Use of RZV in Immunocompromised Adults Aged >19 Years

Abstract and Introduction

Introduction

Zoster Vaccine Recombinant, Adjuvanted (Shingrix, GlaxoSmithKline [GSK]) is a 2-dose (0.5 mL each) subunit vaccine containing recombinant glycoprotein E in combination with adjuvant (AS01_B) that was licensed in the United States for prevention of herpes zoster for adults aged ≥50 years by the Food and Drug Administration (FDA) and recommended for immunocompetent adults aged ≥50 years by the Advisory Committee on Immunization Practices (ACIP) in 2017*.^[1] On July 23, 2021, the FDA expanded the indication for recombinant zoster vaccine (RZV) to include adults aged ≥18 years who are or will be at increased risk for herpes zoster because of immunodeficiency or immunosuppression caused by known disease or therapy.^[2] On October 20, 2021, ACIP recommended 2 doses of RZV for the prevention of herpes zoster and related complications in adults aged ≥19 years^† who are or will be immunodeficient or immunosuppressed because of disease or therapy. RZV is the first herpes zoster vaccine approved for use in immunocompromised persons. With moderate to high vaccine efficacy and an acceptable safety profile, RZV has the potential to prevent considerable herpes zoster incidence and related complications. This report updates previous ACIP recommendations for the prevention of herpes zoster.^[1,3]

Herpes zoster is a painful, cutaneous eruption, usually involving one to three adjacent dermatomes,^§ resulting from reactivation of latent varicella-zoster virus. The incidence of herpes zoster and related complications (including the most common complication of postherpetic neuralgia) increase with age.^[3–5] The risk for herpes zoster and related complications is generally higher in immunocompromised compared with immunocompetent adults, although there is heterogeneity within and across immunocompromised groups.^[6,7] The risk for herpes zoster among younger adults with certain immunocompromising conditions can be comparable to or higher than that in the general adult population aged >50 years.^[6,7] Because immunosuppression and immunodeficiency were contraindications for the previously available vaccine, zoster vaccine live,^¶ and RZV was originally recommended for immunocompetent adults aged ≥50 years, there has been an unmet need for vaccination against herpes zoster in immunocompromised adults.

During December 2017–October 2021, the ACIP Herpes Zoster Work Group participated in monthly or bimonthly teleconferences to review herpes zoster epidemiology and evidence for the efficacy and safety of RZV in immunocompromised adults. These topics were discussed during four ACIP meetings in 2021. To guide its deliberations, ACIP used the Evidence to Recommendations Framework and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach^[8] to evaluate possible benefits (prevention of herpes zoster, postherpetic neuralgia, and herpes zoster-related hospitalizations) and harms (serious adverse events [SAEs],** immune-mediated disease, graft-versus-host-disease, graft rejection, and reactogenicity) associated with RZV.^††

Prevention of herpes zoster and occurrence of SAEs were deemed critical outcomes by the work group. Five studies in four immunocompromised groups^§§ evaluated herpes zoster as an outcome.^[9–13] Estimates of vaccine efficacy (VE) came from three studies, with VE of 68.2% (95% CI = 55.6%–77.5%) for autologous hematopoietic cell transplant recipients,^[11] and 87.2% (44.3%–98.6%) and 90.5% (73.5%–97.5%) in post hoc efficacy analyses for patients with hematologic malignancies^[12] and potential immune-mediated diseases,^[13] respectively. SAEs were evaluated in seven studies^[9–15] in six immunocompromised groups (2,541 RZV recipients).^¶¶ Overall, rates of SAEs were comparable between RZV and placebo recipients (risk ratios ranged from 0.79 to 1.99). SAEs deemed to be related to vaccination by study investigators ranged from 0% to 1.6% in the RZV group and 0% to 0.76% in the placebo group. The level of certainty for prevention of herpes zoster and occurrence of SAEs was type 2 (moderate).***

In addition to the critical outcomes (prevention of herpes zoster and SAEs), the remaining outcomes were deemed important by the work group. One study among hematopoietic cell transplant recipients^[11] reported VE of 89% (95% CI = 22%–100%) for prevention of postherpetic neuralgia and 85% (32%–97%) for prevention of herpes zoster-related hospitalization (certainty type 3 [low]). Immune-mediated diseases were evaluated in six studies^[9,11–15] in five immunocompromised groups^††† and were not increased among RZV recipients (certainty type 4 [very low]). One study in patients with hematologic malignancies^[12] reported on graft-versus-host-disease among hematopoietic cell transplant recipients and did not identify an increased risk among RZV recipients (certainty type 4 [very low]). One study among renal transplant patients^[15] reported on graft rejection and did not identify an increased risk among RZV recipients (certainty type 3). Local and systemic grade 3 reactions^§§§ were evaluated in six studies^{[9–12,14,15]} in five immunocompromised groups.^¶¶¶ Local grade 3 reactions occurred in 10.7% to 14.2% of RZV recipients, and systemic grade 3 reactions occurred in 9.9% to 22.3% of RZV recipients, compared with 0% to 0.3% and 6.0% to 15.5%, respectively, among placebo recipients (certainty type 2).

Additional data reviewed within the Evidence to Recommendations Framework supported the use of RZV in immunocompromised adults.**** Two economic studies assessed RZV use (versus no vaccination) among immunocompromised adults.^[16] Both studies focused on hematopoietic cell transplant patients as the base case and found that vaccination was cost-saving, and eight to 10 persons receiving complete vaccination were needed to avert an episode of herpes zoster. Additional analyses assessed vaccination among persons with other immunocompromising conditions^†††† and found that vaccination would cost <$99,000 per quality-adjusted life-year gained for most scenarios and could be cost-saving in several scenarios. Vaccination among patients with autoimmune and inflammatory conditions yielded the highest estimate of $208,000 per quality-adjusted life-year gained. Variations in results across scenarios were likely due to differences in estimated costs of health care, VE, and incidence of herpes zoster across different immunocompromising conditions.

Overall, the work group determined that herpes zoster in immunocompromised adults is of public health importance; the desirable anticipated effects of RZV in immunocompromised adults are large and the undesirable effects are small, which favors the intervention; immunocompromised adults probably feel that the desirable effects of vaccination with RZV are large relative to the undesirable effects and that there is probably not important uncertainty or variability in how patients value these outcomes. Use of RZV in immunocompromised adults is acceptable to stakeholders and a reasonable and efficient allocation of resources; health equity would probably be increased; and the intervention would be feasible to implement. On October 20, 2021, with this input from the work group, ACIP unanimously approved the recommendation.

With moderate to high VE among several immunocompromised groups and an acceptable safety profile across a range of immunocompromised groups, RZV has the potential to prevent considerable herpes zoster incidence and related complications. Recommending vaccination of immunocompromised adults aged ≥19 years will enable providers to vaccinate patients at a time most appropriate for their immunocompromising condition or therapy.