Herpes zoster (HZ), an exquisitely painful eruption of a skin rash that progresses to vesicles, is caused by the reactivation of latent varicella zoster virus. Occasionally, there can be very serious complications such as eye involvement and neurologic complications, including postherpetic neuralgia (PHN). The incidence of HZ rises with advancing age and is more common in older patients and those who are immunocompromised.
Since 2006, there has been one vaccine available to help prevent HZ, the live-attenuated zoster vaccine (ZVL) (Zostavax). It is approved as a single-dose vaccine in immunocompetent persons of at least 60 years old. Although it was a great advance, it does have some drawbacks.
The HZ prevention efficacy of the ZVL is only about 51 percent and the PHN efficacy is 67 percent. The efficacy of HZ prevention decreases over time, especially over 5-7 years after vaccination. As the risk of HZ increases in older people, it is unclear when then the optimal time for vaccination is to minimize the risk of reactivation. In addition, it is not known if a booster vaccination would be safe or effective.
The weakened cell-mediated immunity (CMI) seen in elderly people, as well in immunocompromised patients, reduces the immune response to vaccine. However, this is also the reason why there is a higher incidence of HZ in these individuals. As it is a live, but attenuated, virus, ZVL is unsafe to give to immunocompromised patients.
New Vaccine
Research has led to the development of a new vaccine, the recombinant zoster vaccine (RZV) (Shingrix). It was FDA-approved late last year for people at least 50 years old. This vaccine is produced by the combination of recombinant subunit varicella zoster virus glycoprotein E and a liposome-based adjuvant.
The efficacy of RZV has been studied in two large trials with immunocompetent people. The RZV is administered in two doses, the second being administered 2-6 months after the first. Pooled efficacy data from the two trials showed a HZ prevention efficacy of 92 percent and a PHN prevention efficacy of 89 percent. The efficacy rates were similar in people over 70 years old compared to that seen with individuals 50-59 years old and 60-69 years old. The most common adverse effects were injection site pain/redness/swelling plus myalgia, fatigue, and headache. Grade 3 reactions were much less common. A cost-effectiveness analysis indicated that the RZV vaccine at the price of $280 per the two-injection series was more effective and less expensive than the ZVL, regardless of the age of the patient.
The CDC recommends RZV vaccination in immunocompetent people or those who are receiving mildly immunosuppressive treatment (i.e., <20 mg/day of prednisone, or inhaled/topical steroids), as well as individuals anticipating immunosuppression or who have recovered from an immunocompromising illness. Immunocompromised patients were excluded from the initial trials of RZV, so a recommendation has not been made for these patients as data is lacking.
From a safety standpoint, as the risk of developing HZ from the RZV is prevented, it may possibly be appropriate for immunocompromised patients. However, the lowered CMI that makes a patient more likely to develop HZ might prevent the patient from mounting an immune response and may make the vaccine less-effective.
There is little published data studying the use of RZV in immunocompromised populations. In one study, RZV was tested in a placebo-controlled trial in 562 patients with hematologic malignancies (e.g., multiple myeloma, Hodgkin lymphoma, chronic lymphocytic leukemia (CLL), non-Hodgkin B-cell lymphoma) who were undergoing or had completed immunosuppressive cancer therapy (Open Forum Infect Dis 2017;4(suppl_1):S415). The authors concluded that RZV produced robust humoral and CMI in these patients excluding non-Hodgkin B-cell lymphoma or CLL. This has been published only in abstract form at this time.
In another recent publication, the RZV was studied in a phase I/II randomized, placebo-controlled trial of people with hematologic malignancies who had previously undergone autologous hematopoietic stem cell transplantation 50-70 days earlier. This study observed strong and persistent humoral and CMI responses to the vaccine (Blood 2014;124:2921-2929).
RZV has been shown to be safe, more effective, and cost-effective in immunocompetent people over 50 years old. Although more study is needed for RZV in immunocompromised patients, it may prove to be helpful in lowering the burden of HZ disease.
LISA LOHR, PHARMD, BCPS, BCOP, is Clinical Oncology Specialist/MTM provider at Masonic Cancer Clinic Fairview/University of Minnesota Health, Minneapolis.
For Further Reading
* Cunningham AL, Lal H, Kovac M, et al. Efficacy of the herpes zoster subunit vaccine in adults 70 years of age and older. N Engl J Med 2016;375:1019-1032.
* Dooling KL, Guo A, Patel M, et al. Recommendations of the Advisory Committee on Immunization Practices the use of Herpes Zoster Vaccines. MMWR Morb Mortal Wkly Rep 2018;67:103-108.
* John AR, Canaday DH. Herpes zoster in the older adult. Inf Dis Clin N Am 2017;31:811-826.
* Lal H, Cunningham AL, Godeaux O, et al. Efficacy of an adjuvanted herpes zoster subunit vaccine in older adults. N Engl J Med 2015;372:2087-2096.
* Le P, Rothberg MB. Cost-effectiveness of the adjuvanted herpes zoster subunit vaccine in older adults. JAMA Intern Med 2018; doi:10.1001/jamainternmed.2017.7431.
* Van Epps P, Schmader KE, Canaday DH. Herpes zoster vaccination: controversies and common clinical questions. Gerontology 2016;62:150-154.