From the Journals

Zostavax proves safe, effective in patients with nonactive SLE

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Results are reassuring, but some questions remain

Probably like me you have seen a bit of zoster in our patients with SLE, and rarely we get severe outbreaks in multiple dermatomes or in the eyes or other vulnerable areas in patients on immune suppression. So I think of Zostavax the way I think of shingles per se: The more immune compromised you are, the higher the risk of something bad happening … maybe. But we do know with Zostavax the risk is small.

Dr. Joan T. Merrill

Dr. Joan T. Merrill

The study by Chi Chiu Mok et al. selected stable patients on moderate immune suppression, so I think the paper is pretty reassuring about stable patients. And to the extent that this immunization can stave off a significant outbreak at a later time when maybe the person will be on stronger immune-compromising medications, or is just older with the compromise of weaker defenses, prevention would be good.

Shingrix is a lot more effective than Zostavax and does not have the same issue of potentially causing the thing it prevents. But the most likely reason it works so well is that it has an adjuvant. We are generally a lot more concerned about injecting adjuvants in autoimmune patients here in the United States than they are in Europe where they have more experience with that, but this one is apparently a new adjuvant and has never been used in autoimmune patients, who were excluded from the trials of Shingrix. And a fair number of nonautoimmune patients get autoimmune-like symptoms in the Shingrix trials such as myalgias and fevers. I don’t think we have full confidence yet until we figure out just how worried we ought to be about that. In other words, if Shingrix only causes mild/moderate transient flares, then our patients might rationally consider that a fair trade for lifelong protection.

I think in some patients this is an easier decision than others. If somebody is 50 years old and healthy, hasn’t had nephritis or anything bad before (or not in the last 10 years), and is on no immune suppressant or just using stable, modest doses of such therapies, you would probably recommend doing something to avoid getting zoster. And here you can explain the choice to the patient: Zostavax provides good protection but less than Shingrix, is unlikely to make the patient flare, has very low risk of live vaccine causing much trouble in a generally healthy person; Shingrix is more effective overall, has caused some autoimmune symptoms in healthy people, and has unclear risk for a flare in a patient with a diagnosis (but that can be monitored).

For the sicker patients, we just have to weigh the risk of a natural zoster outbreak against the risk of a flare and the risk of disseminated zoster from the Zostavax, which is a pretty small risk but it is there. It’s a discussion you need to have in advance with each patient. Maybe with some patients, it is best to wait for an optimal time for either choice, when there’s not too much disease and not too much immune-compromising medication.

An unsolved issue for herpes zoster vaccination is age. Greater knowledge about how to best vaccinate would go a long way toward bolstering confidence in using the vaccines in patients a bit younger than 50 years given that zoster does occur in lupus patients at that age.

Joan Merrill, MD, is OMRF Professor of Medicine at the University of Oklahoma Health Sciences Center and a member of the Arthritis & Clinical Immunology Research Program at the Oklahoma Medical Research Foundation, both in Oklahoma City. She is a member of the editorial advisory board of Rheumatology News.


 

FROM ANNALS OF THE RHEUMATIC DISEASES

A live-attenuated herpes zoster vaccine can be used in individuals with systemic lupus erythematosus (SLE) if they are not intensively immunosuppressed and their condition is dormant, research suggests.

A paper published in Annals of the Rheumatic Diseases reported the outcomes of a randomized, placebo-controlled trial of the Zostavax herpes zoster vaccine in 90 adults with clinically stable SLE. Participants had to have been on a stable dose of immunosuppressive agents for at least 6 months and have a history of chicken pox or herpes zoster infection.

Chi Chiu Mok, MD, of the Tuen Mun Hospital in Hong Kong and coauthors wrote that herpes zoster reactivation has been reported to occur in 6.4 to 91.4 individuals with SLE per 1,000 patient-years, with consequences including postherpetic neuralgia and even death from disseminated infection. But because Zostavax is live-attenuated, it has not been widely used in immunocompromised people.

After a single subcutaneous dose of either the vaccine or placebo, researchers saw a significant increase in anti–varicella zoster virus (VZV) IgG antibodies in vaccinated individuals over 6 weeks. The magnitude of the increase in anti-VZV IgG seen in vaccinated individuals was on par with that previously seen in vaccinated healthy controls, although the authors noted that the absolute increase in values was lower.

“While the reason is not apparent, one contributing factor is the high rate of previous exposure to VZV infection in most participants, which could have led to a higher baseline anti-IgG anti-VZV value that limited its rise after vaccination,” the authors wrote.

In contrast, IgG reactivity declined in those who received the placebo injection, and the difference between the two groups was statistically significant after adjustment for baseline antibody titers.

The study also looked at the cell-mediated immune response to the vaccine and found the number of interferon-gamma secreting CD4+ T-cell spots increased in the vaccinated patients but decreased in the placebo arm, and by week 6 it was significantly higher in the treated group. The increase in the vaccine-treated patients was again similar to that previously seen in healthy controls.

However, prednisolone use at baseline may have attenuated the vaccine response. Vaccinated patients who were treated with prednisolone at baseline had a lower increase in T-cell spots and lower anti-VZV IgG reactivity after the vaccination than did those not taking prednisolone, although the difference between the two groups was not statistically significant. The study did not see any effect of age, sex, baseline lymphocyte count, disease activity scores, and other factors on response to the vaccine.

None of the patients who received the vaccine withdrew from the study because of serious adverse events. The most common adverse events reported were injection-site redness and pain, which were more common in the vaccine-treated group than in the placebo group. However these symptoms were mild and resolved by themselves after a few days. Two patients in the vaccine group and one in the placebo group experienced mild or moderate SLE flares.

The authors commented that this was the first randomized, controlled trial examining the safety and immune response of a live-attenuated herpes zoster vaccine in individuals with SLE and this trial showed it was safe and well tolerated in those with stable disease who were not on intensive immunosuppressive therapy.

“Despite the increased risk of HZ [herpes zoster] infection, SLE had the lowest HZ vaccination rates among age-eligible subjects, probably because of the concern of vaccine safety, the principle of contraindication to live-attenuated vaccines in immunocompromised hosts, as well as the current ambiguous guidelines for HZ vaccination in SLE,” they wrote.

But they also stressed that their results did not apply to patients with active disease or on more intensive immunosuppression and that longer-term data on the persistence of vaccine immunogenicity was still being collected.

The study was funded by the Hong Kong Research Fund Secretariat. No conflicts of interest were declared.

SOURCE: Mok CC et al. Ann Rheum Dis. 2019 Sep 17. doi: 10.1136/annrheumdis-2019-215925

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