Rheumatoid arthritis

Shingles vax should be priority for JAK inhibitor treated  patients

Shingles vaccination should be considered for older patients with rheumatoid arthritis, according to European researchers who have shown that JAK inhibitor therapy is associated with an almost four-fold higher risk of herpes zoster compared to conventional synthetic DMARDs.

German investigators reviewed the risk of herpes zoster in almost 14,000 patients with RA receiving DMARD treatment between 2007 and 2020.

Their review confirmed that risk of herpes zoster increased with age and with higher dose glucocorticoid therapy (>10mg).

After adjusting for these factors, their analysis showed that the risk of herpes zoster was significantly increased with targeted synthetic DMARDs (Hazard Ratio 3.66), monoclonal anti-TNF antibodies (HR 1.63) and rituximab (HR 1.57) compared with csDMARDs.

Based on 559 cases of herpes zoster that developed in 533 patients the exposure-adjusted event rates (EAER) per 1000 patient years were 21.5 for JAK inhibitors such as tofacitinib, baricitinib and upadacitinib; 10.3 for B cell targeted therapy (rituximab) and 9.3 for monoclonal anti-TNF antibodies (adalimumab, certolizumab, golimumab and infliximab).

The EAER for IL-6 inhibitors (tocilizumab, sarilumab) was 8.8, while the rates for soluble TNF receptor fusion protein (etanercept) and T cell costimulation modulator (abatacept) were 8.6 and 8.1 respectively. The reference group, csDMARDs had herpes zoster rates of 7.1.

Writing in Annals of Rheumatic Diseases, the investigators said previous studies from the US and elsewhere had suggested an increased risk of herpes zoster with JAK inhibitors compared to biologic DMARDs, but much of the data had come from earlier periods when  JAK inhibitors were not in such widespread use.

They said the recent data suggested that the risk of herpes zoster may vary depending on the mode of action of DMARDs.

With JAK inhibitors modulating the immune response by blocking intracellular signals on the cytokine level, the downregulation of interleukin 12, IFN-γ and other relevant cytokines may enable the reactivation of latent viral infections, they postulated.

They noted that groups such as EULAR recommend herpes zoster vaccination in high-risk patients with autoimmune rheumatic disease, but data suggested only a small proportion of patients have been vaccinated.

“In terms of a risk assessment with regard to vaccination, this suggests that especially elderly patients with higher glucocorticoid doses and patients for whom tsDMARD therapy is planned should be considered for vaccination,” they concluded.

In Australia, the non-live, recombinant subunit vaccine Shingrix recently became available on the private market as a safer alternative to the live vaccine Zostavax in immunocompromised patients.

Shingrix is recommended  is indicated to help prevent herpes zoster and post-herpetic neuralgia in people aged 50 years or older. According to the Australian Technical Advisory Group on Immunisation (ATAGI), Zostavax is generally contraindicated in immunocompromised adults aged ≥50 years and Shingrix should be used.

However, despite being listed on the Immunisation Schedule, Shingrix is not funded on the National Immunisation Program, which only has Zostavax  funded for people who are 70 years of age.

Professor Tony Cunningham, Director of the Centre for Virus Research (WIMR) at Sydney University,  told the limbic that about 60% of Australians in the eligible age group [70–79] have taken up the Zostavax but it was not an option for people who were moderately to severely immunocompromised, who would instead have to pay several hundred dollars for Shingrix.

He said he would like to see Shingrix funded for at-risk groups, but this would require the vaccine to be approved by the Pharmaceutical Benefits Advisory Committee (PBAC).

“I haven’t heard [regarding a timeframe on PBAC re-application]. They’ve tried once, and the company and the Government haven’t come to an agreement,” he said.

“Personally, I’d like to see further negotiations between the company and Government to arrive at a compromise position where it could, like Zostavax, be on the National Immunisation Program.”

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