years in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) respectively, which corresponded to a two- and fourfold increased risk compared to the general population (pooled IRR 2.3 [95% CI: 2.1-2.6] and 4.0 [95% CI: 2.3-5.7] in RA and SLE patients respectively). In addition, two nationwide cohort studies showed an increased risk of HZ in patients with inflammatory myositis (adjusted HR: 3.90 [95% CI: 3.18 – 4.77]) and patients with primary Sjogren’s syndrome (adjusted HR: 1.69 [95% CI: 1.50 – 1.90]) compared to the general population. Glucocorticoids increase the risk of HZ in a dose-dependent matter (21-24), which was already described in the SLR of the 2011 and 2019 guidelines, but without consequences for HZ vaccination recommendations. Data on JAK-inhibitors were still scarce at the time when the 2019 EULAR guidelines were formulated, but since then, multiple well-powered studies have demonstrated that treatment with these drugs substantially elevated the risk of HZ (range HR 1.98 to 4.00 in studies comparing JAK inhibitors to csDMARDs. Lastly, results from studies the safety and efficacy of RZV in IMID patients are reassuring; adverse events were mild, disease flares were infrequent and efficacy was similar to people from the general population (90.5% in IMID patients with a mean age of 68.8 years vs. 97.2% and 89.9% in healthy people with a mean age of 62.4 and 75.6 years respectively).

Conclusion: With the development of RZV, the benefits of HZ vaccination in patients with rheumatic IMIDs seem to far outweigh the risks and therefore warrant increased attention in clinical practice. We therefore advocate for rheumatologists to systematically recommend HZ vaccination to their adult patients, paying particular attention to patients with SLE and those treated with JAK-inhibitors or glucocorticoids. This will be an important step in protecting patients with rheumatic IMIDs against HZ and its complications.

REFERENCES: [1] Furer V, Rondaan C, Heijstek M, Van Assen S, Bijl M, Agmon-Levin N, et al. Incidence and prevalence of vaccine preventable infections in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD): a systemic literature review informing the 2019 update of the EULAR recommendations for vaccination in adult patients with AIIRD. RMD Open. 2019 Sep 1;5(2).

Acknowledgements: NIL.

Disclosure of Interests: None declared.