Making sense of zoster vaccination in the immunocompromised: ‘It’s all about treatment’
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Protecting immunocompromised individuals from infections like herpes zoster is an ongoing challenge for every rheumatologist.
However, while it is known that patients who are immunocompromised are at increased risk for the disease, and that the recombinant zoster vaccine is safe and effective in the general population, myriad questions remain. For example, does the vaccine work the same in immunocompromised populations as in the general population? Additionally, the vaccine’s long-term efficacy has yet to be determined. Lastly, perhaps the most important — and most confounding — task for clinicians is to identify those at greatest risk for this infection.
In a review recently published in the Cleveland Clinic Journal of Medicine, Cassandra Calabrese, DO, in the departments of rheumatic and immunologic disease and infectious disease at the Cleveland Clinic, and Leonard H. Calabrese, DO, RJ Fasenmyer chair of clinical immunology at the Cleveland Clinic, and colleagues, aimed to address these exact knowledge gaps.
“We have had this vaccine for 7 years now, and it is highly effective, but initially recommended only for those aged 50 years and older,” Leonard Calabrese, who is also the chief medical editor for Healio Rheumatology, told Healio. “In 2021, it was also approved for patients 19 years of age and older who are immunocompromised.
“However, that statement of identifying people as immunocompromised is broad and sweeping,” he added. “It lacks granularity. It left many practitioners lacking in the confidence that they understand different degrees of immunocompromise.”
Although recent data have answered some of these questions, ongoing research is necessary to further understand the impact of various types of immunosuppression on HZ vaccine efficacy.
Healio sat down with both Calabreses to discuss the patient populations most at risk for HZ, topics to discuss with patients about the vaccine, and what clinicians can expect in terms of long-term protection.
Healio: What was the impetus for writing this paper?
Leonard Calabrese (LC): There are questions of whether the vaccine works the same in immunocompromised populations as in the general population, whether there are special considerations for administering the vaccine, and how long protection lasts. We hoped to answer those questions in a give-and-take, question-and-answer manner.
Cassandra Calabrese (CC): The good news is that we have follow-up data for 7 years and counting that tells us the vaccine is effective in other challenging populations, such as those who are as old as 80 or 90 years. We just still do not know how durable protection is in our immunocompromised patients.
Healio: Were patients who are immunocompromised included in trials leading up to the approval of the vaccine?
CC: They did include a small group of patients with various autoimmune diseases but no patients who were significantly immunocompromised. There are few real-world data to guide us in the management of our patients.
Healio: If there are recent, real-world data, what do they show?
LC: The two studies we cite that are most thoroughly performed showed that the recombinant zoster vaccine was effective in two immunocompromised patient groups — those who have undergone bone marrow transplant and those with hematologic malignancies. The results showed somewhat lower vaccine efficacy but still relatively high protection over period of observation.
CC: There have also been some smaller studies showing effectiveness in patients with HIV, as well as patients with solid organ transplant, which is encouraging.
Healio: When do you expect long-term data in patients who are immunocompromised to emerge?
CC: This work is currently under way but the vaccine has only been approved for younger immunocompromised persons for 3 years, so it will be some time.
Healio: Can you address the differences between patients who are immunocompromised due to bone marrow transplantation or hematologic malignancies, and those rheumatologists see every day?
CC: This is the challenge. Our patient population is complex and very heterogeneous. You cannot just lump them together the way you can with patients who have undergone transplant. There are variables from disease to disease, there are variables in the medications used to treat the diseases and the disease itself, and there are variables in the drug combinations we use.
This is where the confusion comes in. Not all of our patients need a recombinant zoster vaccine before they are 50 years old — only those at higher risk, which is dependent on immunosuppressive regimen.
Healio: Which groups are at the highest risk for zoster and are the best candidates for this vaccine earlier than age 50 years?
LC: We outlined all of these categories of immunocompromised patients in the article. Within our patient population, there is a tremendous gradation, from people who are most immunocompromised and those who are least immunocompromised.
CC: Patients on JAK inhibitors are at a very high risk for zoster. Also, those taking anifrolumab (Saphnelo, AstraZeneca). They are at the top of the list. Those taking moderate-dose glucocorticoids are at risk as well.
LC: Beyond that are a number of combinations. Saying they are immunocompromised and leaving it at that simply is not the answer in the rheumatology world. It’s all about treatment.
Healio: Will this document lead to further recommendations for the recombinant zoster vaccine in the rheumatology setting?
LC: There are clear recommendations in the ACR vaccination guidelines from a year or so ago, but they do not go into enough granularity about the zoster vaccine. That is what our article is trying to do.
Healio: What other considerations are included in your article?
LC: One thing that rheumatologists really need to know about is how to address patient concerns about the risk for potential disease flare with vaccination.
CC: The vaccine itself has a very potent adjuvant that ramps up the immune system and causes systemic reactogenicity. Patients can experience fever, chills, body aches and other such events after the vaccination, which is normal. These events are significant and occur in about one in 10 patients, but they are transient. They only last for a day or a few days. It is important for us to counsel patients about these possible outcomes.
Healio: What about disease flare risk?
CC: There are a handful of studies that have looked at this, including our work, and the long and short of it is that there is a slight risk for disease flare after receiving the vaccine, but these flares are mild and manageable, and not at all a reason to avoid the vaccine.
We also found that being on steroids at the time of zoster vaccination was associated with increased risk for flare, so we typically will hold off on administering this vaccine if the patient is experiencing a bad flare of their underlying disease.
LC: Timing is important. If a patient is not doing well with their disease, and if you have the opportunity to hold off on vaccinating them that day, hold off. Also, if you are about to put a patient on an immunosuppressive medication, you should do the vaccine before you initiate that treatment.
Healio: What else is part of the conversation rheumatologists should have with their patients about this vaccine?
CC: We get a wide variety of questions, but probably the most common one is whether they should get the vaccine if they have already had shingles. We have to tell them that if you have had it once, you are at high risk for getting it again.
We also tell them that because of their disease or their medications, they are at higher risk for getting shingles, and if they do get shingles, they are at risk for more severe infection.
However, there are also timing considerations, as Len said. I tell patients if they are going on vacation or getting married, they should not get the vaccine the day before because they might not feel so great for a few days. It is an ongoing discussion that helps improve vaccine uptake as well as the likelihood of patients returning for the second dose.
References:
Calabrese C, et al. CCJM. 2024;doi: 10.3949/ccjm.91a.24019.
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