Recombinant Adjuvanted Herpes Zoster Vaccine is Safe, Study Shows

Rheumatologists should feel more confident in recommending vaccination against herpes zoster to patients with rheumatoid arthritis after a study suggested that the recently approved recombinant adjuvanted vaccine was well tolerated in this group of patients. 

The study, published in ACR Open Rheumatology,  showed that rates of side effects experienced by the patients with rheumatic conditions were similar to those seen in patients in the pivotal clinical trials, and that the vaccine did not prompt flares of rheumatoid conditions.

The lifetime risk of getting shingles is around one in three in the United States, and risk of the condition grows with age. Taking immunosuppressant medications, such as corticosteroids, methotrexate, biologic disease-modifying agents, and janus kinase inhibitors, also heightens the risk.

Despite this, uptake of vaccination against herpes zoster has historically been low in patients with rheumatic diseases, says Sonali Desai, MD, MPH, from the Division of Rheumatology, Immunology, and Allergy, Department of Medicine, at Brigham and Women's Hospital, Boston, MA. “There is always a concern with autoimmune diseases that a vaccine might perpetuate or cause a flare up of the underlying rheumatological condition, so there is a hesitancy as to whether the risk-benefit of vaccination versus non-vaccination makes sense,” she said.

And, until recently, only a live vaccine against herpes zoster has been available, which had an overall efficacy of just 51% and could not be administered to patients taking concomitant immunosuppressive therapies, including corticosteroids. This made administration to patients with rheumatological diseases difficult, Desai explains, meaning uptake rates were very low - less than 10%. “We had to stop their biologic therapy, wait four weeks, give the vaccine, wait another four weeks, then they would be okay. That was very logistically complicated.”

A recombinant adjuvanted vaccine for herpes zoster with a greater efficacy rate-of more than 90% in over 60s-was approved by the U.S. Food and Drug Administraton in 2018. However, many rheumatologists have been hesitant to it, as the pivotal trials excluded immunocompromised patients and there are no guidelines recommending the vaccine.  The current American College of Rheumatology guidelines on rheumatoid arthritis were published in 2015, before the vaccine was available; they are due to be updated in the fall this year.

“With that knowledge gap people are more hesitant without that prior recommendation,” Desai says.
However, she and her colleagues have given the vaccine routinely since it was approved. “It seemed to make sense because it wasn’t live,” she says.

An analysis of data on 403 patients (239 patients with rheumatoid arthritis and 164 patients with other systemic rheumatic disease) given the vaccine between February 1, 2018 and February 1, 2019 was assessed for the study. The results showed that a total of 6.7% (n = 27) of patients experienced flares, and 12.7% experienced side effects.

All flares and side effects were regarded as mild. The rate of side-effects was similar to that seen in the pivotal trails, and the incidence of flare ups was lower than the background rate expected.

Based on the results of this real world data, Desai would recommend the vaccination for patients with rheumatoid arthritis. “We’ve not found any major increase risk of adverse reactions or flare ups, at least in our experience,” she says. “When we know something is common and that there is a relatively safe vaccine that can reduce the incidence and the population that we are treating is more likely to be susceptible then it seems to make sense to try to alleviate that.”

Three patients who received the vaccine developed herpes zoster. Desai points out that the vaccine is not 100% effective and that two of the patients were taking tofacitinib which is associated with a greater risk of herpes zoster. She adds that it is unlikely that vaccination was linked to infection, as in two of the patients it did not occur until almost a year later.